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Direct-to-Consumer Testing’s Expansion to Rheumatology Has Benefits but Potential Risks
When Jennifer Welsh, a 40-year-old from New Britain, Connecticut, visited her doctor about pain in her joints and neck, her doctor sent her to the emergency department (ED) to rule out meningitis. The ED did rule that out, as well as strep, so Ms. Welsh went to her follow-up appointment a few days later, hoping for answers or at least more tests to get those answers.
Instead, the doctor — a different one from the same practice as her primary care physician (PCP) — wouldn’t even talk to Ms. Welsh about her symptoms because she couldn’t see the ED’s results and refused to view the results that Ms. Welsh could pull up online.
“She just completely shut me down,” Ms. Welsh recalled. “It was a really awful appointment, and I left in tears. I was in physical pain, I had just been to the ER, nothing is really resolved, I’m stressed out about it, and this woman is completely dismissing me.”
She had been able to schedule an appointment with her regular PCP later that week, but after the harrowing experience with this doctor, she wondered if her PCP would order the rheumatoid arthritis (RA) test that Ms. Welsh suspected she needed. So, she took matters into her own hands.
“I was searching for what test to ask for from my doctor,” she said, and she found that she could order it on her own from a major lab company she was already familiar with. For around $100, “I could get it done and see what it says on my own,” she said.
But that’s not how it worked out. Her regular PCP apologized for the other doctor’s behavior and ordered the RA test as well as additional tests — and got results while Ms. Welsh still waited for the one she ordered to arrive over a week later.
At first, Ms. Welsh was grateful she could order the RA test without her doctor’s referral. “I felt it gave me a sense of control over the situation that I felt really not in control of, until the system failed me, and I didn’t get the results,” she said. But then, “not having someone I could call and get an answer about why my tests were delayed, why I wasn’t able to access them, why it was taking so long — it was definitely anxiety-inducing.”
A Growing Market
Ms. Welsh is one of a growing number of patients who are ordering direct-to-consumer (DTC) lab tests without the recommendation or guidance of a doctor. They’re offered online by labs ranging from well-established giants like Quest and Labcorp to smaller, potentially less vetted companies, although some smaller companies contract with larger companies like Quest. Combined, the DTC market is projected to be worth $2 billion by 2025.
Yet the burgeoning industry has also drawn critiques from both bioethicists and privacy experts. A research letter in JAMA in 2023, for example, found that less than half of the 21 companies identified in an online search declared Health Insurance Portability and Accountability Act compliance, while more than half “indicated the potential use of consumer data for research purposes either internally or through third-party sharing.” That study found the most commonly offered tests were related to diabetes, the thyroid, and vitamin levels, and hormone tests for men and women, such as testosterone or estradiol.
But a number of companies also offer tests related to rheumatologic conditions. A handful of tests offered by Labcorp, for example, could be used in rheumatology, such as tests for celiac antibodies or high-sensitivity C-reactive protein. Quest similarly offers a handful of autoimmune-related tests. But other companies offer a long slate of autoimmune or antibody tests.
The antinuclear antibody (ANA) test and RA panel offered by Quest are the same tests, run and analyzed in the same labs, as those ordered by physicians and hospitals, according to James Faix, MD, the medical director of immunology at Quest Diagnostics. Their RA panel includes rheumatoid factor and anti-cyclic citrullinated peptide as well as antibody to mutated citrullinated vimentin, “which may detect approximately 10%-15%” of patients who test negative to the first two.
Quest’s ANA test with reflex costs $112, and its RA panel costs $110, price points that are similar across other companies’ offerings. Labcorp declined to respond to questions about its DTC tests, and several smaller companies did not respond to queries about their offerings. It can therefore be hard to assess what’s included or what the quality is of many DTC tests, particularly from smaller, less established companies.
Oversight and Quality Control
Anthony Killeen, MD, PhD, president of the Association for Diagnostics & Laboratory Medicine (ADLM) and director of Clinical Laboratories at the University of Minnesota Medical Center in Minneapolis, said via email that the ADLM supports “expanding consumer access to direct-to-consumer laboratory testing services that have demonstrated analytical and clinical validity and clinical utility,” given the importance of individuals learning about their health status and becoming more involved in health decisions. But the ADLM also recommends “that only CLIA-certified laboratories perform direct-to-consumer testing,” he said.
“There are direct-to-consumer tests on the market that are not medical-grade laboratory tests and that may be performed in nonaccredited laboratories,” Dr. Killeen said. “We advise consumers to steer clear of such tests.” The ADLM also encourages consumers to “work with qualified healthcare providers when making decisions based off the results they receive from any direct-to-consumer tests” and recommends that DTC test companies “provide consumers with sufficient information and/or access to expert help to assist them in ordering tests and interpreting the results.”
Yet it’s unclear how much support, if any, consumers can receive in terms of understanding what their tests mean. Most of the companies in the 2023 study offered optional follow-up with a healthcare professional, but these professionals ranged from physicians to “health coaches,” and all the companies had disclaimers that “test results did not constitute medical advice.”
At Quest, the only company to respond to this news organization’s request for comment, consumer-initiated tests ordered online are first reviewed by a physician at PWNHealth, an independent, third-party physician network, to determine that it’s appropriate before the lab order is actually placed.
“Once results are available, individuals have the option to discuss their results with an independent physician at no extra cost,” Dr. Faix said. ANA or RA results outside the normal ranges may trigger a “call from a PWNHealth healthcare coordinator, who can help provide information, suggestions on next steps, and set up time for the individual to speak with an independent physician to discuss questions or concerns regarding the results,” he said.
“Our goal is not to replace the role of a healthcare provider,” Dr. Faix said. “We are providing an alternate way for people to engage with the healthcare system that offers convenience, gives people more control over their own healthcare journeys, and meets them where they are, supporting both consumers and their care teams.” The company has expanded its offerings from an initial 30 tests made available in 2018 to over 130 today, deciding which to offer “based on consumer research and expertise of clinical experts.” The company has also “seen steady interest in our two consumer rheumatology offerings,” Dr. Faix said.
The DTC Landscape in Rheumatology
Within rheumatology, among the most popular tests is for ANA, based on the experience of Alfred Kim, MD, PhD, associate professor of medicine at Washington University School of Medicine in St Louis, Missouri.
“For a lot of people, losing control over their health is maybe the most frightening experience they can have, so I think a lot of patients use this as a way to kind of have ownership over their health,” Dr. Kim said. “Let’s say they’ve been to four doctors. No one can explain what’s going on. They’re getting frustrated, and so they just turn to solutions where they feel like they have ownership over the situation.”
Though the market is undoubtedly growing, the growth appears uneven across geography and institution types. Kim has seen a “fair number of referrals,” with patients coming in with results from a DTC test. Michael Putman, MD, MSci, assistant professor of medicine at the Medical College of Wisconsin in Milwaukee, hasn’t seen it much. “I know that patients can get testing done themselves independently, but I don’t have people routinely coming in with tests they’ve ordered in advance of our appointment,” Dr. Putman said, but, like Dr. Kim, he recognizes why patients might seek them out.
“I’m a big fan of patient empowerment, and I do think that medicine serves a gatekeeper role that sometimes can be a little too far,” Dr. Putman said. “I think there is value to patients being able to get more information and try to understand what is happening in their bodies. I have a lot of compassion for someone who would try to find testing outside of the normal channels.”
Indeed, bringing these test results to a visit could be informative in some scenarios. A negative ANA test, for example, pretty much excludes lupus 100%, Dr. Kim said. But a positive ANA doesn’t tell him much, and if his clinical suspicion for a condition is high, he likely would order that test anyway, even if the patient came in with their own results. Dr. Putman also pointed out that the vast majority of tests used in rheumatology have a high rate of false positives.
“I think that will be the major area where this causes quite a lot of grief to patients and some frustration to some providers,” he said. A rheumatoid factor test like the one Ms. Welsh ordered, for example, might test positive in 10 out of 100 people randomly gathered in a room, but the majority of those individuals would not have RA, he said.
That test is another popular rheumatology one, according to Timothy Niewold, MD, vice chair for research in the Hospital for Special Surgery Department of Medicine in New York City. Among the possible reasons people might order these tests are the delay in diagnosis that can often occur with a lot of rheumatologic conditions and that “it can take a while to see a rheumatologist, depending on what part of the country you’re in and what the availability is,” he said. He’s not surprised to see tests for Sjögren disease among the offerings, for example, because it’s a condition that’s difficult to diagnose but reasonably common within autoimmune diseases.
Risks vs Benefits
DTC testing is not an answer to the national shortage of rheumatologists, however, especially given the risks that Dr. Niewold, Dr. Putman, and Dr. Kim worry outweigh potential benefits. On the one hand, getting online test results may help expedite a referral to a specialist, Dr. Niewold said. But a long wait for that appointment could then easily become a bigger source of anxiety than comfort, Dr. Putman said.
“It’s a trade-off where you are accepting a lot more people getting false-positive diagnoses and spending months thinking they have some disease where they might not, in exchange for a couple people who would have had a delayed diagnosis,” Dr. Putman said. “There’s an enormous amount of existential suffering,” that’s familiar to rheumatologists because some patients may dread the diagnosis of a rheumatic disease the way they might fear a cancer diagnosis, especially if they have lost a family member to a condition that they suspect they share, he said. “To put yourself into an existential catastrophe — that’s not a small harm.”
Dr. Niewold agreed, pointing out that patients with a positive ANA test may “get unnecessarily worried and stay up all night reading about lupus, getting scared for weeks on end before seeing a specialist.” And there are financial harms as well for patients who may order the same test multiple times, or a whole slate of tests, that they don’t need for hundreds or thousands of dollars. There’s also the lost time and effort of researching a condition or even seeking out support groups that patients may pursue, Dr. Niewold said.
The likely biggest risk to individuals, however, is the potential for overdiagnosis or misdiagnosis.
“If someone comes in and they’ve read the textbook on lupus and they have a positive ANA, it’s really hard as a rheumatologist to walk that back,” Dr. Putman said. “The human mind is a powerful thing,” he added, and people who get a positive test will likely start to notice things like joint pain or a rash on their cheeks and begin attributing it to a diagnosis they risk convincing themselves they have. “When people come into your clinic not knowing what a disease would look like and they just tell you how they’re feeling, it’s a much cleaner and more honest way to approach diagnosis.”
Most patients likely don’t realize, for example, that none of the tests rheumatologists usually order are diagnostic in and of themselves, Dr. Niewold said. “They’re all kind of like stars in the constellation of a diagnosis,” he said. “They’re helpful, but none of them is sufficient by itself.”
Dr. Killeen agreed, noting that “consumers might not understand the nuances of these tests well enough to know whether it is appropriate to order them or how to interpret the results correctly.” Given the long-term implications of a diagnosis for a rheumatologic disease, “I would have concerns about consumers ordering and interpreting rheumatologic tests without working closely with their physicians,” Dr. Killeen said. “The main concern that lab experts have about direct-to-consumer tests is the potential for people to get misleading results and/or to misinterpret their results, which in turn could lead to people not getting the treatment they need or getting treatment when they don’t need any at all.”
It’s one thing for patients to come in asking for a particular treatment they may not need but which a doctor may be able to dissuade them from seeking. But Dr. Kim also pointed out the risk that patients may decide to treat themselves with therapies that haven’t undergone rigorous testing or haven’t been recommended by a physician.
“We tend to have people who come in with a pretty clear idea of what they want done, but the problem is, we don’t know if their reasoning is correct from a clinical perspective,” Dr. Kim said. Companies offer these tests with the belief that they’re “providing patients a choice, an option to take ownership,” he said, “but the potential harm can be realized very quickly because there are going to be people who are misdiagnosing themselves and, worse yet, may then pursue their own treatment plan that’s going in the opposite direction of where we think it needs to go.”
Or, on the flip side, if a patient erroneously believes they have the answer to what ails them, it may delay diagnosis of a more serious condition that’s rarer or harder to detect. Kim pointed to, for example, intravascular lymphoma, which is notoriously as difficult to identify as it is rare and aggressive. If a patient’s confirmation bias has led them to believe they have an autoimmune condition, they may not receive the more serious diagnosis until it’s advanced too far to treat.
Patient-Provider Relationship Friction
Another concern is how these tests may lead to confusion and frustration that can erode the patient-provider relationship, particularly because most patients don’t know how to interpret the results or understand the bigger context in which the results have to be interpreted. Many patients may think a test can come back with a binary answer, a positive or negative, and that means they do or don’t have a condition. That’s generally true for pregnancy tests, COVID tests, and sexually transmitted infection tests — the kinds of tests that have long been available to consumers and which have fairly straightforward answers.
But physicians know that’s not the case for many conditions, particularly those in rheumatology.
“In rheumatic diseases, because the tests have such marginal value in terms of diagnosis, almost always we develop a suspicion before we even think about ordering the tests, and then that dictates whether or not we cross that threshold,” Dr. Kim said. “A negative test doesn’t exclude the fact that you may have disease X, but a positive test also doesn’t mean you have disease X. All they provide is an idea of the risk.”
But some patients who come in with DTC test results have “already made the decision in their mind that they have a certain condition,” Dr. Kim said. “This is obviously dangerous because the majority of these patients do not have the condition they think they have, and it leaves a very uncomfortable feeling after the visit because they feel like they’ve been either betrayed by me or by the test, and they leave more confused.”
Patients may also come in with tests that a doctor isn’t familiar with or isn’t sure how to interpret on its own, at least for that particular patient.
“For ANA testing, we have a pretty good idea of its positive and negative predictive value because it’s ordered so much, but for many of these tests being offered, there are specific autoantibodies, and we tend to only get them in people where there’s a clinical suspicion,” Dr. Kim said. “Within that very specific context, we kind of understand what that value means, but if you give it to the general public, then those numbers aren’t as applicable and most likely overestimate the risk of disease.”
Even if providers consider the results of a DTC test in their differential, they may want to be sure it’s from a trustworthy source. “If a provider is uncertain about whether a direct-to-consumer testing company is reputable or about whether a direct-to-consumer test result is reliable, I would encourage them to consult with their laboratory medicine colleagues,” Dr. Killeen said.
Responding to Patients
Like any other patient coming to a clinical visit, the most common reason patients are likely ordering these tests is that they’re seeking answers. Kim doesn’t typically see patients doing their own monitoring for diagnosed conditions between visits — the expense would add up too quickly — or testing for genetic markers, which likely wouldn’t be very helpful either.
“Even though most of our diseases probably have a genetic underpinning, how much it contributes is always unclear,” Dr. Kim said. Even conditions with clear genetic variants, such as familial Mediterranean fever, spondyloarthritis, and Behçet disease, can only support a diagnosis, not diagnose it on its own, Dr. Killeen said. And these are not among the tests currently available on most DTC company sites.
While there are also tests that can offer information about genetic risks for certain medications, such as a thiopurine methyltransferase test to find out if a patient lacks the enzyme needed to break down the immunosuppressant drug azathioprine, Kim hasn’t seen patients seeking these out either.
“The more global and more compassionate way to think about this is that we have a lot of people who are struggling to understand what’s going on with their bodies, and most physicians really don’t know what the next steps are for these people,” Dr. Kim said. “They’re desperate, and their quality of life is so poor that they’re going to take extreme steps to try to manage their own frustration with this condition.”
That means clinicians’ most powerful tools when patients come in with DTC test results are their listening skills.
“Empathy is the most important thing, just being able to share the patient’s frustration to the point where they had to take matters into their own hands,” Dr. Kim said. “I think a lot of rheumatologists are actually pretty comfortable being in this position.”
Additionally, doctors should know that some patients may be engaging in attempts to self-diagnose, self-treat, or otherwise self-manage their symptoms or perceived condition. “They just need to be aware and try to make sure there’s no harm being done,” Dr. Kim said.
Ms. Welsh didn’t seek treatment or diagnosis on her own, but getting her test also did not give her the control she was seeking. “Looking back, it was kind of a waste of money, but it felt good in the moment,” Ms. Welsh said. “I was so upset, and I wanted that control, and in the end, it didn’t get me results any sooner, and it didn’t give me peace of mind.”
It was Ms. Welsh’s primary care doctor listening to her concerns, ordering the same test she had ordered with several others, and working with her to seek answers that reassured her that her provider cared about her well-being.
“A lot of what I do in my business is reassure people that you know what they have is treatable or not going to end their life as they know it,” Dr. Putman said. “And you certainly can’t reassure them if they’re not in your clinic yet.”
Dr. Putman has participated in clinical trials with AbbVie, consulting with Novartis and GSK, and clinical trials and consulting with Amgen and AstraZeneca. Dr. Niewold reported receiving research grants from EMD Serono and Zenas BioPharma and consulting for Thermo Fisher Scientific, Progentec Diagnostics, Roivant Sciences, AstraZeneca, S3 Connected Health, Flagship Pioneering, and Guidepoint. Dr. Kim reported sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, Novartis, and CRISPR Therapeutics; royalties from Kypha; and consulting/speaking for Amgen, ANI Pharmaceuticals, Atara Biotherapeutics, Aurinia Pharmaceuticals, CARGO Therapeutics, Exagen Diagnostics, GSK, Hinge Bio, Kypha, Progentec Diagnostics, Synthekine, and UpToDate. Dr. Killeen had no relevant financial relationships to disclose.
A version of this article first appeared on Medscape.com.
When Jennifer Welsh, a 40-year-old from New Britain, Connecticut, visited her doctor about pain in her joints and neck, her doctor sent her to the emergency department (ED) to rule out meningitis. The ED did rule that out, as well as strep, so Ms. Welsh went to her follow-up appointment a few days later, hoping for answers or at least more tests to get those answers.
Instead, the doctor — a different one from the same practice as her primary care physician (PCP) — wouldn’t even talk to Ms. Welsh about her symptoms because she couldn’t see the ED’s results and refused to view the results that Ms. Welsh could pull up online.
“She just completely shut me down,” Ms. Welsh recalled. “It was a really awful appointment, and I left in tears. I was in physical pain, I had just been to the ER, nothing is really resolved, I’m stressed out about it, and this woman is completely dismissing me.”
She had been able to schedule an appointment with her regular PCP later that week, but after the harrowing experience with this doctor, she wondered if her PCP would order the rheumatoid arthritis (RA) test that Ms. Welsh suspected she needed. So, she took matters into her own hands.
“I was searching for what test to ask for from my doctor,” she said, and she found that she could order it on her own from a major lab company she was already familiar with. For around $100, “I could get it done and see what it says on my own,” she said.
But that’s not how it worked out. Her regular PCP apologized for the other doctor’s behavior and ordered the RA test as well as additional tests — and got results while Ms. Welsh still waited for the one she ordered to arrive over a week later.
At first, Ms. Welsh was grateful she could order the RA test without her doctor’s referral. “I felt it gave me a sense of control over the situation that I felt really not in control of, until the system failed me, and I didn’t get the results,” she said. But then, “not having someone I could call and get an answer about why my tests were delayed, why I wasn’t able to access them, why it was taking so long — it was definitely anxiety-inducing.”
A Growing Market
Ms. Welsh is one of a growing number of patients who are ordering direct-to-consumer (DTC) lab tests without the recommendation or guidance of a doctor. They’re offered online by labs ranging from well-established giants like Quest and Labcorp to smaller, potentially less vetted companies, although some smaller companies contract with larger companies like Quest. Combined, the DTC market is projected to be worth $2 billion by 2025.
Yet the burgeoning industry has also drawn critiques from both bioethicists and privacy experts. A research letter in JAMA in 2023, for example, found that less than half of the 21 companies identified in an online search declared Health Insurance Portability and Accountability Act compliance, while more than half “indicated the potential use of consumer data for research purposes either internally or through third-party sharing.” That study found the most commonly offered tests were related to diabetes, the thyroid, and vitamin levels, and hormone tests for men and women, such as testosterone or estradiol.
But a number of companies also offer tests related to rheumatologic conditions. A handful of tests offered by Labcorp, for example, could be used in rheumatology, such as tests for celiac antibodies or high-sensitivity C-reactive protein. Quest similarly offers a handful of autoimmune-related tests. But other companies offer a long slate of autoimmune or antibody tests.
The antinuclear antibody (ANA) test and RA panel offered by Quest are the same tests, run and analyzed in the same labs, as those ordered by physicians and hospitals, according to James Faix, MD, the medical director of immunology at Quest Diagnostics. Their RA panel includes rheumatoid factor and anti-cyclic citrullinated peptide as well as antibody to mutated citrullinated vimentin, “which may detect approximately 10%-15%” of patients who test negative to the first two.
Quest’s ANA test with reflex costs $112, and its RA panel costs $110, price points that are similar across other companies’ offerings. Labcorp declined to respond to questions about its DTC tests, and several smaller companies did not respond to queries about their offerings. It can therefore be hard to assess what’s included or what the quality is of many DTC tests, particularly from smaller, less established companies.
Oversight and Quality Control
Anthony Killeen, MD, PhD, president of the Association for Diagnostics & Laboratory Medicine (ADLM) and director of Clinical Laboratories at the University of Minnesota Medical Center in Minneapolis, said via email that the ADLM supports “expanding consumer access to direct-to-consumer laboratory testing services that have demonstrated analytical and clinical validity and clinical utility,” given the importance of individuals learning about their health status and becoming more involved in health decisions. But the ADLM also recommends “that only CLIA-certified laboratories perform direct-to-consumer testing,” he said.
“There are direct-to-consumer tests on the market that are not medical-grade laboratory tests and that may be performed in nonaccredited laboratories,” Dr. Killeen said. “We advise consumers to steer clear of such tests.” The ADLM also encourages consumers to “work with qualified healthcare providers when making decisions based off the results they receive from any direct-to-consumer tests” and recommends that DTC test companies “provide consumers with sufficient information and/or access to expert help to assist them in ordering tests and interpreting the results.”
Yet it’s unclear how much support, if any, consumers can receive in terms of understanding what their tests mean. Most of the companies in the 2023 study offered optional follow-up with a healthcare professional, but these professionals ranged from physicians to “health coaches,” and all the companies had disclaimers that “test results did not constitute medical advice.”
At Quest, the only company to respond to this news organization’s request for comment, consumer-initiated tests ordered online are first reviewed by a physician at PWNHealth, an independent, third-party physician network, to determine that it’s appropriate before the lab order is actually placed.
“Once results are available, individuals have the option to discuss their results with an independent physician at no extra cost,” Dr. Faix said. ANA or RA results outside the normal ranges may trigger a “call from a PWNHealth healthcare coordinator, who can help provide information, suggestions on next steps, and set up time for the individual to speak with an independent physician to discuss questions or concerns regarding the results,” he said.
“Our goal is not to replace the role of a healthcare provider,” Dr. Faix said. “We are providing an alternate way for people to engage with the healthcare system that offers convenience, gives people more control over their own healthcare journeys, and meets them where they are, supporting both consumers and their care teams.” The company has expanded its offerings from an initial 30 tests made available in 2018 to over 130 today, deciding which to offer “based on consumer research and expertise of clinical experts.” The company has also “seen steady interest in our two consumer rheumatology offerings,” Dr. Faix said.
The DTC Landscape in Rheumatology
Within rheumatology, among the most popular tests is for ANA, based on the experience of Alfred Kim, MD, PhD, associate professor of medicine at Washington University School of Medicine in St Louis, Missouri.
“For a lot of people, losing control over their health is maybe the most frightening experience they can have, so I think a lot of patients use this as a way to kind of have ownership over their health,” Dr. Kim said. “Let’s say they’ve been to four doctors. No one can explain what’s going on. They’re getting frustrated, and so they just turn to solutions where they feel like they have ownership over the situation.”
Though the market is undoubtedly growing, the growth appears uneven across geography and institution types. Kim has seen a “fair number of referrals,” with patients coming in with results from a DTC test. Michael Putman, MD, MSci, assistant professor of medicine at the Medical College of Wisconsin in Milwaukee, hasn’t seen it much. “I know that patients can get testing done themselves independently, but I don’t have people routinely coming in with tests they’ve ordered in advance of our appointment,” Dr. Putman said, but, like Dr. Kim, he recognizes why patients might seek them out.
“I’m a big fan of patient empowerment, and I do think that medicine serves a gatekeeper role that sometimes can be a little too far,” Dr. Putman said. “I think there is value to patients being able to get more information and try to understand what is happening in their bodies. I have a lot of compassion for someone who would try to find testing outside of the normal channels.”
Indeed, bringing these test results to a visit could be informative in some scenarios. A negative ANA test, for example, pretty much excludes lupus 100%, Dr. Kim said. But a positive ANA doesn’t tell him much, and if his clinical suspicion for a condition is high, he likely would order that test anyway, even if the patient came in with their own results. Dr. Putman also pointed out that the vast majority of tests used in rheumatology have a high rate of false positives.
“I think that will be the major area where this causes quite a lot of grief to patients and some frustration to some providers,” he said. A rheumatoid factor test like the one Ms. Welsh ordered, for example, might test positive in 10 out of 100 people randomly gathered in a room, but the majority of those individuals would not have RA, he said.
That test is another popular rheumatology one, according to Timothy Niewold, MD, vice chair for research in the Hospital for Special Surgery Department of Medicine in New York City. Among the possible reasons people might order these tests are the delay in diagnosis that can often occur with a lot of rheumatologic conditions and that “it can take a while to see a rheumatologist, depending on what part of the country you’re in and what the availability is,” he said. He’s not surprised to see tests for Sjögren disease among the offerings, for example, because it’s a condition that’s difficult to diagnose but reasonably common within autoimmune diseases.
Risks vs Benefits
DTC testing is not an answer to the national shortage of rheumatologists, however, especially given the risks that Dr. Niewold, Dr. Putman, and Dr. Kim worry outweigh potential benefits. On the one hand, getting online test results may help expedite a referral to a specialist, Dr. Niewold said. But a long wait for that appointment could then easily become a bigger source of anxiety than comfort, Dr. Putman said.
“It’s a trade-off where you are accepting a lot more people getting false-positive diagnoses and spending months thinking they have some disease where they might not, in exchange for a couple people who would have had a delayed diagnosis,” Dr. Putman said. “There’s an enormous amount of existential suffering,” that’s familiar to rheumatologists because some patients may dread the diagnosis of a rheumatic disease the way they might fear a cancer diagnosis, especially if they have lost a family member to a condition that they suspect they share, he said. “To put yourself into an existential catastrophe — that’s not a small harm.”
Dr. Niewold agreed, pointing out that patients with a positive ANA test may “get unnecessarily worried and stay up all night reading about lupus, getting scared for weeks on end before seeing a specialist.” And there are financial harms as well for patients who may order the same test multiple times, or a whole slate of tests, that they don’t need for hundreds or thousands of dollars. There’s also the lost time and effort of researching a condition or even seeking out support groups that patients may pursue, Dr. Niewold said.
The likely biggest risk to individuals, however, is the potential for overdiagnosis or misdiagnosis.
“If someone comes in and they’ve read the textbook on lupus and they have a positive ANA, it’s really hard as a rheumatologist to walk that back,” Dr. Putman said. “The human mind is a powerful thing,” he added, and people who get a positive test will likely start to notice things like joint pain or a rash on their cheeks and begin attributing it to a diagnosis they risk convincing themselves they have. “When people come into your clinic not knowing what a disease would look like and they just tell you how they’re feeling, it’s a much cleaner and more honest way to approach diagnosis.”
Most patients likely don’t realize, for example, that none of the tests rheumatologists usually order are diagnostic in and of themselves, Dr. Niewold said. “They’re all kind of like stars in the constellation of a diagnosis,” he said. “They’re helpful, but none of them is sufficient by itself.”
Dr. Killeen agreed, noting that “consumers might not understand the nuances of these tests well enough to know whether it is appropriate to order them or how to interpret the results correctly.” Given the long-term implications of a diagnosis for a rheumatologic disease, “I would have concerns about consumers ordering and interpreting rheumatologic tests without working closely with their physicians,” Dr. Killeen said. “The main concern that lab experts have about direct-to-consumer tests is the potential for people to get misleading results and/or to misinterpret their results, which in turn could lead to people not getting the treatment they need or getting treatment when they don’t need any at all.”
It’s one thing for patients to come in asking for a particular treatment they may not need but which a doctor may be able to dissuade them from seeking. But Dr. Kim also pointed out the risk that patients may decide to treat themselves with therapies that haven’t undergone rigorous testing or haven’t been recommended by a physician.
“We tend to have people who come in with a pretty clear idea of what they want done, but the problem is, we don’t know if their reasoning is correct from a clinical perspective,” Dr. Kim said. Companies offer these tests with the belief that they’re “providing patients a choice, an option to take ownership,” he said, “but the potential harm can be realized very quickly because there are going to be people who are misdiagnosing themselves and, worse yet, may then pursue their own treatment plan that’s going in the opposite direction of where we think it needs to go.”
Or, on the flip side, if a patient erroneously believes they have the answer to what ails them, it may delay diagnosis of a more serious condition that’s rarer or harder to detect. Kim pointed to, for example, intravascular lymphoma, which is notoriously as difficult to identify as it is rare and aggressive. If a patient’s confirmation bias has led them to believe they have an autoimmune condition, they may not receive the more serious diagnosis until it’s advanced too far to treat.
Patient-Provider Relationship Friction
Another concern is how these tests may lead to confusion and frustration that can erode the patient-provider relationship, particularly because most patients don’t know how to interpret the results or understand the bigger context in which the results have to be interpreted. Many patients may think a test can come back with a binary answer, a positive or negative, and that means they do or don’t have a condition. That’s generally true for pregnancy tests, COVID tests, and sexually transmitted infection tests — the kinds of tests that have long been available to consumers and which have fairly straightforward answers.
But physicians know that’s not the case for many conditions, particularly those in rheumatology.
“In rheumatic diseases, because the tests have such marginal value in terms of diagnosis, almost always we develop a suspicion before we even think about ordering the tests, and then that dictates whether or not we cross that threshold,” Dr. Kim said. “A negative test doesn’t exclude the fact that you may have disease X, but a positive test also doesn’t mean you have disease X. All they provide is an idea of the risk.”
But some patients who come in with DTC test results have “already made the decision in their mind that they have a certain condition,” Dr. Kim said. “This is obviously dangerous because the majority of these patients do not have the condition they think they have, and it leaves a very uncomfortable feeling after the visit because they feel like they’ve been either betrayed by me or by the test, and they leave more confused.”
Patients may also come in with tests that a doctor isn’t familiar with or isn’t sure how to interpret on its own, at least for that particular patient.
“For ANA testing, we have a pretty good idea of its positive and negative predictive value because it’s ordered so much, but for many of these tests being offered, there are specific autoantibodies, and we tend to only get them in people where there’s a clinical suspicion,” Dr. Kim said. “Within that very specific context, we kind of understand what that value means, but if you give it to the general public, then those numbers aren’t as applicable and most likely overestimate the risk of disease.”
Even if providers consider the results of a DTC test in their differential, they may want to be sure it’s from a trustworthy source. “If a provider is uncertain about whether a direct-to-consumer testing company is reputable or about whether a direct-to-consumer test result is reliable, I would encourage them to consult with their laboratory medicine colleagues,” Dr. Killeen said.
Responding to Patients
Like any other patient coming to a clinical visit, the most common reason patients are likely ordering these tests is that they’re seeking answers. Kim doesn’t typically see patients doing their own monitoring for diagnosed conditions between visits — the expense would add up too quickly — or testing for genetic markers, which likely wouldn’t be very helpful either.
“Even though most of our diseases probably have a genetic underpinning, how much it contributes is always unclear,” Dr. Kim said. Even conditions with clear genetic variants, such as familial Mediterranean fever, spondyloarthritis, and Behçet disease, can only support a diagnosis, not diagnose it on its own, Dr. Killeen said. And these are not among the tests currently available on most DTC company sites.
While there are also tests that can offer information about genetic risks for certain medications, such as a thiopurine methyltransferase test to find out if a patient lacks the enzyme needed to break down the immunosuppressant drug azathioprine, Kim hasn’t seen patients seeking these out either.
“The more global and more compassionate way to think about this is that we have a lot of people who are struggling to understand what’s going on with their bodies, and most physicians really don’t know what the next steps are for these people,” Dr. Kim said. “They’re desperate, and their quality of life is so poor that they’re going to take extreme steps to try to manage their own frustration with this condition.”
That means clinicians’ most powerful tools when patients come in with DTC test results are their listening skills.
“Empathy is the most important thing, just being able to share the patient’s frustration to the point where they had to take matters into their own hands,” Dr. Kim said. “I think a lot of rheumatologists are actually pretty comfortable being in this position.”
Additionally, doctors should know that some patients may be engaging in attempts to self-diagnose, self-treat, or otherwise self-manage their symptoms or perceived condition. “They just need to be aware and try to make sure there’s no harm being done,” Dr. Kim said.
Ms. Welsh didn’t seek treatment or diagnosis on her own, but getting her test also did not give her the control she was seeking. “Looking back, it was kind of a waste of money, but it felt good in the moment,” Ms. Welsh said. “I was so upset, and I wanted that control, and in the end, it didn’t get me results any sooner, and it didn’t give me peace of mind.”
It was Ms. Welsh’s primary care doctor listening to her concerns, ordering the same test she had ordered with several others, and working with her to seek answers that reassured her that her provider cared about her well-being.
“A lot of what I do in my business is reassure people that you know what they have is treatable or not going to end their life as they know it,” Dr. Putman said. “And you certainly can’t reassure them if they’re not in your clinic yet.”
Dr. Putman has participated in clinical trials with AbbVie, consulting with Novartis and GSK, and clinical trials and consulting with Amgen and AstraZeneca. Dr. Niewold reported receiving research grants from EMD Serono and Zenas BioPharma and consulting for Thermo Fisher Scientific, Progentec Diagnostics, Roivant Sciences, AstraZeneca, S3 Connected Health, Flagship Pioneering, and Guidepoint. Dr. Kim reported sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, Novartis, and CRISPR Therapeutics; royalties from Kypha; and consulting/speaking for Amgen, ANI Pharmaceuticals, Atara Biotherapeutics, Aurinia Pharmaceuticals, CARGO Therapeutics, Exagen Diagnostics, GSK, Hinge Bio, Kypha, Progentec Diagnostics, Synthekine, and UpToDate. Dr. Killeen had no relevant financial relationships to disclose.
A version of this article first appeared on Medscape.com.
When Jennifer Welsh, a 40-year-old from New Britain, Connecticut, visited her doctor about pain in her joints and neck, her doctor sent her to the emergency department (ED) to rule out meningitis. The ED did rule that out, as well as strep, so Ms. Welsh went to her follow-up appointment a few days later, hoping for answers or at least more tests to get those answers.
Instead, the doctor — a different one from the same practice as her primary care physician (PCP) — wouldn’t even talk to Ms. Welsh about her symptoms because she couldn’t see the ED’s results and refused to view the results that Ms. Welsh could pull up online.
“She just completely shut me down,” Ms. Welsh recalled. “It was a really awful appointment, and I left in tears. I was in physical pain, I had just been to the ER, nothing is really resolved, I’m stressed out about it, and this woman is completely dismissing me.”
She had been able to schedule an appointment with her regular PCP later that week, but after the harrowing experience with this doctor, she wondered if her PCP would order the rheumatoid arthritis (RA) test that Ms. Welsh suspected she needed. So, she took matters into her own hands.
“I was searching for what test to ask for from my doctor,” she said, and she found that she could order it on her own from a major lab company she was already familiar with. For around $100, “I could get it done and see what it says on my own,” she said.
But that’s not how it worked out. Her regular PCP apologized for the other doctor’s behavior and ordered the RA test as well as additional tests — and got results while Ms. Welsh still waited for the one she ordered to arrive over a week later.
At first, Ms. Welsh was grateful she could order the RA test without her doctor’s referral. “I felt it gave me a sense of control over the situation that I felt really not in control of, until the system failed me, and I didn’t get the results,” she said. But then, “not having someone I could call and get an answer about why my tests were delayed, why I wasn’t able to access them, why it was taking so long — it was definitely anxiety-inducing.”
A Growing Market
Ms. Welsh is one of a growing number of patients who are ordering direct-to-consumer (DTC) lab tests without the recommendation or guidance of a doctor. They’re offered online by labs ranging from well-established giants like Quest and Labcorp to smaller, potentially less vetted companies, although some smaller companies contract with larger companies like Quest. Combined, the DTC market is projected to be worth $2 billion by 2025.
Yet the burgeoning industry has also drawn critiques from both bioethicists and privacy experts. A research letter in JAMA in 2023, for example, found that less than half of the 21 companies identified in an online search declared Health Insurance Portability and Accountability Act compliance, while more than half “indicated the potential use of consumer data for research purposes either internally or through third-party sharing.” That study found the most commonly offered tests were related to diabetes, the thyroid, and vitamin levels, and hormone tests for men and women, such as testosterone or estradiol.
But a number of companies also offer tests related to rheumatologic conditions. A handful of tests offered by Labcorp, for example, could be used in rheumatology, such as tests for celiac antibodies or high-sensitivity C-reactive protein. Quest similarly offers a handful of autoimmune-related tests. But other companies offer a long slate of autoimmune or antibody tests.
The antinuclear antibody (ANA) test and RA panel offered by Quest are the same tests, run and analyzed in the same labs, as those ordered by physicians and hospitals, according to James Faix, MD, the medical director of immunology at Quest Diagnostics. Their RA panel includes rheumatoid factor and anti-cyclic citrullinated peptide as well as antibody to mutated citrullinated vimentin, “which may detect approximately 10%-15%” of patients who test negative to the first two.
Quest’s ANA test with reflex costs $112, and its RA panel costs $110, price points that are similar across other companies’ offerings. Labcorp declined to respond to questions about its DTC tests, and several smaller companies did not respond to queries about their offerings. It can therefore be hard to assess what’s included or what the quality is of many DTC tests, particularly from smaller, less established companies.
Oversight and Quality Control
Anthony Killeen, MD, PhD, president of the Association for Diagnostics & Laboratory Medicine (ADLM) and director of Clinical Laboratories at the University of Minnesota Medical Center in Minneapolis, said via email that the ADLM supports “expanding consumer access to direct-to-consumer laboratory testing services that have demonstrated analytical and clinical validity and clinical utility,” given the importance of individuals learning about their health status and becoming more involved in health decisions. But the ADLM also recommends “that only CLIA-certified laboratories perform direct-to-consumer testing,” he said.
“There are direct-to-consumer tests on the market that are not medical-grade laboratory tests and that may be performed in nonaccredited laboratories,” Dr. Killeen said. “We advise consumers to steer clear of such tests.” The ADLM also encourages consumers to “work with qualified healthcare providers when making decisions based off the results they receive from any direct-to-consumer tests” and recommends that DTC test companies “provide consumers with sufficient information and/or access to expert help to assist them in ordering tests and interpreting the results.”
Yet it’s unclear how much support, if any, consumers can receive in terms of understanding what their tests mean. Most of the companies in the 2023 study offered optional follow-up with a healthcare professional, but these professionals ranged from physicians to “health coaches,” and all the companies had disclaimers that “test results did not constitute medical advice.”
At Quest, the only company to respond to this news organization’s request for comment, consumer-initiated tests ordered online are first reviewed by a physician at PWNHealth, an independent, third-party physician network, to determine that it’s appropriate before the lab order is actually placed.
“Once results are available, individuals have the option to discuss their results with an independent physician at no extra cost,” Dr. Faix said. ANA or RA results outside the normal ranges may trigger a “call from a PWNHealth healthcare coordinator, who can help provide information, suggestions on next steps, and set up time for the individual to speak with an independent physician to discuss questions or concerns regarding the results,” he said.
“Our goal is not to replace the role of a healthcare provider,” Dr. Faix said. “We are providing an alternate way for people to engage with the healthcare system that offers convenience, gives people more control over their own healthcare journeys, and meets them where they are, supporting both consumers and their care teams.” The company has expanded its offerings from an initial 30 tests made available in 2018 to over 130 today, deciding which to offer “based on consumer research and expertise of clinical experts.” The company has also “seen steady interest in our two consumer rheumatology offerings,” Dr. Faix said.
The DTC Landscape in Rheumatology
Within rheumatology, among the most popular tests is for ANA, based on the experience of Alfred Kim, MD, PhD, associate professor of medicine at Washington University School of Medicine in St Louis, Missouri.
“For a lot of people, losing control over their health is maybe the most frightening experience they can have, so I think a lot of patients use this as a way to kind of have ownership over their health,” Dr. Kim said. “Let’s say they’ve been to four doctors. No one can explain what’s going on. They’re getting frustrated, and so they just turn to solutions where they feel like they have ownership over the situation.”
Though the market is undoubtedly growing, the growth appears uneven across geography and institution types. Kim has seen a “fair number of referrals,” with patients coming in with results from a DTC test. Michael Putman, MD, MSci, assistant professor of medicine at the Medical College of Wisconsin in Milwaukee, hasn’t seen it much. “I know that patients can get testing done themselves independently, but I don’t have people routinely coming in with tests they’ve ordered in advance of our appointment,” Dr. Putman said, but, like Dr. Kim, he recognizes why patients might seek them out.
“I’m a big fan of patient empowerment, and I do think that medicine serves a gatekeeper role that sometimes can be a little too far,” Dr. Putman said. “I think there is value to patients being able to get more information and try to understand what is happening in their bodies. I have a lot of compassion for someone who would try to find testing outside of the normal channels.”
Indeed, bringing these test results to a visit could be informative in some scenarios. A negative ANA test, for example, pretty much excludes lupus 100%, Dr. Kim said. But a positive ANA doesn’t tell him much, and if his clinical suspicion for a condition is high, he likely would order that test anyway, even if the patient came in with their own results. Dr. Putman also pointed out that the vast majority of tests used in rheumatology have a high rate of false positives.
“I think that will be the major area where this causes quite a lot of grief to patients and some frustration to some providers,” he said. A rheumatoid factor test like the one Ms. Welsh ordered, for example, might test positive in 10 out of 100 people randomly gathered in a room, but the majority of those individuals would not have RA, he said.
That test is another popular rheumatology one, according to Timothy Niewold, MD, vice chair for research in the Hospital for Special Surgery Department of Medicine in New York City. Among the possible reasons people might order these tests are the delay in diagnosis that can often occur with a lot of rheumatologic conditions and that “it can take a while to see a rheumatologist, depending on what part of the country you’re in and what the availability is,” he said. He’s not surprised to see tests for Sjögren disease among the offerings, for example, because it’s a condition that’s difficult to diagnose but reasonably common within autoimmune diseases.
Risks vs Benefits
DTC testing is not an answer to the national shortage of rheumatologists, however, especially given the risks that Dr. Niewold, Dr. Putman, and Dr. Kim worry outweigh potential benefits. On the one hand, getting online test results may help expedite a referral to a specialist, Dr. Niewold said. But a long wait for that appointment could then easily become a bigger source of anxiety than comfort, Dr. Putman said.
“It’s a trade-off where you are accepting a lot more people getting false-positive diagnoses and spending months thinking they have some disease where they might not, in exchange for a couple people who would have had a delayed diagnosis,” Dr. Putman said. “There’s an enormous amount of existential suffering,” that’s familiar to rheumatologists because some patients may dread the diagnosis of a rheumatic disease the way they might fear a cancer diagnosis, especially if they have lost a family member to a condition that they suspect they share, he said. “To put yourself into an existential catastrophe — that’s not a small harm.”
Dr. Niewold agreed, pointing out that patients with a positive ANA test may “get unnecessarily worried and stay up all night reading about lupus, getting scared for weeks on end before seeing a specialist.” And there are financial harms as well for patients who may order the same test multiple times, or a whole slate of tests, that they don’t need for hundreds or thousands of dollars. There’s also the lost time and effort of researching a condition or even seeking out support groups that patients may pursue, Dr. Niewold said.
The likely biggest risk to individuals, however, is the potential for overdiagnosis or misdiagnosis.
“If someone comes in and they’ve read the textbook on lupus and they have a positive ANA, it’s really hard as a rheumatologist to walk that back,” Dr. Putman said. “The human mind is a powerful thing,” he added, and people who get a positive test will likely start to notice things like joint pain or a rash on their cheeks and begin attributing it to a diagnosis they risk convincing themselves they have. “When people come into your clinic not knowing what a disease would look like and they just tell you how they’re feeling, it’s a much cleaner and more honest way to approach diagnosis.”
Most patients likely don’t realize, for example, that none of the tests rheumatologists usually order are diagnostic in and of themselves, Dr. Niewold said. “They’re all kind of like stars in the constellation of a diagnosis,” he said. “They’re helpful, but none of them is sufficient by itself.”
Dr. Killeen agreed, noting that “consumers might not understand the nuances of these tests well enough to know whether it is appropriate to order them or how to interpret the results correctly.” Given the long-term implications of a diagnosis for a rheumatologic disease, “I would have concerns about consumers ordering and interpreting rheumatologic tests without working closely with their physicians,” Dr. Killeen said. “The main concern that lab experts have about direct-to-consumer tests is the potential for people to get misleading results and/or to misinterpret their results, which in turn could lead to people not getting the treatment they need or getting treatment when they don’t need any at all.”
It’s one thing for patients to come in asking for a particular treatment they may not need but which a doctor may be able to dissuade them from seeking. But Dr. Kim also pointed out the risk that patients may decide to treat themselves with therapies that haven’t undergone rigorous testing or haven’t been recommended by a physician.
“We tend to have people who come in with a pretty clear idea of what they want done, but the problem is, we don’t know if their reasoning is correct from a clinical perspective,” Dr. Kim said. Companies offer these tests with the belief that they’re “providing patients a choice, an option to take ownership,” he said, “but the potential harm can be realized very quickly because there are going to be people who are misdiagnosing themselves and, worse yet, may then pursue their own treatment plan that’s going in the opposite direction of where we think it needs to go.”
Or, on the flip side, if a patient erroneously believes they have the answer to what ails them, it may delay diagnosis of a more serious condition that’s rarer or harder to detect. Kim pointed to, for example, intravascular lymphoma, which is notoriously as difficult to identify as it is rare and aggressive. If a patient’s confirmation bias has led them to believe they have an autoimmune condition, they may not receive the more serious diagnosis until it’s advanced too far to treat.
Patient-Provider Relationship Friction
Another concern is how these tests may lead to confusion and frustration that can erode the patient-provider relationship, particularly because most patients don’t know how to interpret the results or understand the bigger context in which the results have to be interpreted. Many patients may think a test can come back with a binary answer, a positive or negative, and that means they do or don’t have a condition. That’s generally true for pregnancy tests, COVID tests, and sexually transmitted infection tests — the kinds of tests that have long been available to consumers and which have fairly straightforward answers.
But physicians know that’s not the case for many conditions, particularly those in rheumatology.
“In rheumatic diseases, because the tests have such marginal value in terms of diagnosis, almost always we develop a suspicion before we even think about ordering the tests, and then that dictates whether or not we cross that threshold,” Dr. Kim said. “A negative test doesn’t exclude the fact that you may have disease X, but a positive test also doesn’t mean you have disease X. All they provide is an idea of the risk.”
But some patients who come in with DTC test results have “already made the decision in their mind that they have a certain condition,” Dr. Kim said. “This is obviously dangerous because the majority of these patients do not have the condition they think they have, and it leaves a very uncomfortable feeling after the visit because they feel like they’ve been either betrayed by me or by the test, and they leave more confused.”
Patients may also come in with tests that a doctor isn’t familiar with or isn’t sure how to interpret on its own, at least for that particular patient.
“For ANA testing, we have a pretty good idea of its positive and negative predictive value because it’s ordered so much, but for many of these tests being offered, there are specific autoantibodies, and we tend to only get them in people where there’s a clinical suspicion,” Dr. Kim said. “Within that very specific context, we kind of understand what that value means, but if you give it to the general public, then those numbers aren’t as applicable and most likely overestimate the risk of disease.”
Even if providers consider the results of a DTC test in their differential, they may want to be sure it’s from a trustworthy source. “If a provider is uncertain about whether a direct-to-consumer testing company is reputable or about whether a direct-to-consumer test result is reliable, I would encourage them to consult with their laboratory medicine colleagues,” Dr. Killeen said.
Responding to Patients
Like any other patient coming to a clinical visit, the most common reason patients are likely ordering these tests is that they’re seeking answers. Kim doesn’t typically see patients doing their own monitoring for diagnosed conditions between visits — the expense would add up too quickly — or testing for genetic markers, which likely wouldn’t be very helpful either.
“Even though most of our diseases probably have a genetic underpinning, how much it contributes is always unclear,” Dr. Kim said. Even conditions with clear genetic variants, such as familial Mediterranean fever, spondyloarthritis, and Behçet disease, can only support a diagnosis, not diagnose it on its own, Dr. Killeen said. And these are not among the tests currently available on most DTC company sites.
While there are also tests that can offer information about genetic risks for certain medications, such as a thiopurine methyltransferase test to find out if a patient lacks the enzyme needed to break down the immunosuppressant drug azathioprine, Kim hasn’t seen patients seeking these out either.
“The more global and more compassionate way to think about this is that we have a lot of people who are struggling to understand what’s going on with their bodies, and most physicians really don’t know what the next steps are for these people,” Dr. Kim said. “They’re desperate, and their quality of life is so poor that they’re going to take extreme steps to try to manage their own frustration with this condition.”
That means clinicians’ most powerful tools when patients come in with DTC test results are their listening skills.
“Empathy is the most important thing, just being able to share the patient’s frustration to the point where they had to take matters into their own hands,” Dr. Kim said. “I think a lot of rheumatologists are actually pretty comfortable being in this position.”
Additionally, doctors should know that some patients may be engaging in attempts to self-diagnose, self-treat, or otherwise self-manage their symptoms or perceived condition. “They just need to be aware and try to make sure there’s no harm being done,” Dr. Kim said.
Ms. Welsh didn’t seek treatment or diagnosis on her own, but getting her test also did not give her the control she was seeking. “Looking back, it was kind of a waste of money, but it felt good in the moment,” Ms. Welsh said. “I was so upset, and I wanted that control, and in the end, it didn’t get me results any sooner, and it didn’t give me peace of mind.”
It was Ms. Welsh’s primary care doctor listening to her concerns, ordering the same test she had ordered with several others, and working with her to seek answers that reassured her that her provider cared about her well-being.
“A lot of what I do in my business is reassure people that you know what they have is treatable or not going to end their life as they know it,” Dr. Putman said. “And you certainly can’t reassure them if they’re not in your clinic yet.”
Dr. Putman has participated in clinical trials with AbbVie, consulting with Novartis and GSK, and clinical trials and consulting with Amgen and AstraZeneca. Dr. Niewold reported receiving research grants from EMD Serono and Zenas BioPharma and consulting for Thermo Fisher Scientific, Progentec Diagnostics, Roivant Sciences, AstraZeneca, S3 Connected Health, Flagship Pioneering, and Guidepoint. Dr. Kim reported sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, Novartis, and CRISPR Therapeutics; royalties from Kypha; and consulting/speaking for Amgen, ANI Pharmaceuticals, Atara Biotherapeutics, Aurinia Pharmaceuticals, CARGO Therapeutics, Exagen Diagnostics, GSK, Hinge Bio, Kypha, Progentec Diagnostics, Synthekine, and UpToDate. Dr. Killeen had no relevant financial relationships to disclose.
A version of this article first appeared on Medscape.com.
Commentary: PsA Targeted Therapy Trials, October 2024
Matching adjusted indirect comparison is one method of evaluating comparative effectiveness. To compare the efficacy between bimekizumab, an interleukin (IL) 17A/F inhibitor and risankizumab, an IL-23 inhibitor, Mease et al conducted such a study using data from four phase 3 trials (BE OPTIMAL, BE COMPLETE, KEEPsAKE-1, and KEEPsAKE-2) involving patients who were biologic-naive or inadequate responders to tumour necrosis factor (TNF) inhibitors who received bimekizumab (n = 698) or risankizumab (n = 589).1
At week 52, bimekizumab led to a higher likelihood of achieving a ≥ 70% improvement in the American College of Rheumatology (ACR) response in patients who were biologic-naive and TNF inhibitor inadequate responders (TNFi-IR), compared with risankizumab. Bimekizumab also had greater odds of achieving minimal disease activity in patients who were TNFi-IR. Thus, bimekizumab may be superior to risankizumab for treating those with PsA. Randomized controlled head-to-head clinical trials are required to confirm these findings.
In regard to long-term safety and efficacy of bimekizumab, Mease et al reported that bimekizumab demonstrated consistent safety and sustained efficacy for up to 2 years in patients with PsA.2 In this open-label extension (BE VITAL) of two phase 3 trials that included biologic-naive (n = 852) and TNFi-IR (n = 400) patients with PsA who were randomly assigned to receive bimekizumab, placebo with crossover to bimekizumab at week 16, or adalimumab followed by bimekizumab at week 52, no new safety signals were noted from weeks 52 to 104,. SARS-CoV-2 infection was the most common treatment-emergent adverse event. Approximately 50% of biologic-naive and TNFi-IR patients maintained a 50% or greater improvement in the ACR response.
Guselkumab, another IL-23 inhibitor, has proven efficacy in treating PsA. Curtis et al investigated the impact of early achievement of improvement with guselkumab and longer-term outcomes.3 This was a post hoc analysis of two phase 3 trials, DISCOVER-1 and DISCOVER-2, which included 1120 patients with active PsA who received guselkumab every 4 or 8 weeks (Q4W) or placebo with a crossover to guselkumab Q4W at week 24. The study demonstrated that guselkumab led to early achievement of minimal clinically important improvement (MCII) in clinical disease activity index for PsA (cDAPSA), with higher response rates at week 4 compared with placebo. Moreover, achieving early MCII in cDAPSA was associated with sustained disease control at weeks 24 and 52. Thus, guselkumab treatment achieved MCII in cDAPSA after the first dose and sustained disease control for up to 1 year. Early treatment response and a proven safety record make guselkumab an attractive treatment option for PsA.
PsA clinical trials mostly include patients with polyarthritis. Little is known about treatment efficacy for oligoarticular PsA. To address this gap in knowledge, Gossec et al reported the results of the phase 4 FOREMOST trial that included 308 patients with early (symptom duration 5 years or less) targeted therapy–naive oligoarticular PsA and were randomly assigned to receive apremilast (n = 203) or placebo (n = 105).4 At week 16, a higher proportion of patients receiving apremilast achieved minimal disease activity (joints response) compared with those receiving placebo. No new safety signals were reported. Apremilast is thus efficacious in treating early oligoarticular PsA as well as polyarticular PsA and psoriasis. Similar studies with other targeted therapies will help clinicians better manage early oligoarticular PsA.
References
- Mease PJ, Warren RB, Nash P, et al. Comparative effectiveness of bimekizumab and risankizumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 Aug 9. Source
- Mease PJ, Merola JF, Tanaka Y, et al. Safety and efficacy of bimekizumab in patients with psoriatic arthritis: 2-year results from two phase 3 studies. Rheumatol Ther. 2024 Aug 31. Source
- Curtis JR, et al. Early improvements with guselkumab associate with sustained control of psoriatic arthritis: post hoc analyses of two phase 3 trials. Rheumatol Ther. 2024 Sep 11. Source
- Gossec L, Coates LC, Gladman DD, et al. Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial. Ann Rheum Dis. 2024 Sep 16:ard-2024-225833. Source
Matching adjusted indirect comparison is one method of evaluating comparative effectiveness. To compare the efficacy between bimekizumab, an interleukin (IL) 17A/F inhibitor and risankizumab, an IL-23 inhibitor, Mease et al conducted such a study using data from four phase 3 trials (BE OPTIMAL, BE COMPLETE, KEEPsAKE-1, and KEEPsAKE-2) involving patients who were biologic-naive or inadequate responders to tumour necrosis factor (TNF) inhibitors who received bimekizumab (n = 698) or risankizumab (n = 589).1
At week 52, bimekizumab led to a higher likelihood of achieving a ≥ 70% improvement in the American College of Rheumatology (ACR) response in patients who were biologic-naive and TNF inhibitor inadequate responders (TNFi-IR), compared with risankizumab. Bimekizumab also had greater odds of achieving minimal disease activity in patients who were TNFi-IR. Thus, bimekizumab may be superior to risankizumab for treating those with PsA. Randomized controlled head-to-head clinical trials are required to confirm these findings.
In regard to long-term safety and efficacy of bimekizumab, Mease et al reported that bimekizumab demonstrated consistent safety and sustained efficacy for up to 2 years in patients with PsA.2 In this open-label extension (BE VITAL) of two phase 3 trials that included biologic-naive (n = 852) and TNFi-IR (n = 400) patients with PsA who were randomly assigned to receive bimekizumab, placebo with crossover to bimekizumab at week 16, or adalimumab followed by bimekizumab at week 52, no new safety signals were noted from weeks 52 to 104,. SARS-CoV-2 infection was the most common treatment-emergent adverse event. Approximately 50% of biologic-naive and TNFi-IR patients maintained a 50% or greater improvement in the ACR response.
Guselkumab, another IL-23 inhibitor, has proven efficacy in treating PsA. Curtis et al investigated the impact of early achievement of improvement with guselkumab and longer-term outcomes.3 This was a post hoc analysis of two phase 3 trials, DISCOVER-1 and DISCOVER-2, which included 1120 patients with active PsA who received guselkumab every 4 or 8 weeks (Q4W) or placebo with a crossover to guselkumab Q4W at week 24. The study demonstrated that guselkumab led to early achievement of minimal clinically important improvement (MCII) in clinical disease activity index for PsA (cDAPSA), with higher response rates at week 4 compared with placebo. Moreover, achieving early MCII in cDAPSA was associated with sustained disease control at weeks 24 and 52. Thus, guselkumab treatment achieved MCII in cDAPSA after the first dose and sustained disease control for up to 1 year. Early treatment response and a proven safety record make guselkumab an attractive treatment option for PsA.
PsA clinical trials mostly include patients with polyarthritis. Little is known about treatment efficacy for oligoarticular PsA. To address this gap in knowledge, Gossec et al reported the results of the phase 4 FOREMOST trial that included 308 patients with early (symptom duration 5 years or less) targeted therapy–naive oligoarticular PsA and were randomly assigned to receive apremilast (n = 203) or placebo (n = 105).4 At week 16, a higher proportion of patients receiving apremilast achieved minimal disease activity (joints response) compared with those receiving placebo. No new safety signals were reported. Apremilast is thus efficacious in treating early oligoarticular PsA as well as polyarticular PsA and psoriasis. Similar studies with other targeted therapies will help clinicians better manage early oligoarticular PsA.
References
- Mease PJ, Warren RB, Nash P, et al. Comparative effectiveness of bimekizumab and risankizumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 Aug 9. Source
- Mease PJ, Merola JF, Tanaka Y, et al. Safety and efficacy of bimekizumab in patients with psoriatic arthritis: 2-year results from two phase 3 studies. Rheumatol Ther. 2024 Aug 31. Source
- Curtis JR, et al. Early improvements with guselkumab associate with sustained control of psoriatic arthritis: post hoc analyses of two phase 3 trials. Rheumatol Ther. 2024 Sep 11. Source
- Gossec L, Coates LC, Gladman DD, et al. Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial. Ann Rheum Dis. 2024 Sep 16:ard-2024-225833. Source
Matching adjusted indirect comparison is one method of evaluating comparative effectiveness. To compare the efficacy between bimekizumab, an interleukin (IL) 17A/F inhibitor and risankizumab, an IL-23 inhibitor, Mease et al conducted such a study using data from four phase 3 trials (BE OPTIMAL, BE COMPLETE, KEEPsAKE-1, and KEEPsAKE-2) involving patients who were biologic-naive or inadequate responders to tumour necrosis factor (TNF) inhibitors who received bimekizumab (n = 698) or risankizumab (n = 589).1
At week 52, bimekizumab led to a higher likelihood of achieving a ≥ 70% improvement in the American College of Rheumatology (ACR) response in patients who were biologic-naive and TNF inhibitor inadequate responders (TNFi-IR), compared with risankizumab. Bimekizumab also had greater odds of achieving minimal disease activity in patients who were TNFi-IR. Thus, bimekizumab may be superior to risankizumab for treating those with PsA. Randomized controlled head-to-head clinical trials are required to confirm these findings.
In regard to long-term safety and efficacy of bimekizumab, Mease et al reported that bimekizumab demonstrated consistent safety and sustained efficacy for up to 2 years in patients with PsA.2 In this open-label extension (BE VITAL) of two phase 3 trials that included biologic-naive (n = 852) and TNFi-IR (n = 400) patients with PsA who were randomly assigned to receive bimekizumab, placebo with crossover to bimekizumab at week 16, or adalimumab followed by bimekizumab at week 52, no new safety signals were noted from weeks 52 to 104,. SARS-CoV-2 infection was the most common treatment-emergent adverse event. Approximately 50% of biologic-naive and TNFi-IR patients maintained a 50% or greater improvement in the ACR response.
Guselkumab, another IL-23 inhibitor, has proven efficacy in treating PsA. Curtis et al investigated the impact of early achievement of improvement with guselkumab and longer-term outcomes.3 This was a post hoc analysis of two phase 3 trials, DISCOVER-1 and DISCOVER-2, which included 1120 patients with active PsA who received guselkumab every 4 or 8 weeks (Q4W) or placebo with a crossover to guselkumab Q4W at week 24. The study demonstrated that guselkumab led to early achievement of minimal clinically important improvement (MCII) in clinical disease activity index for PsA (cDAPSA), with higher response rates at week 4 compared with placebo. Moreover, achieving early MCII in cDAPSA was associated with sustained disease control at weeks 24 and 52. Thus, guselkumab treatment achieved MCII in cDAPSA after the first dose and sustained disease control for up to 1 year. Early treatment response and a proven safety record make guselkumab an attractive treatment option for PsA.
PsA clinical trials mostly include patients with polyarthritis. Little is known about treatment efficacy for oligoarticular PsA. To address this gap in knowledge, Gossec et al reported the results of the phase 4 FOREMOST trial that included 308 patients with early (symptom duration 5 years or less) targeted therapy–naive oligoarticular PsA and were randomly assigned to receive apremilast (n = 203) or placebo (n = 105).4 At week 16, a higher proportion of patients receiving apremilast achieved minimal disease activity (joints response) compared with those receiving placebo. No new safety signals were reported. Apremilast is thus efficacious in treating early oligoarticular PsA as well as polyarticular PsA and psoriasis. Similar studies with other targeted therapies will help clinicians better manage early oligoarticular PsA.
References
- Mease PJ, Warren RB, Nash P, et al. Comparative effectiveness of bimekizumab and risankizumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 Aug 9. Source
- Mease PJ, Merola JF, Tanaka Y, et al. Safety and efficacy of bimekizumab in patients with psoriatic arthritis: 2-year results from two phase 3 studies. Rheumatol Ther. 2024 Aug 31. Source
- Curtis JR, et al. Early improvements with guselkumab associate with sustained control of psoriatic arthritis: post hoc analyses of two phase 3 trials. Rheumatol Ther. 2024 Sep 11. Source
- Gossec L, Coates LC, Gladman DD, et al. Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial. Ann Rheum Dis. 2024 Sep 16:ard-2024-225833. Source
How the Future of Medicine Will Revolve Around Our Gut
Meet your new patients.
You can’t see them, but trillions — maybe quadrillions — of them travel in and out of your practice every day. They’re hungry, mysterious, community-oriented, and small. Very, very small.
They’re the microbes occupying your current patients’ guts.
Someday soon, you’ll prescribe medicine not just for humans but also for these microbes.
“I am convinced in the future our medicine cabinets are going to have not just medications like a statin for treating us, but [also] pills that treat and inhibit an enzyme in our microbes and elicit a health benefit in some chronic disease,” said Stanley Hazen, MD, PhD, co-section head of Preventive Cardiology & Rehabilitation and director of the Center for Microbiome & Human Health at Cleveland Clinic, Cleveland, Ohio.
These trillions of microbes use our food to generate substances called metabolites that can protect or harm our health, with consequences reaching far beyond our gastrointestinal tracts.
Research has linked microbial metabolites to diabetes, cardiovascular disease, liver disease, obesity, high blood pressure, neurological disorders, depression, cancer, and more. Gastroenterologist Christopher Damman, MD, a clinical associate professor at the University of Washington Medical Center, Seattle, calls it a “growing theme” in microbiome science.
Now scientists are developing treatments targeting gut microbial pathways, designed to eliminate the bad metabolites and boost the good metabolites.
One close to human therapeutic intervention is an oral treatment from Dr. Hazen’s lab targeting the metabolite trimethylamine N-oxide (TMAO), a predictor of and contributor to both cardiovascular disease and chronic kidney disease. The drug, which blocks TMAO formation, is nearing clinical trials, Dr. Hazen said.
The advantage is safety. By targeting the microbe instead of, say, an enzyme, the host (your patient) must absorb little if any drug.
Implications for the future of medicine are huge. “Gut microbial pathways contribute to diabetes, obesity, virtually everything,” Dr. Hazen said. “Therapies that target gut microbiome processes will probably even be used for psychiatric disorders within, I’ll say, 10 or 20 years.”
The Science
About 100 trillion strains of bacteria live in our guts. As humans have evolved, so have they.
Between 70% and 90% come from the phyla Firmicutes and Bacteroidetes, with person-to-person variation shaped by genetics, environment, and lifestyle.
“Everyone’s microbiome is subtly different,” said Dr. Hazen. “So the combination of what they’re making is different. All these different biologically active compounds are influencing us in subtly different ways.”
How it works: When you eat, your microbes eat, breaking down food into metabolites that interact with the thin layer of epithelial cells lining your gut. Some can be absorbed through the lining and into your bloodstream, a phenomenon known as “leaky gut.” Once in your blood, they can trigger irritation and inflammation, potentially leading to a wide variety of health issues, from gas and bloating to autoimmune conditions and mood disorders.
“On the other side of the epithelial lining, you have some of the largest concentrations of immune cells,” said Narendra Kumar, PhD, associate professor of pharmaceutical sciences at Texas A&M University, College Station, Texas.
Metabolites can influence how these immune cells work, possibly explaining why each person’s immune system behaves distinctively.
Of the 1000-plus metabolites linked to the gut microbiome, scientists have identified several that matter.
Short-chain fatty acids. When we eat fiber, colon bacteria ferment it into the beneficial short-chain fatty acids acetate, propionate, and butyrate. These bind to receptors in muscle, liver, and fat tissue, affecting the secretion of gut hormones and peptides related to appetite, inflammation, energy expenditure, and fat oxidation.
Butyrate has been linked to health benefits. It supports the integrity of the gut’s lining, stifling pathogenic gut bacteria, fighting cancer-promoting inflammation, and protecting against obesity and diabetes. It can function as a prebiotic, helping beneficial bacteria thrive. And recent studies linked an abundance of butyrate-producing bacteria with reduced bone fracture risk and hospitalization for infectious disease.
TMAO and phenylacetylglutamine. When we eat foods rich in animal proteins — think eggs, milk, fish, and especially red meat — some gut bacteria convert nutrients like choline and L-carnitine into TMAO and phenylalanine into phenylacetylglutamine. Research conducted by Dr. Hazen’s lab and replicated by others has linked both metabolites to heart problems.
In a landmark study from Dr. Hazen’s group, healthy adults who went on to develop coronary artery disease had significantly higher plasma TMAO levels than those who did not wind up with the condition. The association remained strong, even after controlling for risk factors like age, sex, smoking, high blood pressure, and high cholesterol.
In preclinical studies, elevated TMAO enhanced cardiovascular disease. TMAO-producing microbes also accentuated cardiovascular disease phenotypes in mouse models, while blocking these pathways inhibited the phenotypes.
Research suggests TMAO may harm cardiomyocytes (cells that contract and relax the heart) in dozens of ways, such as activating the expression of proteins to promote hypertrophy and fibrosis, decreasing mitochondrial function, and disrupting calcium signaling.
Another study linked phenylacetylglutamine levels to cardiac event risk in patients with heart failure. Recent mechanistic investigations suggest the metabolite alters signaling in a beta-adrenergic receptor involved in our fight-or-flight response, said Hazen.
“It’s like a rheostat on the light switch, a dimmer switch, and it’s what’s called a negative allosteric modulator,” he said. “It’s the first time that this type of behavior has ever been shown to be present for a gut microbial metabolite and a host receptor.”
Tryptophan metabolites. Microbes in your colon can convert the amino acid tryptophan, also found in animal-based foods, into neurotransmitters like serotonin and melatonin.
“The enteric nervous system, the nervous system around the gut, is immense,” said James Versalovic, MD, PhD, professor of pathology and immunology at Baylor College of Medicine, Houston. “The gut-brain axis has become a very fertile area of research.”
Lesser-known tryptophan metabolites — like indole, tryptamine, and indoleethanol — have been linked to benefits like fortifying the gut barrier, promoting the release of glucagon-like peptide 1 to reduce appetite, and protecting the liver from hepatitis. However, indole can also spur the production of indoxyl sulfate, a toxin linked to chronic kidney disease.
Bile acid byproducts. Your gut bugs also feast on (and transform) bile acids before they reabsorb and travel back to the liver.
Research is gaining traction on these secondary bile acids, which can affect inflammation and immune function in helpful and harmful ways.
One area of interest is how microbes break down hormones in bile. A recent study from Harvard showed that gut microbes convert corticoid hormones in bile into progestins, which could affect postpartum depression risk. And researchers are exploring the estrobolome — a gut microbial community dedicated to breaking down estrogen into its active form so it can be reabsorbed.
“Depending on the bacteria that you have, more or less can be recirculated back into your blood,” said Beatriz Peñalver Bernabé, PhD, an assistant professor of biomedical engineering and urology at the University of Illinois Chicago. “So you may be producing the same amount of estrogen, but depending on the bacteria you have, the real free estrogen that can bind to your cells may be very different.”
The gut microbiome can also regulate testosterone, with studies showing microbial differences in men with high testosterone vs those with less.
What Patients Can Do Now
Advances in the field of microbiome research — and the related “gut health” wellness craze — have spawned all kinds of new microbiome-based products: Like over-the-counter probiotic supplements and at-home test kits, which let you send a stool sample for analysis to reveal microbiome health and personalized diet recommendations.
But the science behind these tests is still evolving, said Dr. Damman. “The clinical inferences and applications are still pretty limited.”
For most people, the first step to fostering healthier microbial metabolites is much simpler: Diversify your diet.
“A lot of folks are missing that diversity,” Dr. Damman said.
“Eat foods and experiment with foods that you might not eat all the time,” especially fruits, vegetables, nuts, seeds, and beans.
Another strategy: Eat foods with probiotic bacteria. “I view it as an insurance policy,” said Dr. Versalovic, “fortifying my gut with probiotics, with daily yogurt, for example, at breakfast.”
Fermented foods like kimchi and kombucha can also increase microbial diversity and can even contain health-promoting postbiotics, research shows.
As for probiotic supplements, the jury’s still out.
Certain strains of probiotic bacteria may be beneficial for some patients, like those with diarrhea, Crohn’s disease, and irritable bowel syndrome, according to World Gastroenterology Organisation guidelines.
As with other interventions, individual responses can vary. A Stanford study showed that some people with metabolic syndrome improved when taking a probiotic, while others didn’t. Both groups had key differences in gut bacteria and dietary habits.
For best results, such microbiome-based interventions will need to be personalized, experts say. And the technology to do that is coming sooner than you might think.
Microbiome’s Medical Future: ‘We Are on the Cusp of a New Era’
In just a few years, artificial intelligence (AI) models could predict gut microbial composition based on data such as dietary habits and household characteristics, Dr. Kumar said.
Advancements in metabolomics and bioinformatics could soon help physicians and patients personalize their treatment approaches, said Dr. Damman.
One focus will be on fortifying the gut with whatever it lacks.
“In those individuals where certain microbes are missing, (a) how could we add them back potentially in a rational, science-driven way, and (b) maybe some of those factors that the microbes are producing out the other ends, you could give directly,” said Dr. Damman.
For example, multiple companies make butyrate as a dietary supplement, although the research is too early to support widespread use. Another option could be eating something that spurs butyrate production. One small study found that a fiber supplement formulated to increase butyrate levels in the colon reduced participants’ systolic blood pressure by an average of six points.
Another option could be synbiotics, products that combine bacteria and the food source they feed on. “If you just give a diet-based therapy, it is not going to work as much. Because what if that diet needs certain bacteria to have these beneficial metabolites?” said Ashutosh Mangalam, PhD, associate professor of pathology at the University of Iowa Carver College of Medicine, Iowa City.
Dr. Mangalam studies links between bacterial metabolism of phytoestrogens in soy foods and multiple sclerosis (MS) development. He is using AI to understand differences in metabolites in patients with MS vs healthy controls to determine how to target them.
Gut microbial metabolites could also affect disease screening and intervention. What if gut microbe sequencing could predict a pregnant person’s risk of developing depression, something now assessed through simple questionnaires?
“Imagine that your doctor says, ‘Okay, give me a poop sample,’ ” Dr. Bernabé said. “Then they phenotype it, and then they put it in your electronic medical record, and they say, ‘Well, you have high likelihood of having a mood disorder down the line in your pregnancy. Why don’t we directly refer you to a provider now so you can follow up?’ ”
Research is already underway to understand how metabolites might be linked to pregnancy outcomes, complex regional pain syndrome, and anxiety. Researchers are also investigating whether supplementing our diets with things like prebiotic fibers, apple polyphenols, or tomato paste might influence metabolites. And fecal transplants that shift the gut microbiome and metabolites could have potential in diseases like unexplained atherosclerosis, post-COVID syndrome, and hidradenitis suppurativa.
Dr. Hazen’s discovery linking TMAO with cardiovascular risk has already changed clinical practice. A blood TMAO test can help identify patients at risk who may not have traditional risk factors. “Millions have been done,” Dr. Hazen said.
Meanwhile, his drug targeting the TMAO pathway inches closer to clinical trials.
“In an animal model, we elicit improvement in heart failure, renal disease, atherosclerosis, thrombosis, aortic aneurysm, and obesity,” Dr. Hazen said. The first clinical trials will focus on renal disease.
As with any drug, the road to approval takes time. And success is not guaranteed.
But Dr. Hazen for one is optimistic.
“We are on the cusp of a new era,” Dr. Hazen said. “Like when humans first discovered insulin and glucagon were hormones that impact sugar metabolism. We now recognize myriad new ‘hormones’ in the form of gut microbiome metabolites that impact our physiology and susceptibility to diseases.”
A version of this article first appeared on Medscape.com.
Meet your new patients.
You can’t see them, but trillions — maybe quadrillions — of them travel in and out of your practice every day. They’re hungry, mysterious, community-oriented, and small. Very, very small.
They’re the microbes occupying your current patients’ guts.
Someday soon, you’ll prescribe medicine not just for humans but also for these microbes.
“I am convinced in the future our medicine cabinets are going to have not just medications like a statin for treating us, but [also] pills that treat and inhibit an enzyme in our microbes and elicit a health benefit in some chronic disease,” said Stanley Hazen, MD, PhD, co-section head of Preventive Cardiology & Rehabilitation and director of the Center for Microbiome & Human Health at Cleveland Clinic, Cleveland, Ohio.
These trillions of microbes use our food to generate substances called metabolites that can protect or harm our health, with consequences reaching far beyond our gastrointestinal tracts.
Research has linked microbial metabolites to diabetes, cardiovascular disease, liver disease, obesity, high blood pressure, neurological disorders, depression, cancer, and more. Gastroenterologist Christopher Damman, MD, a clinical associate professor at the University of Washington Medical Center, Seattle, calls it a “growing theme” in microbiome science.
Now scientists are developing treatments targeting gut microbial pathways, designed to eliminate the bad metabolites and boost the good metabolites.
One close to human therapeutic intervention is an oral treatment from Dr. Hazen’s lab targeting the metabolite trimethylamine N-oxide (TMAO), a predictor of and contributor to both cardiovascular disease and chronic kidney disease. The drug, which blocks TMAO formation, is nearing clinical trials, Dr. Hazen said.
The advantage is safety. By targeting the microbe instead of, say, an enzyme, the host (your patient) must absorb little if any drug.
Implications for the future of medicine are huge. “Gut microbial pathways contribute to diabetes, obesity, virtually everything,” Dr. Hazen said. “Therapies that target gut microbiome processes will probably even be used for psychiatric disorders within, I’ll say, 10 or 20 years.”
The Science
About 100 trillion strains of bacteria live in our guts. As humans have evolved, so have they.
Between 70% and 90% come from the phyla Firmicutes and Bacteroidetes, with person-to-person variation shaped by genetics, environment, and lifestyle.
“Everyone’s microbiome is subtly different,” said Dr. Hazen. “So the combination of what they’re making is different. All these different biologically active compounds are influencing us in subtly different ways.”
How it works: When you eat, your microbes eat, breaking down food into metabolites that interact with the thin layer of epithelial cells lining your gut. Some can be absorbed through the lining and into your bloodstream, a phenomenon known as “leaky gut.” Once in your blood, they can trigger irritation and inflammation, potentially leading to a wide variety of health issues, from gas and bloating to autoimmune conditions and mood disorders.
“On the other side of the epithelial lining, you have some of the largest concentrations of immune cells,” said Narendra Kumar, PhD, associate professor of pharmaceutical sciences at Texas A&M University, College Station, Texas.
Metabolites can influence how these immune cells work, possibly explaining why each person’s immune system behaves distinctively.
Of the 1000-plus metabolites linked to the gut microbiome, scientists have identified several that matter.
Short-chain fatty acids. When we eat fiber, colon bacteria ferment it into the beneficial short-chain fatty acids acetate, propionate, and butyrate. These bind to receptors in muscle, liver, and fat tissue, affecting the secretion of gut hormones and peptides related to appetite, inflammation, energy expenditure, and fat oxidation.
Butyrate has been linked to health benefits. It supports the integrity of the gut’s lining, stifling pathogenic gut bacteria, fighting cancer-promoting inflammation, and protecting against obesity and diabetes. It can function as a prebiotic, helping beneficial bacteria thrive. And recent studies linked an abundance of butyrate-producing bacteria with reduced bone fracture risk and hospitalization for infectious disease.
TMAO and phenylacetylglutamine. When we eat foods rich in animal proteins — think eggs, milk, fish, and especially red meat — some gut bacteria convert nutrients like choline and L-carnitine into TMAO and phenylalanine into phenylacetylglutamine. Research conducted by Dr. Hazen’s lab and replicated by others has linked both metabolites to heart problems.
In a landmark study from Dr. Hazen’s group, healthy adults who went on to develop coronary artery disease had significantly higher plasma TMAO levels than those who did not wind up with the condition. The association remained strong, even after controlling for risk factors like age, sex, smoking, high blood pressure, and high cholesterol.
In preclinical studies, elevated TMAO enhanced cardiovascular disease. TMAO-producing microbes also accentuated cardiovascular disease phenotypes in mouse models, while blocking these pathways inhibited the phenotypes.
Research suggests TMAO may harm cardiomyocytes (cells that contract and relax the heart) in dozens of ways, such as activating the expression of proteins to promote hypertrophy and fibrosis, decreasing mitochondrial function, and disrupting calcium signaling.
Another study linked phenylacetylglutamine levels to cardiac event risk in patients with heart failure. Recent mechanistic investigations suggest the metabolite alters signaling in a beta-adrenergic receptor involved in our fight-or-flight response, said Hazen.
“It’s like a rheostat on the light switch, a dimmer switch, and it’s what’s called a negative allosteric modulator,” he said. “It’s the first time that this type of behavior has ever been shown to be present for a gut microbial metabolite and a host receptor.”
Tryptophan metabolites. Microbes in your colon can convert the amino acid tryptophan, also found in animal-based foods, into neurotransmitters like serotonin and melatonin.
“The enteric nervous system, the nervous system around the gut, is immense,” said James Versalovic, MD, PhD, professor of pathology and immunology at Baylor College of Medicine, Houston. “The gut-brain axis has become a very fertile area of research.”
Lesser-known tryptophan metabolites — like indole, tryptamine, and indoleethanol — have been linked to benefits like fortifying the gut barrier, promoting the release of glucagon-like peptide 1 to reduce appetite, and protecting the liver from hepatitis. However, indole can also spur the production of indoxyl sulfate, a toxin linked to chronic kidney disease.
Bile acid byproducts. Your gut bugs also feast on (and transform) bile acids before they reabsorb and travel back to the liver.
Research is gaining traction on these secondary bile acids, which can affect inflammation and immune function in helpful and harmful ways.
One area of interest is how microbes break down hormones in bile. A recent study from Harvard showed that gut microbes convert corticoid hormones in bile into progestins, which could affect postpartum depression risk. And researchers are exploring the estrobolome — a gut microbial community dedicated to breaking down estrogen into its active form so it can be reabsorbed.
“Depending on the bacteria that you have, more or less can be recirculated back into your blood,” said Beatriz Peñalver Bernabé, PhD, an assistant professor of biomedical engineering and urology at the University of Illinois Chicago. “So you may be producing the same amount of estrogen, but depending on the bacteria you have, the real free estrogen that can bind to your cells may be very different.”
The gut microbiome can also regulate testosterone, with studies showing microbial differences in men with high testosterone vs those with less.
What Patients Can Do Now
Advances in the field of microbiome research — and the related “gut health” wellness craze — have spawned all kinds of new microbiome-based products: Like over-the-counter probiotic supplements and at-home test kits, which let you send a stool sample for analysis to reveal microbiome health and personalized diet recommendations.
But the science behind these tests is still evolving, said Dr. Damman. “The clinical inferences and applications are still pretty limited.”
For most people, the first step to fostering healthier microbial metabolites is much simpler: Diversify your diet.
“A lot of folks are missing that diversity,” Dr. Damman said.
“Eat foods and experiment with foods that you might not eat all the time,” especially fruits, vegetables, nuts, seeds, and beans.
Another strategy: Eat foods with probiotic bacteria. “I view it as an insurance policy,” said Dr. Versalovic, “fortifying my gut with probiotics, with daily yogurt, for example, at breakfast.”
Fermented foods like kimchi and kombucha can also increase microbial diversity and can even contain health-promoting postbiotics, research shows.
As for probiotic supplements, the jury’s still out.
Certain strains of probiotic bacteria may be beneficial for some patients, like those with diarrhea, Crohn’s disease, and irritable bowel syndrome, according to World Gastroenterology Organisation guidelines.
As with other interventions, individual responses can vary. A Stanford study showed that some people with metabolic syndrome improved when taking a probiotic, while others didn’t. Both groups had key differences in gut bacteria and dietary habits.
For best results, such microbiome-based interventions will need to be personalized, experts say. And the technology to do that is coming sooner than you might think.
Microbiome’s Medical Future: ‘We Are on the Cusp of a New Era’
In just a few years, artificial intelligence (AI) models could predict gut microbial composition based on data such as dietary habits and household characteristics, Dr. Kumar said.
Advancements in metabolomics and bioinformatics could soon help physicians and patients personalize their treatment approaches, said Dr. Damman.
One focus will be on fortifying the gut with whatever it lacks.
“In those individuals where certain microbes are missing, (a) how could we add them back potentially in a rational, science-driven way, and (b) maybe some of those factors that the microbes are producing out the other ends, you could give directly,” said Dr. Damman.
For example, multiple companies make butyrate as a dietary supplement, although the research is too early to support widespread use. Another option could be eating something that spurs butyrate production. One small study found that a fiber supplement formulated to increase butyrate levels in the colon reduced participants’ systolic blood pressure by an average of six points.
Another option could be synbiotics, products that combine bacteria and the food source they feed on. “If you just give a diet-based therapy, it is not going to work as much. Because what if that diet needs certain bacteria to have these beneficial metabolites?” said Ashutosh Mangalam, PhD, associate professor of pathology at the University of Iowa Carver College of Medicine, Iowa City.
Dr. Mangalam studies links between bacterial metabolism of phytoestrogens in soy foods and multiple sclerosis (MS) development. He is using AI to understand differences in metabolites in patients with MS vs healthy controls to determine how to target them.
Gut microbial metabolites could also affect disease screening and intervention. What if gut microbe sequencing could predict a pregnant person’s risk of developing depression, something now assessed through simple questionnaires?
“Imagine that your doctor says, ‘Okay, give me a poop sample,’ ” Dr. Bernabé said. “Then they phenotype it, and then they put it in your electronic medical record, and they say, ‘Well, you have high likelihood of having a mood disorder down the line in your pregnancy. Why don’t we directly refer you to a provider now so you can follow up?’ ”
Research is already underway to understand how metabolites might be linked to pregnancy outcomes, complex regional pain syndrome, and anxiety. Researchers are also investigating whether supplementing our diets with things like prebiotic fibers, apple polyphenols, or tomato paste might influence metabolites. And fecal transplants that shift the gut microbiome and metabolites could have potential in diseases like unexplained atherosclerosis, post-COVID syndrome, and hidradenitis suppurativa.
Dr. Hazen’s discovery linking TMAO with cardiovascular risk has already changed clinical practice. A blood TMAO test can help identify patients at risk who may not have traditional risk factors. “Millions have been done,” Dr. Hazen said.
Meanwhile, his drug targeting the TMAO pathway inches closer to clinical trials.
“In an animal model, we elicit improvement in heart failure, renal disease, atherosclerosis, thrombosis, aortic aneurysm, and obesity,” Dr. Hazen said. The first clinical trials will focus on renal disease.
As with any drug, the road to approval takes time. And success is not guaranteed.
But Dr. Hazen for one is optimistic.
“We are on the cusp of a new era,” Dr. Hazen said. “Like when humans first discovered insulin and glucagon were hormones that impact sugar metabolism. We now recognize myriad new ‘hormones’ in the form of gut microbiome metabolites that impact our physiology and susceptibility to diseases.”
A version of this article first appeared on Medscape.com.
Meet your new patients.
You can’t see them, but trillions — maybe quadrillions — of them travel in and out of your practice every day. They’re hungry, mysterious, community-oriented, and small. Very, very small.
They’re the microbes occupying your current patients’ guts.
Someday soon, you’ll prescribe medicine not just for humans but also for these microbes.
“I am convinced in the future our medicine cabinets are going to have not just medications like a statin for treating us, but [also] pills that treat and inhibit an enzyme in our microbes and elicit a health benefit in some chronic disease,” said Stanley Hazen, MD, PhD, co-section head of Preventive Cardiology & Rehabilitation and director of the Center for Microbiome & Human Health at Cleveland Clinic, Cleveland, Ohio.
These trillions of microbes use our food to generate substances called metabolites that can protect or harm our health, with consequences reaching far beyond our gastrointestinal tracts.
Research has linked microbial metabolites to diabetes, cardiovascular disease, liver disease, obesity, high blood pressure, neurological disorders, depression, cancer, and more. Gastroenterologist Christopher Damman, MD, a clinical associate professor at the University of Washington Medical Center, Seattle, calls it a “growing theme” in microbiome science.
Now scientists are developing treatments targeting gut microbial pathways, designed to eliminate the bad metabolites and boost the good metabolites.
One close to human therapeutic intervention is an oral treatment from Dr. Hazen’s lab targeting the metabolite trimethylamine N-oxide (TMAO), a predictor of and contributor to both cardiovascular disease and chronic kidney disease. The drug, which blocks TMAO formation, is nearing clinical trials, Dr. Hazen said.
The advantage is safety. By targeting the microbe instead of, say, an enzyme, the host (your patient) must absorb little if any drug.
Implications for the future of medicine are huge. “Gut microbial pathways contribute to diabetes, obesity, virtually everything,” Dr. Hazen said. “Therapies that target gut microbiome processes will probably even be used for psychiatric disorders within, I’ll say, 10 or 20 years.”
The Science
About 100 trillion strains of bacteria live in our guts. As humans have evolved, so have they.
Between 70% and 90% come from the phyla Firmicutes and Bacteroidetes, with person-to-person variation shaped by genetics, environment, and lifestyle.
“Everyone’s microbiome is subtly different,” said Dr. Hazen. “So the combination of what they’re making is different. All these different biologically active compounds are influencing us in subtly different ways.”
How it works: When you eat, your microbes eat, breaking down food into metabolites that interact with the thin layer of epithelial cells lining your gut. Some can be absorbed through the lining and into your bloodstream, a phenomenon known as “leaky gut.” Once in your blood, they can trigger irritation and inflammation, potentially leading to a wide variety of health issues, from gas and bloating to autoimmune conditions and mood disorders.
“On the other side of the epithelial lining, you have some of the largest concentrations of immune cells,” said Narendra Kumar, PhD, associate professor of pharmaceutical sciences at Texas A&M University, College Station, Texas.
Metabolites can influence how these immune cells work, possibly explaining why each person’s immune system behaves distinctively.
Of the 1000-plus metabolites linked to the gut microbiome, scientists have identified several that matter.
Short-chain fatty acids. When we eat fiber, colon bacteria ferment it into the beneficial short-chain fatty acids acetate, propionate, and butyrate. These bind to receptors in muscle, liver, and fat tissue, affecting the secretion of gut hormones and peptides related to appetite, inflammation, energy expenditure, and fat oxidation.
Butyrate has been linked to health benefits. It supports the integrity of the gut’s lining, stifling pathogenic gut bacteria, fighting cancer-promoting inflammation, and protecting against obesity and diabetes. It can function as a prebiotic, helping beneficial bacteria thrive. And recent studies linked an abundance of butyrate-producing bacteria with reduced bone fracture risk and hospitalization for infectious disease.
TMAO and phenylacetylglutamine. When we eat foods rich in animal proteins — think eggs, milk, fish, and especially red meat — some gut bacteria convert nutrients like choline and L-carnitine into TMAO and phenylalanine into phenylacetylglutamine. Research conducted by Dr. Hazen’s lab and replicated by others has linked both metabolites to heart problems.
In a landmark study from Dr. Hazen’s group, healthy adults who went on to develop coronary artery disease had significantly higher plasma TMAO levels than those who did not wind up with the condition. The association remained strong, even after controlling for risk factors like age, sex, smoking, high blood pressure, and high cholesterol.
In preclinical studies, elevated TMAO enhanced cardiovascular disease. TMAO-producing microbes also accentuated cardiovascular disease phenotypes in mouse models, while blocking these pathways inhibited the phenotypes.
Research suggests TMAO may harm cardiomyocytes (cells that contract and relax the heart) in dozens of ways, such as activating the expression of proteins to promote hypertrophy and fibrosis, decreasing mitochondrial function, and disrupting calcium signaling.
Another study linked phenylacetylglutamine levels to cardiac event risk in patients with heart failure. Recent mechanistic investigations suggest the metabolite alters signaling in a beta-adrenergic receptor involved in our fight-or-flight response, said Hazen.
“It’s like a rheostat on the light switch, a dimmer switch, and it’s what’s called a negative allosteric modulator,” he said. “It’s the first time that this type of behavior has ever been shown to be present for a gut microbial metabolite and a host receptor.”
Tryptophan metabolites. Microbes in your colon can convert the amino acid tryptophan, also found in animal-based foods, into neurotransmitters like serotonin and melatonin.
“The enteric nervous system, the nervous system around the gut, is immense,” said James Versalovic, MD, PhD, professor of pathology and immunology at Baylor College of Medicine, Houston. “The gut-brain axis has become a very fertile area of research.”
Lesser-known tryptophan metabolites — like indole, tryptamine, and indoleethanol — have been linked to benefits like fortifying the gut barrier, promoting the release of glucagon-like peptide 1 to reduce appetite, and protecting the liver from hepatitis. However, indole can also spur the production of indoxyl sulfate, a toxin linked to chronic kidney disease.
Bile acid byproducts. Your gut bugs also feast on (and transform) bile acids before they reabsorb and travel back to the liver.
Research is gaining traction on these secondary bile acids, which can affect inflammation and immune function in helpful and harmful ways.
One area of interest is how microbes break down hormones in bile. A recent study from Harvard showed that gut microbes convert corticoid hormones in bile into progestins, which could affect postpartum depression risk. And researchers are exploring the estrobolome — a gut microbial community dedicated to breaking down estrogen into its active form so it can be reabsorbed.
“Depending on the bacteria that you have, more or less can be recirculated back into your blood,” said Beatriz Peñalver Bernabé, PhD, an assistant professor of biomedical engineering and urology at the University of Illinois Chicago. “So you may be producing the same amount of estrogen, but depending on the bacteria you have, the real free estrogen that can bind to your cells may be very different.”
The gut microbiome can also regulate testosterone, with studies showing microbial differences in men with high testosterone vs those with less.
What Patients Can Do Now
Advances in the field of microbiome research — and the related “gut health” wellness craze — have spawned all kinds of new microbiome-based products: Like over-the-counter probiotic supplements and at-home test kits, which let you send a stool sample for analysis to reveal microbiome health and personalized diet recommendations.
But the science behind these tests is still evolving, said Dr. Damman. “The clinical inferences and applications are still pretty limited.”
For most people, the first step to fostering healthier microbial metabolites is much simpler: Diversify your diet.
“A lot of folks are missing that diversity,” Dr. Damman said.
“Eat foods and experiment with foods that you might not eat all the time,” especially fruits, vegetables, nuts, seeds, and beans.
Another strategy: Eat foods with probiotic bacteria. “I view it as an insurance policy,” said Dr. Versalovic, “fortifying my gut with probiotics, with daily yogurt, for example, at breakfast.”
Fermented foods like kimchi and kombucha can also increase microbial diversity and can even contain health-promoting postbiotics, research shows.
As for probiotic supplements, the jury’s still out.
Certain strains of probiotic bacteria may be beneficial for some patients, like those with diarrhea, Crohn’s disease, and irritable bowel syndrome, according to World Gastroenterology Organisation guidelines.
As with other interventions, individual responses can vary. A Stanford study showed that some people with metabolic syndrome improved when taking a probiotic, while others didn’t. Both groups had key differences in gut bacteria and dietary habits.
For best results, such microbiome-based interventions will need to be personalized, experts say. And the technology to do that is coming sooner than you might think.
Microbiome’s Medical Future: ‘We Are on the Cusp of a New Era’
In just a few years, artificial intelligence (AI) models could predict gut microbial composition based on data such as dietary habits and household characteristics, Dr. Kumar said.
Advancements in metabolomics and bioinformatics could soon help physicians and patients personalize their treatment approaches, said Dr. Damman.
One focus will be on fortifying the gut with whatever it lacks.
“In those individuals where certain microbes are missing, (a) how could we add them back potentially in a rational, science-driven way, and (b) maybe some of those factors that the microbes are producing out the other ends, you could give directly,” said Dr. Damman.
For example, multiple companies make butyrate as a dietary supplement, although the research is too early to support widespread use. Another option could be eating something that spurs butyrate production. One small study found that a fiber supplement formulated to increase butyrate levels in the colon reduced participants’ systolic blood pressure by an average of six points.
Another option could be synbiotics, products that combine bacteria and the food source they feed on. “If you just give a diet-based therapy, it is not going to work as much. Because what if that diet needs certain bacteria to have these beneficial metabolites?” said Ashutosh Mangalam, PhD, associate professor of pathology at the University of Iowa Carver College of Medicine, Iowa City.
Dr. Mangalam studies links between bacterial metabolism of phytoestrogens in soy foods and multiple sclerosis (MS) development. He is using AI to understand differences in metabolites in patients with MS vs healthy controls to determine how to target them.
Gut microbial metabolites could also affect disease screening and intervention. What if gut microbe sequencing could predict a pregnant person’s risk of developing depression, something now assessed through simple questionnaires?
“Imagine that your doctor says, ‘Okay, give me a poop sample,’ ” Dr. Bernabé said. “Then they phenotype it, and then they put it in your electronic medical record, and they say, ‘Well, you have high likelihood of having a mood disorder down the line in your pregnancy. Why don’t we directly refer you to a provider now so you can follow up?’ ”
Research is already underway to understand how metabolites might be linked to pregnancy outcomes, complex regional pain syndrome, and anxiety. Researchers are also investigating whether supplementing our diets with things like prebiotic fibers, apple polyphenols, or tomato paste might influence metabolites. And fecal transplants that shift the gut microbiome and metabolites could have potential in diseases like unexplained atherosclerosis, post-COVID syndrome, and hidradenitis suppurativa.
Dr. Hazen’s discovery linking TMAO with cardiovascular risk has already changed clinical practice. A blood TMAO test can help identify patients at risk who may not have traditional risk factors. “Millions have been done,” Dr. Hazen said.
Meanwhile, his drug targeting the TMAO pathway inches closer to clinical trials.
“In an animal model, we elicit improvement in heart failure, renal disease, atherosclerosis, thrombosis, aortic aneurysm, and obesity,” Dr. Hazen said. The first clinical trials will focus on renal disease.
As with any drug, the road to approval takes time. And success is not guaranteed.
But Dr. Hazen for one is optimistic.
“We are on the cusp of a new era,” Dr. Hazen said. “Like when humans first discovered insulin and glucagon were hormones that impact sugar metabolism. We now recognize myriad new ‘hormones’ in the form of gut microbiome metabolites that impact our physiology and susceptibility to diseases.”
A version of this article first appeared on Medscape.com.
Doing the Best They Can
Our dermatology department is composed of 25 doctors spread across 4 offices. It can be difficult to sustain cohesion so we have a few rituals to help hold us together. One is the morning huddle. This is a stand-up meeting lasting 3-5 minutes at 8:42 a.m. (just before the 8:45 a.m. patients). Led by our staff, huddle is a quick review of the priorities, issues, and celebrations across our department. While enthusiastically celebrating a staff member’s promotion one morning, a patient swung open the exam door and shouted, “What’s going on out here?! I’m sitting here waiting!” before slamming the door closed again. “Well, that was unnecessary,” our morning lead interjected as she went to reprimand him.
His behavior was easily recognizable to any doctor with children. It was an emotional outburst we call a tantrum. Although a graphic of tantrums by age would show a steep curve that drops precipitously after 4-years-old (please God, I hope), it persists throughout life. Even adults have tantrums. After? When I broke my pinky toe saving the family from flaming tornadoes a few weeks ago (I ran into the sofa), I flung the ice bag across the room in frustration. “You’ve a right to be mad,” my wife said returning the ice to where I was elevating my foot. She was spot on, it is understandable that I would be angry. It will be weeks before I can run again. And also my toe was broken. Both things were true.
“Two things are true” is a technique for managing tantrums in toddlers. I first learned of it from Dr. Becky Kennedy, a clinical psychologist specializing in family therapy. She has a popular podcast called “Good Inside” based on her book of the same name. Her approach is to use positive psychology with an emphasis on connecting with children to not only shape behavior, but also to help them learn to manage their emotions. I read her book to level up dad skills and realized many of her principles are applicable to various types of relationships. Instead of viewing behaviors as an end, she instead recommends using them as an opportunity to probe for understanding. Assume they are doing the best they can. When my 4-year-old obstinately refused to go to bed despite the usual colored night lights and bedtime rituals, it seemed she was being a typical tantrum-y toddler. The more I insisted — lights-out! the more she resisted. It wasn’t until I asked why that I learned she was worried that the trash truck was going to come overnight. What seemed like just a behavioral problem, time for bed, was actually an opportunity for her to be seen and for us to connect.
I was finishing up with a patient last week when my medical assistant interrupted to advise my next patient was leaving. I walked out to see her storm into the corridor heading for the exit. “I am sorry, you must be quite frustrated having to wait for me.” “Yes, you don’t respect my time,” she said loudly enough for everyone pretending to not notice. I coaxed her back into the room and sat down. After apologizing for her wait and explaining it was because an urgent patient had been added to my schedule, she calmed down and allowed me to continue. At her previous visit, I had biopsied a firm dermal papule on her upper abdomen that turned out to be metastatic breast cancer. She was treated years ago and believed she was in complete remission. Now she was alone, terrified, and wanted her full appointment with me. Because I was running late, she assumed I wouldn’t have the time for her. It was an opportunity for me to connect with her and help her feel safe. I would have missed that opportunity if I had labeled her as just another angry “Karen” brassly asserting herself.
Dr. Kennedy talks a lot in her book about taking the “Most generous interpretation” of whatever behavioral issue arises. Take the time to validate what they are feeling and empathize as best as we can. Acknowledge that it’s normal to be angry and also these are the truths we have to work with. Two truths commonly appear in these emotional episodes. One, the immutable facts, for example, insurance doesn’t cover that drug, and two, your right to be frustrated by that. Above all, remember you, the doctor, are good inside as is your discourteous patient, disaffected staff member or sometimes mendacious teenager. “All good decisions start with feeling secure and nothing feels more secure than being recognized for the good people we are,” says Dr. Kennedy. True I believe even if we sometimes slam the door.
Dr. Benabio is chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at dermnews@mdedge.com.
Our dermatology department is composed of 25 doctors spread across 4 offices. It can be difficult to sustain cohesion so we have a few rituals to help hold us together. One is the morning huddle. This is a stand-up meeting lasting 3-5 minutes at 8:42 a.m. (just before the 8:45 a.m. patients). Led by our staff, huddle is a quick review of the priorities, issues, and celebrations across our department. While enthusiastically celebrating a staff member’s promotion one morning, a patient swung open the exam door and shouted, “What’s going on out here?! I’m sitting here waiting!” before slamming the door closed again. “Well, that was unnecessary,” our morning lead interjected as she went to reprimand him.
His behavior was easily recognizable to any doctor with children. It was an emotional outburst we call a tantrum. Although a graphic of tantrums by age would show a steep curve that drops precipitously after 4-years-old (please God, I hope), it persists throughout life. Even adults have tantrums. After? When I broke my pinky toe saving the family from flaming tornadoes a few weeks ago (I ran into the sofa), I flung the ice bag across the room in frustration. “You’ve a right to be mad,” my wife said returning the ice to where I was elevating my foot. She was spot on, it is understandable that I would be angry. It will be weeks before I can run again. And also my toe was broken. Both things were true.
“Two things are true” is a technique for managing tantrums in toddlers. I first learned of it from Dr. Becky Kennedy, a clinical psychologist specializing in family therapy. She has a popular podcast called “Good Inside” based on her book of the same name. Her approach is to use positive psychology with an emphasis on connecting with children to not only shape behavior, but also to help them learn to manage their emotions. I read her book to level up dad skills and realized many of her principles are applicable to various types of relationships. Instead of viewing behaviors as an end, she instead recommends using them as an opportunity to probe for understanding. Assume they are doing the best they can. When my 4-year-old obstinately refused to go to bed despite the usual colored night lights and bedtime rituals, it seemed she was being a typical tantrum-y toddler. The more I insisted — lights-out! the more she resisted. It wasn’t until I asked why that I learned she was worried that the trash truck was going to come overnight. What seemed like just a behavioral problem, time for bed, was actually an opportunity for her to be seen and for us to connect.
I was finishing up with a patient last week when my medical assistant interrupted to advise my next patient was leaving. I walked out to see her storm into the corridor heading for the exit. “I am sorry, you must be quite frustrated having to wait for me.” “Yes, you don’t respect my time,” she said loudly enough for everyone pretending to not notice. I coaxed her back into the room and sat down. After apologizing for her wait and explaining it was because an urgent patient had been added to my schedule, she calmed down and allowed me to continue. At her previous visit, I had biopsied a firm dermal papule on her upper abdomen that turned out to be metastatic breast cancer. She was treated years ago and believed she was in complete remission. Now she was alone, terrified, and wanted her full appointment with me. Because I was running late, she assumed I wouldn’t have the time for her. It was an opportunity for me to connect with her and help her feel safe. I would have missed that opportunity if I had labeled her as just another angry “Karen” brassly asserting herself.
Dr. Kennedy talks a lot in her book about taking the “Most generous interpretation” of whatever behavioral issue arises. Take the time to validate what they are feeling and empathize as best as we can. Acknowledge that it’s normal to be angry and also these are the truths we have to work with. Two truths commonly appear in these emotional episodes. One, the immutable facts, for example, insurance doesn’t cover that drug, and two, your right to be frustrated by that. Above all, remember you, the doctor, are good inside as is your discourteous patient, disaffected staff member or sometimes mendacious teenager. “All good decisions start with feeling secure and nothing feels more secure than being recognized for the good people we are,” says Dr. Kennedy. True I believe even if we sometimes slam the door.
Dr. Benabio is chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at dermnews@mdedge.com.
Our dermatology department is composed of 25 doctors spread across 4 offices. It can be difficult to sustain cohesion so we have a few rituals to help hold us together. One is the morning huddle. This is a stand-up meeting lasting 3-5 minutes at 8:42 a.m. (just before the 8:45 a.m. patients). Led by our staff, huddle is a quick review of the priorities, issues, and celebrations across our department. While enthusiastically celebrating a staff member’s promotion one morning, a patient swung open the exam door and shouted, “What’s going on out here?! I’m sitting here waiting!” before slamming the door closed again. “Well, that was unnecessary,” our morning lead interjected as she went to reprimand him.
His behavior was easily recognizable to any doctor with children. It was an emotional outburst we call a tantrum. Although a graphic of tantrums by age would show a steep curve that drops precipitously after 4-years-old (please God, I hope), it persists throughout life. Even adults have tantrums. After? When I broke my pinky toe saving the family from flaming tornadoes a few weeks ago (I ran into the sofa), I flung the ice bag across the room in frustration. “You’ve a right to be mad,” my wife said returning the ice to where I was elevating my foot. She was spot on, it is understandable that I would be angry. It will be weeks before I can run again. And also my toe was broken. Both things were true.
“Two things are true” is a technique for managing tantrums in toddlers. I first learned of it from Dr. Becky Kennedy, a clinical psychologist specializing in family therapy. She has a popular podcast called “Good Inside” based on her book of the same name. Her approach is to use positive psychology with an emphasis on connecting with children to not only shape behavior, but also to help them learn to manage their emotions. I read her book to level up dad skills and realized many of her principles are applicable to various types of relationships. Instead of viewing behaviors as an end, she instead recommends using them as an opportunity to probe for understanding. Assume they are doing the best they can. When my 4-year-old obstinately refused to go to bed despite the usual colored night lights and bedtime rituals, it seemed she was being a typical tantrum-y toddler. The more I insisted — lights-out! the more she resisted. It wasn’t until I asked why that I learned she was worried that the trash truck was going to come overnight. What seemed like just a behavioral problem, time for bed, was actually an opportunity for her to be seen and for us to connect.
I was finishing up with a patient last week when my medical assistant interrupted to advise my next patient was leaving. I walked out to see her storm into the corridor heading for the exit. “I am sorry, you must be quite frustrated having to wait for me.” “Yes, you don’t respect my time,” she said loudly enough for everyone pretending to not notice. I coaxed her back into the room and sat down. After apologizing for her wait and explaining it was because an urgent patient had been added to my schedule, she calmed down and allowed me to continue. At her previous visit, I had biopsied a firm dermal papule on her upper abdomen that turned out to be metastatic breast cancer. She was treated years ago and believed she was in complete remission. Now she was alone, terrified, and wanted her full appointment with me. Because I was running late, she assumed I wouldn’t have the time for her. It was an opportunity for me to connect with her and help her feel safe. I would have missed that opportunity if I had labeled her as just another angry “Karen” brassly asserting herself.
Dr. Kennedy talks a lot in her book about taking the “Most generous interpretation” of whatever behavioral issue arises. Take the time to validate what they are feeling and empathize as best as we can. Acknowledge that it’s normal to be angry and also these are the truths we have to work with. Two truths commonly appear in these emotional episodes. One, the immutable facts, for example, insurance doesn’t cover that drug, and two, your right to be frustrated by that. Above all, remember you, the doctor, are good inside as is your discourteous patient, disaffected staff member or sometimes mendacious teenager. “All good decisions start with feeling secure and nothing feels more secure than being recognized for the good people we are,” says Dr. Kennedy. True I believe even if we sometimes slam the door.
Dr. Benabio is chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at dermnews@mdedge.com.
FDA’s Stricter Regulation of Lab-Developed Tests Faces Lawsuits and Lingering Concerns
The Food and Drug Administration (FDA) plans to scrutinize the safety and efficacy of lab-developed tests — those designed, manufactured, and used in a single laboratory — far more thoroughly in the future.
Under a rule finalized in April, the FDA will treat facilities that develop and use lab tests as manufacturers and regulate tests as medical devices. That means that most lab tests will need an FDA review before going on sale.
The FDA will also impose new quality standards, requiring test manufacturers to report adverse events and create a registry of lab tests under the new rule, which will be phased in over 4 years.
FDA officials have been concerned for years about the reliability of commercial lab tests, which have ballooned into a multibillion-dollar industry.
Consumer groups have long urged the FDA to regulate lab tests more strictly, arguing that the lack of scrutiny allows doctors and patients to be exploited by bad actors such as Theranos, which falsely claimed that its tests could diagnose multiple diseases with a single drop of blood.
“When it comes to some of these tests that doctors are recommending for patients, many doctors are just crossing their fingers and relying on the representation of the company because nobody is checking” to verify a manufacturer’s claims, said Joshua Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Nearly 12,000 Labs Making Medical Tests
Although the FDA estimates there are nearly 12,000 labs manufacturing medical tests, agency officials said they don’t know how many tests are being marketed. The FDA already requires that home test kits marketed directly to consumers, such as those used to detect COVID-19, get clearance from the agency before being sold.
“There’s plenty of time for industry to get its act together to develop the data that it might need to make a premarket application,” said Peter Lurie, MD, PhD, a former associate commissioner at the FDA. In 2015, Dr. Lurie led a report outlining some of the dangers of unregulated lab tests.
For the average physician who orders lab tests, nothing is going to immediately change because of the final rule, said Dr. Lurie, now president of the Center for Science in the Public Interest, a nonprofit consumer watchdog.
“Tomorrow, this will look just the same as it does today,” Dr. Lurie said. “For the next 3 years, the companies will be scurrying behind the scenes to comply with the early stages of implementation. But most of that will be invisible to the average practitioner.”
Dr. Lurie predicted the FDA will focus its scrutiny on tests that pose the greatest potential risk to patients, such as ones used to diagnose serious diseases or guide treatment for life-threatening conditions. “The least significant tests will likely get very limited, if any, scrutiny,” said Dr. Lurie, adding that the FDA will likely issue guidance about how it plans to define low- and high-risk tests. “My suspicion is that it will be probably a small minority of products that are subject to full premarket approval.”
Lab Industry Groups Push Back
But imposing new rules with the potential to affect an industry’s bottom line is no easy task.
The American Clinical Laboratory Association, which represents the lab industry, said in a statement that the FDA rule will “limit access to scores of critical tests, increase healthcare costs, and undermine innovation in new diagnostics.” Another industry group, the Association for Molecular Pathology, has warned of “significant and harmful disruption to laboratory medicine.”
The two associations have filed separate lawsuits, charging that the FDA overstepped the authority granted by Congress. In their lawsuits, groups claim that lab tests are professional services, not manufactured products. The groups noted that the Centers for Medicare & Medicaid Services (CMS) already inspects lab facilities. CMS does not assess the tests’ quality or reliability.
A recent Supreme Court decision could make those lawsuits more likely to succeed, said David Simon, JD, LLM, PhD, an assistant professor of law at the Northeastern University School of Law, Boston, Massachusetts.
In the case of Loper Bright Enterprises v. Raimondo, decided in June, justices overturned a long-standing precedent known as Chevron deference, which required courts to defer to federal agencies when interpreting ambiguous laws. That means that courts no longer have to accept the FDA’s definition of a device, Dr. Simon said.
“Because judges may have more active roles in defining agency authority, federal agencies may have correspondingly less robust roles in policymaking,” Dr. Simon wrote in an editorial coauthored with Michael J. Young, MD, MPhil, of Harvard Medical School, Boston.
The Supreme Court ruling could pressure Congress to more clearly define FDA’s ruling in regulating lab tests, Dr. Simon and Dr. Young wrote.
Members of Congress first introduced a bill to clarify the FDA’s role in regulating lab tests, called the VALID Act, in 2020. The bill stalled and, despite efforts to revive it, still hasn’t passed.
FDA officials have said they remain “open to working with Congress,” noting that any future legislation about lab-developed tests would supersede their current policy.
In an interview, Dr. Simon noted the FDA significantly narrowed the scope of the final rule in response to comments from critics who objected to an earlier version of the policy proposed in 2023. The final rule carves out several categories of tests that won’t need to apply for “premarket review.”
Notably, a “grandfather clause” will allow some lab tests already on the market to continue being sold without undergoing FDA’s premarket review process. In explaining the exemption, FDA officials said they did not want doctors and patients to lose access to tests on which they rely. But Dr. Lurie noted that because the FDA views all these tests as under its jurisdiction, the agency could opt to take a closer look “at a very old device that is causing a problem today.”
The FDA also will exempt tests approved by New York State’s Clinical Laboratory Evaluation Program, which conducts its own stringent reviews. And the FDA will continue to allow hospitals to develop tests for patients within their healthcare system without going through the FDA approval process, if no FDA-approved tests are available.
Hospital-based tests play a critical role in treating infectious diseases, said Amesh Adalja, MD, an infectious diseases specialist and senior scholar at the Johns Hopkins Center for Health Security. For example, a large research hospital treating a patient with cytomegalovirus may need to develop its own test to determine whether the infection is resistant to antiviral drugs, Dr. Adalja said.
“With novel infectious disease outbreaks, researchers are able to move quickly to make diagnostic tests months and months before commercial laboratories are able to get through regulatory processes,” Dr. Adalja said.
To help scientists respond quickly to emergencies, the FDA published special guidance for labs that develop unauthorized lab tests for disease outbreaks.
Medical groups such as the American Hospital Association and Infectious Diseases Society of America remain concerned about the burden of complying with new regulations.
“Many vital tests developed in hospitals and health systems may be subjected to unnecessary and costly paperwork,” said Stacey Hughes, executive vice president of the American Hospital Association, in a statement.
Other groups, such as the American Society of Clinical Oncology, praised the new FDA policy. In comments submitted to the FDA in 2023, the cancer group said it “emphatically supports” requiring lab tests to undergo FDA review.
“We appreciate FDA action to modernize oversight of these tests and are hopeful this rule will increase focus on the need to balance rapid diagnostic innovation with patient safety and access” Everett Vokes, MD, the group’s board chair, said in a statement released after the FDA’s final rule was published.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration (FDA) plans to scrutinize the safety and efficacy of lab-developed tests — those designed, manufactured, and used in a single laboratory — far more thoroughly in the future.
Under a rule finalized in April, the FDA will treat facilities that develop and use lab tests as manufacturers and regulate tests as medical devices. That means that most lab tests will need an FDA review before going on sale.
The FDA will also impose new quality standards, requiring test manufacturers to report adverse events and create a registry of lab tests under the new rule, which will be phased in over 4 years.
FDA officials have been concerned for years about the reliability of commercial lab tests, which have ballooned into a multibillion-dollar industry.
Consumer groups have long urged the FDA to regulate lab tests more strictly, arguing that the lack of scrutiny allows doctors and patients to be exploited by bad actors such as Theranos, which falsely claimed that its tests could diagnose multiple diseases with a single drop of blood.
“When it comes to some of these tests that doctors are recommending for patients, many doctors are just crossing their fingers and relying on the representation of the company because nobody is checking” to verify a manufacturer’s claims, said Joshua Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Nearly 12,000 Labs Making Medical Tests
Although the FDA estimates there are nearly 12,000 labs manufacturing medical tests, agency officials said they don’t know how many tests are being marketed. The FDA already requires that home test kits marketed directly to consumers, such as those used to detect COVID-19, get clearance from the agency before being sold.
“There’s plenty of time for industry to get its act together to develop the data that it might need to make a premarket application,” said Peter Lurie, MD, PhD, a former associate commissioner at the FDA. In 2015, Dr. Lurie led a report outlining some of the dangers of unregulated lab tests.
For the average physician who orders lab tests, nothing is going to immediately change because of the final rule, said Dr. Lurie, now president of the Center for Science in the Public Interest, a nonprofit consumer watchdog.
“Tomorrow, this will look just the same as it does today,” Dr. Lurie said. “For the next 3 years, the companies will be scurrying behind the scenes to comply with the early stages of implementation. But most of that will be invisible to the average practitioner.”
Dr. Lurie predicted the FDA will focus its scrutiny on tests that pose the greatest potential risk to patients, such as ones used to diagnose serious diseases or guide treatment for life-threatening conditions. “The least significant tests will likely get very limited, if any, scrutiny,” said Dr. Lurie, adding that the FDA will likely issue guidance about how it plans to define low- and high-risk tests. “My suspicion is that it will be probably a small minority of products that are subject to full premarket approval.”
Lab Industry Groups Push Back
But imposing new rules with the potential to affect an industry’s bottom line is no easy task.
The American Clinical Laboratory Association, which represents the lab industry, said in a statement that the FDA rule will “limit access to scores of critical tests, increase healthcare costs, and undermine innovation in new diagnostics.” Another industry group, the Association for Molecular Pathology, has warned of “significant and harmful disruption to laboratory medicine.”
The two associations have filed separate lawsuits, charging that the FDA overstepped the authority granted by Congress. In their lawsuits, groups claim that lab tests are professional services, not manufactured products. The groups noted that the Centers for Medicare & Medicaid Services (CMS) already inspects lab facilities. CMS does not assess the tests’ quality or reliability.
A recent Supreme Court decision could make those lawsuits more likely to succeed, said David Simon, JD, LLM, PhD, an assistant professor of law at the Northeastern University School of Law, Boston, Massachusetts.
In the case of Loper Bright Enterprises v. Raimondo, decided in June, justices overturned a long-standing precedent known as Chevron deference, which required courts to defer to federal agencies when interpreting ambiguous laws. That means that courts no longer have to accept the FDA’s definition of a device, Dr. Simon said.
“Because judges may have more active roles in defining agency authority, federal agencies may have correspondingly less robust roles in policymaking,” Dr. Simon wrote in an editorial coauthored with Michael J. Young, MD, MPhil, of Harvard Medical School, Boston.
The Supreme Court ruling could pressure Congress to more clearly define FDA’s ruling in regulating lab tests, Dr. Simon and Dr. Young wrote.
Members of Congress first introduced a bill to clarify the FDA’s role in regulating lab tests, called the VALID Act, in 2020. The bill stalled and, despite efforts to revive it, still hasn’t passed.
FDA officials have said they remain “open to working with Congress,” noting that any future legislation about lab-developed tests would supersede their current policy.
In an interview, Dr. Simon noted the FDA significantly narrowed the scope of the final rule in response to comments from critics who objected to an earlier version of the policy proposed in 2023. The final rule carves out several categories of tests that won’t need to apply for “premarket review.”
Notably, a “grandfather clause” will allow some lab tests already on the market to continue being sold without undergoing FDA’s premarket review process. In explaining the exemption, FDA officials said they did not want doctors and patients to lose access to tests on which they rely. But Dr. Lurie noted that because the FDA views all these tests as under its jurisdiction, the agency could opt to take a closer look “at a very old device that is causing a problem today.”
The FDA also will exempt tests approved by New York State’s Clinical Laboratory Evaluation Program, which conducts its own stringent reviews. And the FDA will continue to allow hospitals to develop tests for patients within their healthcare system without going through the FDA approval process, if no FDA-approved tests are available.
Hospital-based tests play a critical role in treating infectious diseases, said Amesh Adalja, MD, an infectious diseases specialist and senior scholar at the Johns Hopkins Center for Health Security. For example, a large research hospital treating a patient with cytomegalovirus may need to develop its own test to determine whether the infection is resistant to antiviral drugs, Dr. Adalja said.
“With novel infectious disease outbreaks, researchers are able to move quickly to make diagnostic tests months and months before commercial laboratories are able to get through regulatory processes,” Dr. Adalja said.
To help scientists respond quickly to emergencies, the FDA published special guidance for labs that develop unauthorized lab tests for disease outbreaks.
Medical groups such as the American Hospital Association and Infectious Diseases Society of America remain concerned about the burden of complying with new regulations.
“Many vital tests developed in hospitals and health systems may be subjected to unnecessary and costly paperwork,” said Stacey Hughes, executive vice president of the American Hospital Association, in a statement.
Other groups, such as the American Society of Clinical Oncology, praised the new FDA policy. In comments submitted to the FDA in 2023, the cancer group said it “emphatically supports” requiring lab tests to undergo FDA review.
“We appreciate FDA action to modernize oversight of these tests and are hopeful this rule will increase focus on the need to balance rapid diagnostic innovation with patient safety and access” Everett Vokes, MD, the group’s board chair, said in a statement released after the FDA’s final rule was published.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration (FDA) plans to scrutinize the safety and efficacy of lab-developed tests — those designed, manufactured, and used in a single laboratory — far more thoroughly in the future.
Under a rule finalized in April, the FDA will treat facilities that develop and use lab tests as manufacturers and regulate tests as medical devices. That means that most lab tests will need an FDA review before going on sale.
The FDA will also impose new quality standards, requiring test manufacturers to report adverse events and create a registry of lab tests under the new rule, which will be phased in over 4 years.
FDA officials have been concerned for years about the reliability of commercial lab tests, which have ballooned into a multibillion-dollar industry.
Consumer groups have long urged the FDA to regulate lab tests more strictly, arguing that the lack of scrutiny allows doctors and patients to be exploited by bad actors such as Theranos, which falsely claimed that its tests could diagnose multiple diseases with a single drop of blood.
“When it comes to some of these tests that doctors are recommending for patients, many doctors are just crossing their fingers and relying on the representation of the company because nobody is checking” to verify a manufacturer’s claims, said Joshua Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Nearly 12,000 Labs Making Medical Tests
Although the FDA estimates there are nearly 12,000 labs manufacturing medical tests, agency officials said they don’t know how many tests are being marketed. The FDA already requires that home test kits marketed directly to consumers, such as those used to detect COVID-19, get clearance from the agency before being sold.
“There’s plenty of time for industry to get its act together to develop the data that it might need to make a premarket application,” said Peter Lurie, MD, PhD, a former associate commissioner at the FDA. In 2015, Dr. Lurie led a report outlining some of the dangers of unregulated lab tests.
For the average physician who orders lab tests, nothing is going to immediately change because of the final rule, said Dr. Lurie, now president of the Center for Science in the Public Interest, a nonprofit consumer watchdog.
“Tomorrow, this will look just the same as it does today,” Dr. Lurie said. “For the next 3 years, the companies will be scurrying behind the scenes to comply with the early stages of implementation. But most of that will be invisible to the average practitioner.”
Dr. Lurie predicted the FDA will focus its scrutiny on tests that pose the greatest potential risk to patients, such as ones used to diagnose serious diseases or guide treatment for life-threatening conditions. “The least significant tests will likely get very limited, if any, scrutiny,” said Dr. Lurie, adding that the FDA will likely issue guidance about how it plans to define low- and high-risk tests. “My suspicion is that it will be probably a small minority of products that are subject to full premarket approval.”
Lab Industry Groups Push Back
But imposing new rules with the potential to affect an industry’s bottom line is no easy task.
The American Clinical Laboratory Association, which represents the lab industry, said in a statement that the FDA rule will “limit access to scores of critical tests, increase healthcare costs, and undermine innovation in new diagnostics.” Another industry group, the Association for Molecular Pathology, has warned of “significant and harmful disruption to laboratory medicine.”
The two associations have filed separate lawsuits, charging that the FDA overstepped the authority granted by Congress. In their lawsuits, groups claim that lab tests are professional services, not manufactured products. The groups noted that the Centers for Medicare & Medicaid Services (CMS) already inspects lab facilities. CMS does not assess the tests’ quality or reliability.
A recent Supreme Court decision could make those lawsuits more likely to succeed, said David Simon, JD, LLM, PhD, an assistant professor of law at the Northeastern University School of Law, Boston, Massachusetts.
In the case of Loper Bright Enterprises v. Raimondo, decided in June, justices overturned a long-standing precedent known as Chevron deference, which required courts to defer to federal agencies when interpreting ambiguous laws. That means that courts no longer have to accept the FDA’s definition of a device, Dr. Simon said.
“Because judges may have more active roles in defining agency authority, federal agencies may have correspondingly less robust roles in policymaking,” Dr. Simon wrote in an editorial coauthored with Michael J. Young, MD, MPhil, of Harvard Medical School, Boston.
The Supreme Court ruling could pressure Congress to more clearly define FDA’s ruling in regulating lab tests, Dr. Simon and Dr. Young wrote.
Members of Congress first introduced a bill to clarify the FDA’s role in regulating lab tests, called the VALID Act, in 2020. The bill stalled and, despite efforts to revive it, still hasn’t passed.
FDA officials have said they remain “open to working with Congress,” noting that any future legislation about lab-developed tests would supersede their current policy.
In an interview, Dr. Simon noted the FDA significantly narrowed the scope of the final rule in response to comments from critics who objected to an earlier version of the policy proposed in 2023. The final rule carves out several categories of tests that won’t need to apply for “premarket review.”
Notably, a “grandfather clause” will allow some lab tests already on the market to continue being sold without undergoing FDA’s premarket review process. In explaining the exemption, FDA officials said they did not want doctors and patients to lose access to tests on which they rely. But Dr. Lurie noted that because the FDA views all these tests as under its jurisdiction, the agency could opt to take a closer look “at a very old device that is causing a problem today.”
The FDA also will exempt tests approved by New York State’s Clinical Laboratory Evaluation Program, which conducts its own stringent reviews. And the FDA will continue to allow hospitals to develop tests for patients within their healthcare system without going through the FDA approval process, if no FDA-approved tests are available.
Hospital-based tests play a critical role in treating infectious diseases, said Amesh Adalja, MD, an infectious diseases specialist and senior scholar at the Johns Hopkins Center for Health Security. For example, a large research hospital treating a patient with cytomegalovirus may need to develop its own test to determine whether the infection is resistant to antiviral drugs, Dr. Adalja said.
“With novel infectious disease outbreaks, researchers are able to move quickly to make diagnostic tests months and months before commercial laboratories are able to get through regulatory processes,” Dr. Adalja said.
To help scientists respond quickly to emergencies, the FDA published special guidance for labs that develop unauthorized lab tests for disease outbreaks.
Medical groups such as the American Hospital Association and Infectious Diseases Society of America remain concerned about the burden of complying with new regulations.
“Many vital tests developed in hospitals and health systems may be subjected to unnecessary and costly paperwork,” said Stacey Hughes, executive vice president of the American Hospital Association, in a statement.
Other groups, such as the American Society of Clinical Oncology, praised the new FDA policy. In comments submitted to the FDA in 2023, the cancer group said it “emphatically supports” requiring lab tests to undergo FDA review.
“We appreciate FDA action to modernize oversight of these tests and are hopeful this rule will increase focus on the need to balance rapid diagnostic innovation with patient safety and access” Everett Vokes, MD, the group’s board chair, said in a statement released after the FDA’s final rule was published.
A version of this article first appeared on Medscape.com.
Bimekizumab Gains FDA Approval for Psoriatic Arthritis, Axial Spondyloarthritis
The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx; UCB) for adult patients with active psoriatic arthritis (PsA), active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and active ankylosing spondylitis (AS).
The drug, an interleukin (IL)–17A and IL-17F inhibitor, was first approved in October 2023 for treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
“In psoriatic arthritis and across the spectrum of axSpA, clinical study results and real-world experience outside the US have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to 2 years,” said Emmanuel Caeymaex, executive vice president, head of patient impact, and chief commercial officer of UCB in a press release.
The recommended dosage of bimekizumab for adult patients with active PsA, nr-axSpA, or AS is 160 mg by subcutaneous injection every 4 weeks. For patients with PsA and coexistent moderate to severe plaque psoriasis, the dosage is the same as for patients with plaque psoriasis. The dosing for plaque psoriasis is to administer 320 mg (two 160-mg injections) by subcutaneous injection at weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing ≥ 120 kg, consider a dose of 320 mg every 4 weeks after week 16.
PsA Clinical Trials
The approval for PsA was based on data from two phase 3 clinical trials, including 852 participants naive to biologics (BE OPTIMAL) and 400 participants with inadequate response to treatment with one or two tumor necrosis factor (TNF) inhibitors (BE COMPLETE). Both studies met their primary endpoint, 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, as well as ranked secondary endpoints. Secondary endpoints included minimal disease activity (MDA) and Psoriasis Area and Severity Index 100 (complete skin clearance) at week 16.
At 16 weeks:
- About 44% of both the biologic-naive (189 of 431) and TNF inhibitor–resistant (116 of 267) groups receiving bimekizumab achieved ACR50 response, compared with 10% (28 of 281) and 7% (9 of 133) receiving placebo, respectively.
- About 45% of all patients treated with bimekizumab achieved MDA.
- Nearly 60% of TNF inhibitor–resistant patients had complete skin clearance.
These responses generally were sustained for 1 year. The most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infection.
NR-axSpA and AS Clinical Trials
The approval for active nr-axSpA and active AS was based on data from two clinical studies, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Both studies met their primary endpoint, 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks.
Key findings included:
- In nr-axSpA patients, 47.7% (61 of 128) receiving bimekizumab achieved ASAS40 at week 16, compared with 21.4% (27 of 126) receiving placebo.
- In AS patients, 44.8% (99 of 221) in the bimekizumab group achieved ASAS40 response at week 16 vs 22.5% (25 of 111) receiving placebo.
- At 1 year in both groups, 60% treated with bimekizumab achieved an Ankylosing Spondylitis Disease Activity Score < 2.1.
In nr-axSpA, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsillitis, increase in transaminase, and urinary tract infection. In AS, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection-site pain, rash, and vulvovaginal mycotic infection.
Bimekizumab was approved by the European Commission for the same rheumatologic indications in June 2023.
Bimekizumab is currently available to eligible patients in the United States, according to the press release.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx; UCB) for adult patients with active psoriatic arthritis (PsA), active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and active ankylosing spondylitis (AS).
The drug, an interleukin (IL)–17A and IL-17F inhibitor, was first approved in October 2023 for treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
“In psoriatic arthritis and across the spectrum of axSpA, clinical study results and real-world experience outside the US have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to 2 years,” said Emmanuel Caeymaex, executive vice president, head of patient impact, and chief commercial officer of UCB in a press release.
The recommended dosage of bimekizumab for adult patients with active PsA, nr-axSpA, or AS is 160 mg by subcutaneous injection every 4 weeks. For patients with PsA and coexistent moderate to severe plaque psoriasis, the dosage is the same as for patients with plaque psoriasis. The dosing for plaque psoriasis is to administer 320 mg (two 160-mg injections) by subcutaneous injection at weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing ≥ 120 kg, consider a dose of 320 mg every 4 weeks after week 16.
PsA Clinical Trials
The approval for PsA was based on data from two phase 3 clinical trials, including 852 participants naive to biologics (BE OPTIMAL) and 400 participants with inadequate response to treatment with one or two tumor necrosis factor (TNF) inhibitors (BE COMPLETE). Both studies met their primary endpoint, 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, as well as ranked secondary endpoints. Secondary endpoints included minimal disease activity (MDA) and Psoriasis Area and Severity Index 100 (complete skin clearance) at week 16.
At 16 weeks:
- About 44% of both the biologic-naive (189 of 431) and TNF inhibitor–resistant (116 of 267) groups receiving bimekizumab achieved ACR50 response, compared with 10% (28 of 281) and 7% (9 of 133) receiving placebo, respectively.
- About 45% of all patients treated with bimekizumab achieved MDA.
- Nearly 60% of TNF inhibitor–resistant patients had complete skin clearance.
These responses generally were sustained for 1 year. The most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infection.
NR-axSpA and AS Clinical Trials
The approval for active nr-axSpA and active AS was based on data from two clinical studies, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Both studies met their primary endpoint, 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks.
Key findings included:
- In nr-axSpA patients, 47.7% (61 of 128) receiving bimekizumab achieved ASAS40 at week 16, compared with 21.4% (27 of 126) receiving placebo.
- In AS patients, 44.8% (99 of 221) in the bimekizumab group achieved ASAS40 response at week 16 vs 22.5% (25 of 111) receiving placebo.
- At 1 year in both groups, 60% treated with bimekizumab achieved an Ankylosing Spondylitis Disease Activity Score < 2.1.
In nr-axSpA, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsillitis, increase in transaminase, and urinary tract infection. In AS, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection-site pain, rash, and vulvovaginal mycotic infection.
Bimekizumab was approved by the European Commission for the same rheumatologic indications in June 2023.
Bimekizumab is currently available to eligible patients in the United States, according to the press release.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx; UCB) for adult patients with active psoriatic arthritis (PsA), active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and active ankylosing spondylitis (AS).
The drug, an interleukin (IL)–17A and IL-17F inhibitor, was first approved in October 2023 for treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
“In psoriatic arthritis and across the spectrum of axSpA, clinical study results and real-world experience outside the US have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to 2 years,” said Emmanuel Caeymaex, executive vice president, head of patient impact, and chief commercial officer of UCB in a press release.
The recommended dosage of bimekizumab for adult patients with active PsA, nr-axSpA, or AS is 160 mg by subcutaneous injection every 4 weeks. For patients with PsA and coexistent moderate to severe plaque psoriasis, the dosage is the same as for patients with plaque psoriasis. The dosing for plaque psoriasis is to administer 320 mg (two 160-mg injections) by subcutaneous injection at weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing ≥ 120 kg, consider a dose of 320 mg every 4 weeks after week 16.
PsA Clinical Trials
The approval for PsA was based on data from two phase 3 clinical trials, including 852 participants naive to biologics (BE OPTIMAL) and 400 participants with inadequate response to treatment with one or two tumor necrosis factor (TNF) inhibitors (BE COMPLETE). Both studies met their primary endpoint, 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, as well as ranked secondary endpoints. Secondary endpoints included minimal disease activity (MDA) and Psoriasis Area and Severity Index 100 (complete skin clearance) at week 16.
At 16 weeks:
- About 44% of both the biologic-naive (189 of 431) and TNF inhibitor–resistant (116 of 267) groups receiving bimekizumab achieved ACR50 response, compared with 10% (28 of 281) and 7% (9 of 133) receiving placebo, respectively.
- About 45% of all patients treated with bimekizumab achieved MDA.
- Nearly 60% of TNF inhibitor–resistant patients had complete skin clearance.
These responses generally were sustained for 1 year. The most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infection.
NR-axSpA and AS Clinical Trials
The approval for active nr-axSpA and active AS was based on data from two clinical studies, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Both studies met their primary endpoint, 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks.
Key findings included:
- In nr-axSpA patients, 47.7% (61 of 128) receiving bimekizumab achieved ASAS40 at week 16, compared with 21.4% (27 of 126) receiving placebo.
- In AS patients, 44.8% (99 of 221) in the bimekizumab group achieved ASAS40 response at week 16 vs 22.5% (25 of 111) receiving placebo.
- At 1 year in both groups, 60% treated with bimekizumab achieved an Ankylosing Spondylitis Disease Activity Score < 2.1.
In nr-axSpA, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsillitis, increase in transaminase, and urinary tract infection. In AS, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection-site pain, rash, and vulvovaginal mycotic infection.
Bimekizumab was approved by the European Commission for the same rheumatologic indications in June 2023.
Bimekizumab is currently available to eligible patients in the United States, according to the press release.
A version of this article first appeared on Medscape.com.
Muscle Relaxants for Chronic Pain: Where Is the Greatest Evidence?
TOPLINE:
The long-term use of muscle relaxants may benefit patients with painful spasms or cramps and neck pain, according to a systematic review of clinical studies, but they do not appear to be beneficial for low back pain, fibromyalgia, or headaches and can have adverse effects such as sedation and dry mouth.
METHODOLOGY:
- Researchers conducted a systematic review to evaluate the effectiveness of long-term use (≥ 4 weeks) of muscle relaxants for chronic pain lasting ≥ 3 months.
- They identified 30 randomized clinical trials involving 1314 patients and 14 cohort studies involving 1168 patients, grouped according to the categories of low back pain, fibromyalgia, painful cramps or spasticity, headaches, and other syndromes.
- Baclofen, tizanidine, cyclobenzaprine, eperisone, quinine, carisoprodol, orphenadrine, chlormezanone, and methocarbamol were the muscle relaxants assessed in comparison with placebo, other treatments, or untreated individuals.
TAKEAWAY:
- The long-term use of muscle relaxants reduced pain intensity in those with painful spasms or cramps and neck pain. Baclofen, orphenadrine, carisoprodol, and methocarbamol improved cramp frequency, while the use of eperisone and chlormezanone improved neck pain and enhanced the quality of sleep, respectively, in those with neck osteoarthritis.
- While some studies suggested that muscle relaxants reduced pain intensity in those with back pain and fibromyalgia, between-group differences were not observed. The benefits seen with some medications diminished after their discontinuation.
- Despite tizanidine improving pain severity in headaches, 25% participants dropped out owing to adverse effects. Although certain muscle relaxants demonstrated pain relief, others did not.
- The most common adverse effects of muscle relaxants were somnolence and dry mouth. Other adverse events included vomiting, diarrhea, nausea, weakness, and constipation.
IN PRACTICE:
“For patients already prescribed long-term SMRs [skeletal muscle relaxants], interventions are needed to assist clinicians to engage in shared decision-making with patients about deprescribing SMRs. This may be particularly true for older patients for whom risks of adverse events may be greater,” the authors wrote. “Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.”
SOURCE:
The study, led by Benjamin J. Oldfield, MD, MHS, Yale School of Medicine, New Haven, Connecticut, was published online on September 19, 2024, in JAMA Network Open
LIMITATIONS:
This systematic review was limited to publications written in English, Spanish, and Italian language, potentially excluding studies from other regions. Variations in clinical sites, definitions of pain syndromes, medications, and durations of therapy prevented the possibility of conducting meta-analyses. Only quantitative studies were included, excluding valuable insights into patient experiences offered by qualitative studies.
DISCLOSURES:
The study was supported by the National Institute on Drug Abuse. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
The long-term use of muscle relaxants may benefit patients with painful spasms or cramps and neck pain, according to a systematic review of clinical studies, but they do not appear to be beneficial for low back pain, fibromyalgia, or headaches and can have adverse effects such as sedation and dry mouth.
METHODOLOGY:
- Researchers conducted a systematic review to evaluate the effectiveness of long-term use (≥ 4 weeks) of muscle relaxants for chronic pain lasting ≥ 3 months.
- They identified 30 randomized clinical trials involving 1314 patients and 14 cohort studies involving 1168 patients, grouped according to the categories of low back pain, fibromyalgia, painful cramps or spasticity, headaches, and other syndromes.
- Baclofen, tizanidine, cyclobenzaprine, eperisone, quinine, carisoprodol, orphenadrine, chlormezanone, and methocarbamol were the muscle relaxants assessed in comparison with placebo, other treatments, or untreated individuals.
TAKEAWAY:
- The long-term use of muscle relaxants reduced pain intensity in those with painful spasms or cramps and neck pain. Baclofen, orphenadrine, carisoprodol, and methocarbamol improved cramp frequency, while the use of eperisone and chlormezanone improved neck pain and enhanced the quality of sleep, respectively, in those with neck osteoarthritis.
- While some studies suggested that muscle relaxants reduced pain intensity in those with back pain and fibromyalgia, between-group differences were not observed. The benefits seen with some medications diminished after their discontinuation.
- Despite tizanidine improving pain severity in headaches, 25% participants dropped out owing to adverse effects. Although certain muscle relaxants demonstrated pain relief, others did not.
- The most common adverse effects of muscle relaxants were somnolence and dry mouth. Other adverse events included vomiting, diarrhea, nausea, weakness, and constipation.
IN PRACTICE:
“For patients already prescribed long-term SMRs [skeletal muscle relaxants], interventions are needed to assist clinicians to engage in shared decision-making with patients about deprescribing SMRs. This may be particularly true for older patients for whom risks of adverse events may be greater,” the authors wrote. “Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.”
SOURCE:
The study, led by Benjamin J. Oldfield, MD, MHS, Yale School of Medicine, New Haven, Connecticut, was published online on September 19, 2024, in JAMA Network Open
LIMITATIONS:
This systematic review was limited to publications written in English, Spanish, and Italian language, potentially excluding studies from other regions. Variations in clinical sites, definitions of pain syndromes, medications, and durations of therapy prevented the possibility of conducting meta-analyses. Only quantitative studies were included, excluding valuable insights into patient experiences offered by qualitative studies.
DISCLOSURES:
The study was supported by the National Institute on Drug Abuse. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
The long-term use of muscle relaxants may benefit patients with painful spasms or cramps and neck pain, according to a systematic review of clinical studies, but they do not appear to be beneficial for low back pain, fibromyalgia, or headaches and can have adverse effects such as sedation and dry mouth.
METHODOLOGY:
- Researchers conducted a systematic review to evaluate the effectiveness of long-term use (≥ 4 weeks) of muscle relaxants for chronic pain lasting ≥ 3 months.
- They identified 30 randomized clinical trials involving 1314 patients and 14 cohort studies involving 1168 patients, grouped according to the categories of low back pain, fibromyalgia, painful cramps or spasticity, headaches, and other syndromes.
- Baclofen, tizanidine, cyclobenzaprine, eperisone, quinine, carisoprodol, orphenadrine, chlormezanone, and methocarbamol were the muscle relaxants assessed in comparison with placebo, other treatments, or untreated individuals.
TAKEAWAY:
- The long-term use of muscle relaxants reduced pain intensity in those with painful spasms or cramps and neck pain. Baclofen, orphenadrine, carisoprodol, and methocarbamol improved cramp frequency, while the use of eperisone and chlormezanone improved neck pain and enhanced the quality of sleep, respectively, in those with neck osteoarthritis.
- While some studies suggested that muscle relaxants reduced pain intensity in those with back pain and fibromyalgia, between-group differences were not observed. The benefits seen with some medications diminished after their discontinuation.
- Despite tizanidine improving pain severity in headaches, 25% participants dropped out owing to adverse effects. Although certain muscle relaxants demonstrated pain relief, others did not.
- The most common adverse effects of muscle relaxants were somnolence and dry mouth. Other adverse events included vomiting, diarrhea, nausea, weakness, and constipation.
IN PRACTICE:
“For patients already prescribed long-term SMRs [skeletal muscle relaxants], interventions are needed to assist clinicians to engage in shared decision-making with patients about deprescribing SMRs. This may be particularly true for older patients for whom risks of adverse events may be greater,” the authors wrote. “Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.”
SOURCE:
The study, led by Benjamin J. Oldfield, MD, MHS, Yale School of Medicine, New Haven, Connecticut, was published online on September 19, 2024, in JAMA Network Open
LIMITATIONS:
This systematic review was limited to publications written in English, Spanish, and Italian language, potentially excluding studies from other regions. Variations in clinical sites, definitions of pain syndromes, medications, and durations of therapy prevented the possibility of conducting meta-analyses. Only quantitative studies were included, excluding valuable insights into patient experiences offered by qualitative studies.
DISCLOSURES:
The study was supported by the National Institute on Drug Abuse. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Patient Navigators in Rheumatology Set to Expand in Importance, Scope With New Medicare Codes
When a large rheumatology clinic in Richmond, Virginia, heard that Medicare would be reimbursing patient navigators, they decided to launch their own virtual navigator program.
“We read about it and felt like it was the perfect representation of what we were already trying to do,” said Blake Wehman, founder and CEO of Remission Medical, which offers virtual diagnosis and longitudinal care in rheumatology.
Mr. Wehman has plans to start submitting for these principal illness navigation (PIN) codes in 2025.
The Centers for Medicare & Medicaid Services (CMS) in 2024 began paying navigators who assist Medicare patients with high-risk conditions, which could include rheumatologic diseases. “The codes are not limited to a specific set of diagnoses; rather, the definition of a serious, high-risk condition is dependent on clinical judgment,” the agency clarified.
CMS established this provision in the CY 2024 Physician Fee Schedule final rule.
Reimbursing patient navigators is long overdue, noted Edith Williams, PhD, MS, director of the Center for Community Health and Prevention and founding director of the Office of Health Equity Research at the University of Rochester in New York. “It’s something our patients need. It’s something that the science is telling us can impact outcomes as an adjunct to clinical care,” she said. 
Dr. Williams said the new CMS codes “got our departments talking about what this policy is and how it would translate into patient care.”
The codes apply when navigators are assigned to support patients with high-risk conditions who need assistance connecting with clinical and other resources, including any unmet social determinants of health needs, or in diagnosis or treatment of their medical problems.
“Having a navigator by their side to help get through all the clinical and administrative challenges gives people an advocate and a partner who is with them and their families every step of the way to help make the journey easier,” said a CMS spokesperson.
Not all navigator programs may qualify for the new codes. Some are supported by grants and don’t bill patient insurance. However, they all share a common goal: to guide patients through the healthcare continuum and assist with appointments and medication adherence.
Identifying ‘Root Causes’ of Barriers
Navigators represent a wide variety of backgrounds, ranging from healthcare professionals to students or even patients themselves. They generally don’t provide medical advice. “However, we are responsible for making sure our patients and their families are educated and aware, then assist with guidance on their path,” said Katie Costillo, BSW, CPPN, patient navigator and program manager with the Lupus Foundation of America, Heartland Region.
“Training and experience in engaging and building rapport is essential to assisting patients overcome obstacles that limit their access to healthcare,” she said. Narrowing down with patients the root causes of their barriers and then identifying appropriate and available community resources is key.
Studies have demonstrated the effectiveness of adding a navigator to a rheumatology patient’s care plan. In one study, a group of Boston researchers determined that navigators played a useful role in reducing adherence barriers to oral disease-modifying antirheumatic drugs. The navigators uncovered several concerns among 107 rheumatology patients, including fear of adverse events and medication effectiveness.
They also helped to facilitate patient-physician communication, developed strategies to improve medication adherence, and provided medication and diagnosis education. Patients reported satisfaction with the navigator experience.
A study Dr. Williams coauthored that examined behavioral interventions to support African American women with systemic lupus erythematosus found that patient navigator participants had superior coping scores, compared with those engaged in peer-to-peer methodology and patient support groups.
“We had a lot of success with the mentorship program, too,” Dr. Williams said. Navigator services, however, offer more one-on-one attention, “and it’s more tailored to what the person needs rather than the set curriculum that the mentors delivered to their mentees.”
Supporting Patients With Lupus
Ideally, navigators should be able to relate to patients and know what they’re going through, Dr. Williams said. This is someone whom the patient can trust and depend on. “That’s where the benefit of having someone who is also a patient lies because they’re ultimately relatable to other patients. But different institutions have taken different approaches to this.”
Some programs focus on specific rheumatologic conditions. The Lupus Foundation of America, for example, established patient navigator programs to assist patients with lupus in four markets across the country.
The Heartland patient navigator program is available for all patients with lupus within its region, which includes Kansas, Missouri, and central and southern Illinois. As a navigator, Ms. Costillo has been assisting patients since 2022. In 2023, she began meeting with patients at the Washington University Lupus Clinic (WULC) in St. Louis, Missouri.
Navigators work directly with patients before and after their appointment to ensure follow-up and reduce missed appointments. “They help lupus patients connect with community services and overcoming barriers to access and care. The goal of this position is to improve overall disease management, which results in better health outcomes,” Ms. Costillo said.
Since its inception, the patient navigator program at WULC has shown a decrease in patient no-call no-shows and an increase in requests to reschedule as opposed to not showing up for their scheduled appointment, based on history.
Patients have reported fewer barriers to transportation and improvement in access to resources, support, and disease education. “Our patients have also stated [that] meeting with the navigator during their appointments has helped them to feel heard, understood, and supported,” Ms. Costillo said.
Navigator Work Is Not Without Challenges
A total of 90% of patients with lupus are women, and women of color are two to three times more likely to develop lupus in their lifetime.
“Based on socioeconomic statistics, lupus patients are in a demographic that is commonly underserved, underfunded, and often overlooked. Finding appropriate local community resources for a patient who must choose between feeding her family or paying for transportation to multiple physician appointments is a common problem,” Ms. Costillo said.
Much of the assistance that became available during the COVID pandemic is starting to disappear. “With the rising costs of daily living, we are having to find creative and alternative ways to break down barriers and find support to fill those gaps,” she continued.
Getting insurance coverage of patients is another challenge. Many patients with lupus will be prescribed a treatment that insurance refuses to cover even after the physician disputes it.
Additionally, many patients with lupus are unable to work to support their family. A majority who apply for Social Security Disability Insurance are denied on their first and second attempts, “requiring multiple hearings and pages of documentation from their physicians,” Ms. Costillo said.
Students Serve as Navigators
One inner-city program is seeking to increase access to healthcare services to patients with lupus and lupus nephritis in underserved communities. In 2021, SUNY Downstate Health Sciences University in New York City, in partnership with the Brooklyn Free Clinic and Brooklyn Health Disparities Center, launched a program to teach navigator skills to second-year medical students.
The students assist patients at the Arthritis Clinic at University Hospital at Downstate. “Many of our patients have either low medical literacy or difficulty with English. Many of them are immigrants,” said Ellen M. Ginzler, MD, MPH, SUNY Downstate’s professor emerita and former vice-chair for research and rheumatology division chief.
Dr. Ginzler sought out navigator candidates who showed a strong interest in working with underserved patients with complicated, severe disease who struggled with keeping appointments or adhering to medication regimens. The program also gave preference to students fluent in other languages such as Spanish.
All these efforts have generated improvements in care.
Assessing the program’s effectiveness in a cross-sectional study, Dr. Ginzler and colleagues reported that 94% of navigators were able to schedule appointments and 87% assisted with prescriptions. Navigators also had high success rates in answering medical questions, getting in touch with a patient’s doctor, and reminding patients of medical appointments.
Medical student Jeremy Wilson, a coauthor of the study, served as a navigator for a woman with lupus and scleroderma for many years, along with other comorbidities.
Mr. Wilson went above and beyond for this patient, helping to secure social services supports that included accompanying her to clinic visits and serving as her advocate. “She found an enormous difference in how she was treated when she went to these clinics because the doctors in those clinics took her much more seriously,” Dr. Ginzler said. Mr. Wilson ran interference to secure clinic appointments and worked with the patient’s rheumatology fellow in the clinic to get approval for medications.
Mr. Wilson and the patient formed a great bond. “It not only helped the patient, but it helped Jeremy tremendously in terms of how he felt about his medical career,” Dr. Ginzler said.
The program has since expanded to include patients with other rheumatic diseases, such as rheumatoid arthritis and psoriatic arthritis, and also offers navigator services in dermatology.
A total of 21 students to date have completed the second year of the program. “We’ve just selected eight more,” Dr. Ginzler said. Some of the students continue to do the program in their third or even fourth year as they’re applying for residencies.
A student-run, unpublished survey of nine students in the SUNY program found that all nine reported high confidence in identifying social factors that impact patient health and well-being, compared with four who reported high confidence prior to starting the program. “Additionally, students reported increased confidence in providing comprehensive care in rheumatology and dermatology, and interdisciplinary collaboration,” study author Alejandra K. Moncayo, MPH, and colleagues wrote.
When Navigators Go Virtual
Remission Medical offers its navigator service through its own standalone virtual clinic.
Pain associated with rheumatologic conditions increases the urgency to see a doctor. The goal of the virtual RemissionNavigator program is to meet rheumatology patients where they live, to bridge care gaps and reduce wait times, said Mr. Wehman.
RemissionNavigator accomplishes this through video visits and unlimited texting to its network of board-certified rheumatologists or rheumatology-focused advanced practice providers. Experts can answer questions about why labs are ordered, why a patient may have received a certain diagnosis, or provide detailed explanations of a rheumatic condition.
“There are instances where improvement for the patient means waiting a couple days for us versus 45 days for their brick-and-mortar choice,” Mr. Wehman said.
The program currently has 36 subscribers to Remission’s services, which include navigation. “We have 15 providers in a blend of employed and contracted relationships with Remission,” Mr. Wehman said.
Even in its infancy, the navigator program has produced some success stories. “We had a patient tell us that thanks to us, he was seen faster, found relief immediately through our diagnosis and prescription of methotrexate, felt better at work, lost weight, and was happier in general,” Mr. Wehman said.
Another patient was making monthly, 90-minute trips to Richmond for infusion services. Through the virtual program’s assistance, she is now receiving care from home and can get her monthly infusions at a local clinic.
Ultimately, the goal is to help rheumatology move into an era of value-based care where the transition from fee-for-service to per patient will enable optimized care models and better accessibility, Mr. Wehman said. “It will not happen overnight, but every day we work toward this future.”
VA Targets Rheumatology Care
The Department of Veterans Affairs (VA) has also explored the use of navigator services in rheumatology, including virtual services.
VA uses an integrated, interdisciplinary model that manages each veteran’s individual healthcare needs through a coordinated effort among providers, nurses, social workers, pharmacists, and other health professionals, according to VA press secretary Terrence Hayes.
Care coordination may include supporting scheduling appointments, managing chronic conditions, and coordinating care across different medical departments. “This coordination is particularly important in managing complex rheumatologic conditions, where multiple providers may be involved,” Mr. Hayes said.
Additionally, VA has launched a national telerheumatology initiative to improve access to rheumatology providers in rural areas. The initiative will assist veterans in understanding the telehealth system, navigating appointments, and ensuring they have the necessary technology for virtual consultations.
“It will also facilitate communication between rheumatologists, primary care providers, and other specialists, ensuring that all team members are aligned in their approach to the veteran’s care,” Mr. Hayes said.
Who Will Take Advantage of New Codes?
Currently, Remission Medical operates on a cash-pay model, but the company intends to transition to insurance-based coverage in 2025.
Remission Medical also partners directly with preexisting healthcare systems and clinics such as Sentara Health and OrthoVirginia, where a PIN program, powered by Remission Medical’s virtual rheumatology network, may be explored as well.
The company offers its partners synchronous virtual visits and e-consults. It’s likely that these larger organizations will explore coverage for navigator services for Medicare and private insurance. “We can be there to support them as they decide to implement this,” Mr. Wehman said.
Taking advantage of CMS’s navigator PIN codes is an eventual goal. Remission Medical has not submitted the codes yet, “but we do intend to as we continue to grow our membership count,” Mr. Wehman said. “We hope to provide coverage for most of the US and submit the codes to reimbursement by early to mid-2025.”
In terms of reimbursement, the VA operates under a different payment model than Medicare or private insurance, focusing on providing integrated care within the VA system rather than reimbursing for specific services such as patient navigation.
While the SUNY clinic takes care of Medicare patients, it’s unlikely that the new CMS codes for navigators would apply to medical students. Students get paid a monthly stipend for doing navigator work. “There’s a policy about what students can get paid, and how many hours they can work,” Dr. Ginzler clarified.
The SUNY Downstate and Lupus Foundation navigator programs rely on grants to sustain their services. Aurinia Pharmaceuticals has funded both programs, and the SUNY program received an additional grant from Janssen to expand its offerings.
Because it’s grant funded, the navigator position at the Lupus Foundation does not bill patient insurance, Ms. Costillo explained.
Navigator Work Requires Training
Before they start working with patients, navigators often go through a vetting or training process. At Remission Medical, a clinical leadership team does a synchronous interview, background check, and CV review of its potential navigators.
Even before she became a navigator, Ms. Costillo had a strong baseline education in this work. She has a bachelor’s degree in social work and 15 years of experience in social services working with disabled, vulnerable, and underserved populations. Some of her fellow navigators at the Lupus Foundation of America also have degrees in social work.
Ms. Costillo underwent training with the Patient-Centered Education & Research Institute to become a certified professional patient navigator. Her name is on the national registry. The curriculum covered various aspects of medical care such as patient and care team interactions and communications, health and clinical knowledge, patient care coordination and resources, and using evidence-based approaches.
“For our lupus patients, it is essential that navigators understand the disease and the impact on patients and families, treatments available and those in the pipelines, and also the ins and outs of various insurance options,” Ms. Costillo said.
Mr. Wehman, Dr. Williams, and Ms. Costillo reported no disclosures. Dr. Ginzler has been a consultant for Aurinia Pharmaceuticals.
A version of this article first appeared on Medscape.com.
When a large rheumatology clinic in Richmond, Virginia, heard that Medicare would be reimbursing patient navigators, they decided to launch their own virtual navigator program.
“We read about it and felt like it was the perfect representation of what we were already trying to do,” said Blake Wehman, founder and CEO of Remission Medical, which offers virtual diagnosis and longitudinal care in rheumatology.
Mr. Wehman has plans to start submitting for these principal illness navigation (PIN) codes in 2025.
The Centers for Medicare & Medicaid Services (CMS) in 2024 began paying navigators who assist Medicare patients with high-risk conditions, which could include rheumatologic diseases. “The codes are not limited to a specific set of diagnoses; rather, the definition of a serious, high-risk condition is dependent on clinical judgment,” the agency clarified.
CMS established this provision in the CY 2024 Physician Fee Schedule final rule.
Reimbursing patient navigators is long overdue, noted Edith Williams, PhD, MS, director of the Center for Community Health and Prevention and founding director of the Office of Health Equity Research at the University of Rochester in New York. “It’s something our patients need. It’s something that the science is telling us can impact outcomes as an adjunct to clinical care,” she said.
Dr. Williams said the new CMS codes “got our departments talking about what this policy is and how it would translate into patient care.”
The codes apply when navigators are assigned to support patients with high-risk conditions who need assistance connecting with clinical and other resources, including any unmet social determinants of health needs, or in diagnosis or treatment of their medical problems.
“Having a navigator by their side to help get through all the clinical and administrative challenges gives people an advocate and a partner who is with them and their families every step of the way to help make the journey easier,” said a CMS spokesperson.
Not all navigator programs may qualify for the new codes. Some are supported by grants and don’t bill patient insurance. However, they all share a common goal: to guide patients through the healthcare continuum and assist with appointments and medication adherence.
Identifying ‘Root Causes’ of Barriers
Navigators represent a wide variety of backgrounds, ranging from healthcare professionals to students or even patients themselves. They generally don’t provide medical advice. “However, we are responsible for making sure our patients and their families are educated and aware, then assist with guidance on their path,” said Katie Costillo, BSW, CPPN, patient navigator and program manager with the Lupus Foundation of America, Heartland Region.
“Training and experience in engaging and building rapport is essential to assisting patients overcome obstacles that limit their access to healthcare,” she said. Narrowing down with patients the root causes of their barriers and then identifying appropriate and available community resources is key.
Studies have demonstrated the effectiveness of adding a navigator to a rheumatology patient’s care plan. In one study, a group of Boston researchers determined that navigators played a useful role in reducing adherence barriers to oral disease-modifying antirheumatic drugs. The navigators uncovered several concerns among 107 rheumatology patients, including fear of adverse events and medication effectiveness.
They also helped to facilitate patient-physician communication, developed strategies to improve medication adherence, and provided medication and diagnosis education. Patients reported satisfaction with the navigator experience.
A study Dr. Williams coauthored that examined behavioral interventions to support African American women with systemic lupus erythematosus found that patient navigator participants had superior coping scores, compared with those engaged in peer-to-peer methodology and patient support groups.
“We had a lot of success with the mentorship program, too,” Dr. Williams said. Navigator services, however, offer more one-on-one attention, “and it’s more tailored to what the person needs rather than the set curriculum that the mentors delivered to their mentees.”
Supporting Patients With Lupus
Ideally, navigators should be able to relate to patients and know what they’re going through, Dr. Williams said. This is someone whom the patient can trust and depend on. “That’s where the benefit of having someone who is also a patient lies because they’re ultimately relatable to other patients. But different institutions have taken different approaches to this.”
Some programs focus on specific rheumatologic conditions. The Lupus Foundation of America, for example, established patient navigator programs to assist patients with lupus in four markets across the country.
The Heartland patient navigator program is available for all patients with lupus within its region, which includes Kansas, Missouri, and central and southern Illinois. As a navigator, Ms. Costillo has been assisting patients since 2022. In 2023, she began meeting with patients at the Washington University Lupus Clinic (WULC) in St. Louis, Missouri.
Navigators work directly with patients before and after their appointment to ensure follow-up and reduce missed appointments. “They help lupus patients connect with community services and overcoming barriers to access and care. The goal of this position is to improve overall disease management, which results in better health outcomes,” Ms. Costillo said.
Since its inception, the patient navigator program at WULC has shown a decrease in patient no-call no-shows and an increase in requests to reschedule as opposed to not showing up for their scheduled appointment, based on history.
Patients have reported fewer barriers to transportation and improvement in access to resources, support, and disease education. “Our patients have also stated [that] meeting with the navigator during their appointments has helped them to feel heard, understood, and supported,” Ms. Costillo said.
Navigator Work Is Not Without Challenges
A total of 90% of patients with lupus are women, and women of color are two to three times more likely to develop lupus in their lifetime.
“Based on socioeconomic statistics, lupus patients are in a demographic that is commonly underserved, underfunded, and often overlooked. Finding appropriate local community resources for a patient who must choose between feeding her family or paying for transportation to multiple physician appointments is a common problem,” Ms. Costillo said.
Much of the assistance that became available during the COVID pandemic is starting to disappear. “With the rising costs of daily living, we are having to find creative and alternative ways to break down barriers and find support to fill those gaps,” she continued.
Getting insurance coverage of patients is another challenge. Many patients with lupus will be prescribed a treatment that insurance refuses to cover even after the physician disputes it.
Additionally, many patients with lupus are unable to work to support their family. A majority who apply for Social Security Disability Insurance are denied on their first and second attempts, “requiring multiple hearings and pages of documentation from their physicians,” Ms. Costillo said.
Students Serve as Navigators
One inner-city program is seeking to increase access to healthcare services to patients with lupus and lupus nephritis in underserved communities. In 2021, SUNY Downstate Health Sciences University in New York City, in partnership with the Brooklyn Free Clinic and Brooklyn Health Disparities Center, launched a program to teach navigator skills to second-year medical students.
The students assist patients at the Arthritis Clinic at University Hospital at Downstate. “Many of our patients have either low medical literacy or difficulty with English. Many of them are immigrants,” said Ellen M. Ginzler, MD, MPH, SUNY Downstate’s professor emerita and former vice-chair for research and rheumatology division chief.
Dr. Ginzler sought out navigator candidates who showed a strong interest in working with underserved patients with complicated, severe disease who struggled with keeping appointments or adhering to medication regimens. The program also gave preference to students fluent in other languages such as Spanish.
All these efforts have generated improvements in care.
Assessing the program’s effectiveness in a cross-sectional study, Dr. Ginzler and colleagues reported that 94% of navigators were able to schedule appointments and 87% assisted with prescriptions. Navigators also had high success rates in answering medical questions, getting in touch with a patient’s doctor, and reminding patients of medical appointments.
Medical student Jeremy Wilson, a coauthor of the study, served as a navigator for a woman with lupus and scleroderma for many years, along with other comorbidities.
Mr. Wilson went above and beyond for this patient, helping to secure social services supports that included accompanying her to clinic visits and serving as her advocate. “She found an enormous difference in how she was treated when she went to these clinics because the doctors in those clinics took her much more seriously,” Dr. Ginzler said. Mr. Wilson ran interference to secure clinic appointments and worked with the patient’s rheumatology fellow in the clinic to get approval for medications.
Mr. Wilson and the patient formed a great bond. “It not only helped the patient, but it helped Jeremy tremendously in terms of how he felt about his medical career,” Dr. Ginzler said.
The program has since expanded to include patients with other rheumatic diseases, such as rheumatoid arthritis and psoriatic arthritis, and also offers navigator services in dermatology.
A total of 21 students to date have completed the second year of the program. “We’ve just selected eight more,” Dr. Ginzler said. Some of the students continue to do the program in their third or even fourth year as they’re applying for residencies.
A student-run, unpublished survey of nine students in the SUNY program found that all nine reported high confidence in identifying social factors that impact patient health and well-being, compared with four who reported high confidence prior to starting the program. “Additionally, students reported increased confidence in providing comprehensive care in rheumatology and dermatology, and interdisciplinary collaboration,” study author Alejandra K. Moncayo, MPH, and colleagues wrote.
When Navigators Go Virtual
Remission Medical offers its navigator service through its own standalone virtual clinic.
Pain associated with rheumatologic conditions increases the urgency to see a doctor. The goal of the virtual RemissionNavigator program is to meet rheumatology patients where they live, to bridge care gaps and reduce wait times, said Mr. Wehman.
RemissionNavigator accomplishes this through video visits and unlimited texting to its network of board-certified rheumatologists or rheumatology-focused advanced practice providers. Experts can answer questions about why labs are ordered, why a patient may have received a certain diagnosis, or provide detailed explanations of a rheumatic condition.
“There are instances where improvement for the patient means waiting a couple days for us versus 45 days for their brick-and-mortar choice,” Mr. Wehman said.
The program currently has 36 subscribers to Remission’s services, which include navigation. “We have 15 providers in a blend of employed and contracted relationships with Remission,” Mr. Wehman said.
Even in its infancy, the navigator program has produced some success stories. “We had a patient tell us that thanks to us, he was seen faster, found relief immediately through our diagnosis and prescription of methotrexate, felt better at work, lost weight, and was happier in general,” Mr. Wehman said.
Another patient was making monthly, 90-minute trips to Richmond for infusion services. Through the virtual program’s assistance, she is now receiving care from home and can get her monthly infusions at a local clinic.
Ultimately, the goal is to help rheumatology move into an era of value-based care where the transition from fee-for-service to per patient will enable optimized care models and better accessibility, Mr. Wehman said. “It will not happen overnight, but every day we work toward this future.”
VA Targets Rheumatology Care
The Department of Veterans Affairs (VA) has also explored the use of navigator services in rheumatology, including virtual services.
VA uses an integrated, interdisciplinary model that manages each veteran’s individual healthcare needs through a coordinated effort among providers, nurses, social workers, pharmacists, and other health professionals, according to VA press secretary Terrence Hayes.
Care coordination may include supporting scheduling appointments, managing chronic conditions, and coordinating care across different medical departments. “This coordination is particularly important in managing complex rheumatologic conditions, where multiple providers may be involved,” Mr. Hayes said.
Additionally, VA has launched a national telerheumatology initiative to improve access to rheumatology providers in rural areas. The initiative will assist veterans in understanding the telehealth system, navigating appointments, and ensuring they have the necessary technology for virtual consultations.
“It will also facilitate communication between rheumatologists, primary care providers, and other specialists, ensuring that all team members are aligned in their approach to the veteran’s care,” Mr. Hayes said.
Who Will Take Advantage of New Codes?
Currently, Remission Medical operates on a cash-pay model, but the company intends to transition to insurance-based coverage in 2025.
Remission Medical also partners directly with preexisting healthcare systems and clinics such as Sentara Health and OrthoVirginia, where a PIN program, powered by Remission Medical’s virtual rheumatology network, may be explored as well.
The company offers its partners synchronous virtual visits and e-consults. It’s likely that these larger organizations will explore coverage for navigator services for Medicare and private insurance. “We can be there to support them as they decide to implement this,” Mr. Wehman said.
Taking advantage of CMS’s navigator PIN codes is an eventual goal. Remission Medical has not submitted the codes yet, “but we do intend to as we continue to grow our membership count,” Mr. Wehman said. “We hope to provide coverage for most of the US and submit the codes to reimbursement by early to mid-2025.”
In terms of reimbursement, the VA operates under a different payment model than Medicare or private insurance, focusing on providing integrated care within the VA system rather than reimbursing for specific services such as patient navigation.
While the SUNY clinic takes care of Medicare patients, it’s unlikely that the new CMS codes for navigators would apply to medical students. Students get paid a monthly stipend for doing navigator work. “There’s a policy about what students can get paid, and how many hours they can work,” Dr. Ginzler clarified.
The SUNY Downstate and Lupus Foundation navigator programs rely on grants to sustain their services. Aurinia Pharmaceuticals has funded both programs, and the SUNY program received an additional grant from Janssen to expand its offerings.
Because it’s grant funded, the navigator position at the Lupus Foundation does not bill patient insurance, Ms. Costillo explained.
Navigator Work Requires Training
Before they start working with patients, navigators often go through a vetting or training process. At Remission Medical, a clinical leadership team does a synchronous interview, background check, and CV review of its potential navigators.
Even before she became a navigator, Ms. Costillo had a strong baseline education in this work. She has a bachelor’s degree in social work and 15 years of experience in social services working with disabled, vulnerable, and underserved populations. Some of her fellow navigators at the Lupus Foundation of America also have degrees in social work.
Ms. Costillo underwent training with the Patient-Centered Education & Research Institute to become a certified professional patient navigator. Her name is on the national registry. The curriculum covered various aspects of medical care such as patient and care team interactions and communications, health and clinical knowledge, patient care coordination and resources, and using evidence-based approaches.
“For our lupus patients, it is essential that navigators understand the disease and the impact on patients and families, treatments available and those in the pipelines, and also the ins and outs of various insurance options,” Ms. Costillo said.
Mr. Wehman, Dr. Williams, and Ms. Costillo reported no disclosures. Dr. Ginzler has been a consultant for Aurinia Pharmaceuticals.
A version of this article first appeared on Medscape.com.
When a large rheumatology clinic in Richmond, Virginia, heard that Medicare would be reimbursing patient navigators, they decided to launch their own virtual navigator program.
“We read about it and felt like it was the perfect representation of what we were already trying to do,” said Blake Wehman, founder and CEO of Remission Medical, which offers virtual diagnosis and longitudinal care in rheumatology.
Mr. Wehman has plans to start submitting for these principal illness navigation (PIN) codes in 2025.
The Centers for Medicare & Medicaid Services (CMS) in 2024 began paying navigators who assist Medicare patients with high-risk conditions, which could include rheumatologic diseases. “The codes are not limited to a specific set of diagnoses; rather, the definition of a serious, high-risk condition is dependent on clinical judgment,” the agency clarified.
CMS established this provision in the CY 2024 Physician Fee Schedule final rule.
Reimbursing patient navigators is long overdue, noted Edith Williams, PhD, MS, director of the Center for Community Health and Prevention and founding director of the Office of Health Equity Research at the University of Rochester in New York. “It’s something our patients need. It’s something that the science is telling us can impact outcomes as an adjunct to clinical care,” she said.
Dr. Williams said the new CMS codes “got our departments talking about what this policy is and how it would translate into patient care.”
The codes apply when navigators are assigned to support patients with high-risk conditions who need assistance connecting with clinical and other resources, including any unmet social determinants of health needs, or in diagnosis or treatment of their medical problems.
“Having a navigator by their side to help get through all the clinical and administrative challenges gives people an advocate and a partner who is with them and their families every step of the way to help make the journey easier,” said a CMS spokesperson.
Not all navigator programs may qualify for the new codes. Some are supported by grants and don’t bill patient insurance. However, they all share a common goal: to guide patients through the healthcare continuum and assist with appointments and medication adherence.
Identifying ‘Root Causes’ of Barriers
Navigators represent a wide variety of backgrounds, ranging from healthcare professionals to students or even patients themselves. They generally don’t provide medical advice. “However, we are responsible for making sure our patients and their families are educated and aware, then assist with guidance on their path,” said Katie Costillo, BSW, CPPN, patient navigator and program manager with the Lupus Foundation of America, Heartland Region.
“Training and experience in engaging and building rapport is essential to assisting patients overcome obstacles that limit their access to healthcare,” she said. Narrowing down with patients the root causes of their barriers and then identifying appropriate and available community resources is key.
Studies have demonstrated the effectiveness of adding a navigator to a rheumatology patient’s care plan. In one study, a group of Boston researchers determined that navigators played a useful role in reducing adherence barriers to oral disease-modifying antirheumatic drugs. The navigators uncovered several concerns among 107 rheumatology patients, including fear of adverse events and medication effectiveness.
They also helped to facilitate patient-physician communication, developed strategies to improve medication adherence, and provided medication and diagnosis education. Patients reported satisfaction with the navigator experience.
A study Dr. Williams coauthored that examined behavioral interventions to support African American women with systemic lupus erythematosus found that patient navigator participants had superior coping scores, compared with those engaged in peer-to-peer methodology and patient support groups.
“We had a lot of success with the mentorship program, too,” Dr. Williams said. Navigator services, however, offer more one-on-one attention, “and it’s more tailored to what the person needs rather than the set curriculum that the mentors delivered to their mentees.”
Supporting Patients With Lupus
Ideally, navigators should be able to relate to patients and know what they’re going through, Dr. Williams said. This is someone whom the patient can trust and depend on. “That’s where the benefit of having someone who is also a patient lies because they’re ultimately relatable to other patients. But different institutions have taken different approaches to this.”
Some programs focus on specific rheumatologic conditions. The Lupus Foundation of America, for example, established patient navigator programs to assist patients with lupus in four markets across the country.
The Heartland patient navigator program is available for all patients with lupus within its region, which includes Kansas, Missouri, and central and southern Illinois. As a navigator, Ms. Costillo has been assisting patients since 2022. In 2023, she began meeting with patients at the Washington University Lupus Clinic (WULC) in St. Louis, Missouri.
Navigators work directly with patients before and after their appointment to ensure follow-up and reduce missed appointments. “They help lupus patients connect with community services and overcoming barriers to access and care. The goal of this position is to improve overall disease management, which results in better health outcomes,” Ms. Costillo said.
Since its inception, the patient navigator program at WULC has shown a decrease in patient no-call no-shows and an increase in requests to reschedule as opposed to not showing up for their scheduled appointment, based on history.
Patients have reported fewer barriers to transportation and improvement in access to resources, support, and disease education. “Our patients have also stated [that] meeting with the navigator during their appointments has helped them to feel heard, understood, and supported,” Ms. Costillo said.
Navigator Work Is Not Without Challenges
A total of 90% of patients with lupus are women, and women of color are two to three times more likely to develop lupus in their lifetime.
“Based on socioeconomic statistics, lupus patients are in a demographic that is commonly underserved, underfunded, and often overlooked. Finding appropriate local community resources for a patient who must choose between feeding her family or paying for transportation to multiple physician appointments is a common problem,” Ms. Costillo said.
Much of the assistance that became available during the COVID pandemic is starting to disappear. “With the rising costs of daily living, we are having to find creative and alternative ways to break down barriers and find support to fill those gaps,” she continued.
Getting insurance coverage of patients is another challenge. Many patients with lupus will be prescribed a treatment that insurance refuses to cover even after the physician disputes it.
Additionally, many patients with lupus are unable to work to support their family. A majority who apply for Social Security Disability Insurance are denied on their first and second attempts, “requiring multiple hearings and pages of documentation from their physicians,” Ms. Costillo said.
Students Serve as Navigators
One inner-city program is seeking to increase access to healthcare services to patients with lupus and lupus nephritis in underserved communities. In 2021, SUNY Downstate Health Sciences University in New York City, in partnership with the Brooklyn Free Clinic and Brooklyn Health Disparities Center, launched a program to teach navigator skills to second-year medical students.
The students assist patients at the Arthritis Clinic at University Hospital at Downstate. “Many of our patients have either low medical literacy or difficulty with English. Many of them are immigrants,” said Ellen M. Ginzler, MD, MPH, SUNY Downstate’s professor emerita and former vice-chair for research and rheumatology division chief.
Dr. Ginzler sought out navigator candidates who showed a strong interest in working with underserved patients with complicated, severe disease who struggled with keeping appointments or adhering to medication regimens. The program also gave preference to students fluent in other languages such as Spanish.
All these efforts have generated improvements in care.
Assessing the program’s effectiveness in a cross-sectional study, Dr. Ginzler and colleagues reported that 94% of navigators were able to schedule appointments and 87% assisted with prescriptions. Navigators also had high success rates in answering medical questions, getting in touch with a patient’s doctor, and reminding patients of medical appointments.
Medical student Jeremy Wilson, a coauthor of the study, served as a navigator for a woman with lupus and scleroderma for many years, along with other comorbidities.
Mr. Wilson went above and beyond for this patient, helping to secure social services supports that included accompanying her to clinic visits and serving as her advocate. “She found an enormous difference in how she was treated when she went to these clinics because the doctors in those clinics took her much more seriously,” Dr. Ginzler said. Mr. Wilson ran interference to secure clinic appointments and worked with the patient’s rheumatology fellow in the clinic to get approval for medications.
Mr. Wilson and the patient formed a great bond. “It not only helped the patient, but it helped Jeremy tremendously in terms of how he felt about his medical career,” Dr. Ginzler said.
The program has since expanded to include patients with other rheumatic diseases, such as rheumatoid arthritis and psoriatic arthritis, and also offers navigator services in dermatology.
A total of 21 students to date have completed the second year of the program. “We’ve just selected eight more,” Dr. Ginzler said. Some of the students continue to do the program in their third or even fourth year as they’re applying for residencies.
A student-run, unpublished survey of nine students in the SUNY program found that all nine reported high confidence in identifying social factors that impact patient health and well-being, compared with four who reported high confidence prior to starting the program. “Additionally, students reported increased confidence in providing comprehensive care in rheumatology and dermatology, and interdisciplinary collaboration,” study author Alejandra K. Moncayo, MPH, and colleagues wrote.
When Navigators Go Virtual
Remission Medical offers its navigator service through its own standalone virtual clinic.
Pain associated with rheumatologic conditions increases the urgency to see a doctor. The goal of the virtual RemissionNavigator program is to meet rheumatology patients where they live, to bridge care gaps and reduce wait times, said Mr. Wehman.
RemissionNavigator accomplishes this through video visits and unlimited texting to its network of board-certified rheumatologists or rheumatology-focused advanced practice providers. Experts can answer questions about why labs are ordered, why a patient may have received a certain diagnosis, or provide detailed explanations of a rheumatic condition.
“There are instances where improvement for the patient means waiting a couple days for us versus 45 days for their brick-and-mortar choice,” Mr. Wehman said.
The program currently has 36 subscribers to Remission’s services, which include navigation. “We have 15 providers in a blend of employed and contracted relationships with Remission,” Mr. Wehman said.
Even in its infancy, the navigator program has produced some success stories. “We had a patient tell us that thanks to us, he was seen faster, found relief immediately through our diagnosis and prescription of methotrexate, felt better at work, lost weight, and was happier in general,” Mr. Wehman said.
Another patient was making monthly, 90-minute trips to Richmond for infusion services. Through the virtual program’s assistance, she is now receiving care from home and can get her monthly infusions at a local clinic.
Ultimately, the goal is to help rheumatology move into an era of value-based care where the transition from fee-for-service to per patient will enable optimized care models and better accessibility, Mr. Wehman said. “It will not happen overnight, but every day we work toward this future.”
VA Targets Rheumatology Care
The Department of Veterans Affairs (VA) has also explored the use of navigator services in rheumatology, including virtual services.
VA uses an integrated, interdisciplinary model that manages each veteran’s individual healthcare needs through a coordinated effort among providers, nurses, social workers, pharmacists, and other health professionals, according to VA press secretary Terrence Hayes.
Care coordination may include supporting scheduling appointments, managing chronic conditions, and coordinating care across different medical departments. “This coordination is particularly important in managing complex rheumatologic conditions, where multiple providers may be involved,” Mr. Hayes said.
Additionally, VA has launched a national telerheumatology initiative to improve access to rheumatology providers in rural areas. The initiative will assist veterans in understanding the telehealth system, navigating appointments, and ensuring they have the necessary technology for virtual consultations.
“It will also facilitate communication between rheumatologists, primary care providers, and other specialists, ensuring that all team members are aligned in their approach to the veteran’s care,” Mr. Hayes said.
Who Will Take Advantage of New Codes?
Currently, Remission Medical operates on a cash-pay model, but the company intends to transition to insurance-based coverage in 2025.
Remission Medical also partners directly with preexisting healthcare systems and clinics such as Sentara Health and OrthoVirginia, where a PIN program, powered by Remission Medical’s virtual rheumatology network, may be explored as well.
The company offers its partners synchronous virtual visits and e-consults. It’s likely that these larger organizations will explore coverage for navigator services for Medicare and private insurance. “We can be there to support them as they decide to implement this,” Mr. Wehman said.
Taking advantage of CMS’s navigator PIN codes is an eventual goal. Remission Medical has not submitted the codes yet, “but we do intend to as we continue to grow our membership count,” Mr. Wehman said. “We hope to provide coverage for most of the US and submit the codes to reimbursement by early to mid-2025.”
In terms of reimbursement, the VA operates under a different payment model than Medicare or private insurance, focusing on providing integrated care within the VA system rather than reimbursing for specific services such as patient navigation.
While the SUNY clinic takes care of Medicare patients, it’s unlikely that the new CMS codes for navigators would apply to medical students. Students get paid a monthly stipend for doing navigator work. “There’s a policy about what students can get paid, and how many hours they can work,” Dr. Ginzler clarified.
The SUNY Downstate and Lupus Foundation navigator programs rely on grants to sustain their services. Aurinia Pharmaceuticals has funded both programs, and the SUNY program received an additional grant from Janssen to expand its offerings.
Because it’s grant funded, the navigator position at the Lupus Foundation does not bill patient insurance, Ms. Costillo explained.
Navigator Work Requires Training
Before they start working with patients, navigators often go through a vetting or training process. At Remission Medical, a clinical leadership team does a synchronous interview, background check, and CV review of its potential navigators.
Even before she became a navigator, Ms. Costillo had a strong baseline education in this work. She has a bachelor’s degree in social work and 15 years of experience in social services working with disabled, vulnerable, and underserved populations. Some of her fellow navigators at the Lupus Foundation of America also have degrees in social work.
Ms. Costillo underwent training with the Patient-Centered Education & Research Institute to become a certified professional patient navigator. Her name is on the national registry. The curriculum covered various aspects of medical care such as patient and care team interactions and communications, health and clinical knowledge, patient care coordination and resources, and using evidence-based approaches.
“For our lupus patients, it is essential that navigators understand the disease and the impact on patients and families, treatments available and those in the pipelines, and also the ins and outs of various insurance options,” Ms. Costillo said.
Mr. Wehman, Dr. Williams, and Ms. Costillo reported no disclosures. Dr. Ginzler has been a consultant for Aurinia Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Trial Looks at Early Use of Mycophenolate to Reduce Flares, Nephritis
Early use of mycophenolate mofetil (MMF), a drug used to dampen the immune system in organ transplant recipients, may reduce the risk for severe flares in patients with newly diagnosed systemic lupus erythematosus (SLE), according to results from a randomized, open-label, observer-blinded clinical trial.
In interviews, two SLE specialists who were not involved with the study said the research is preliminary but promising. However, another specialist criticized the paper’s reliance on unusual doses of prednisone and MMF, saying it “puts people on a treatment regimen that nobody ever uses.”
The Lupus Foundation of America estimates that about 16,000 people in the United States are diagnosed with lupus each year. “Our current treatment paradigm is to go pretty slowly and start treatment for new-onset, mild SLE with glucocorticoids, if necessary, and hydroxychloroquine,” said Karen H. Costenbader, MD, MPH, of Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts.
Stronger immunosuppressive agents may be added as patients progress, she said.
Off-label use of MMF, which is approved by the Food and Drug Administration only for patients with certain organ transplants, may be appropriate in some cases, she said. “There is a big push to start immunosuppressives earlier, but we currently would reserve mycophenolate for those with severe manifestations — lupus nephritis; vasculitis; or lung, brain, or heart inflammation.”
In the trial, adult patients who received oral prednisone (starting at 0.5 mg/kg per day) and hydroxychloroquine sulfate (5 mg/kg per day) plus MMF (500 mg twice daily) for 96 weeks were less likely to develop severe flares than those who took the regimen without MMF (relative risk [RR], 0.39; 95% CI, 0.17-0.87; P = .01). Severe flares occurred in 10.8% of the MMF group (7 of 65 patients) and in 27.7% of the control group (18 of 65), Yijun You, MD, of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and colleagues reported in JAMA Network Open.
Patients in the MMF group also had 89% lower risk for lupus nephritis than those in the control group (RR, 0.11; 95% CI, 0.01-0.85; P = .008), with kidney involvement occurring in 1.5% (1 of 65) vs 13.8% (9 of 65).
During 2018-2021, researchers recruited 130 patients in China aged 18-65 years with newly diagnosed SLE, a high titer of anti–double-stranded DNA (dsDNA) antibodies, and no major organ involvement (mean age, 34.5 years; 86.2% women). Patients’ initial 0.5–mg/kg per day prednisone dose was maintained for 4 weeks, then tapered by 5.0 mg every 2 weeks, and when the dose had been reduced to 20.0 mg/day, it was tapered by 5 mg every month and then gradually to 0.1-0.2 mg/kg per day. If patients had severe flares, they stopped taking MMF. (The study authors did not respond to requests for comment on the study.)
‘A Treatment Regimen That Nobody Ever Uses’
While Dr. Costenbader called the study “very interesting” and said “every person diagnosing or taking care of patients with lupus should be familiar” with it, she noted that the prednisone doses were high. “I am wondering why they used quite so much glucocorticoid for everyone. This may have masked some of the MMF effect and biased toward the null. They also used a low dose of MMF and did not ramp it up as we would normally to a full dose. That being said, it is remarkable that it was well-tolerated and resulted in better outcomes over the period of the trial.”
Daniel J. Wallace, MD, of Cedars-Sinai Medical Center, Los Angeles, California, and the University of California, Los Angeles, also highlighted the high doses of prednisone and low doses of MMF. “It’s a useless paper that puts people on a treatment regimen that nobody ever uses,” he said.
The rates of mild to moderate flares were similar between the control and intervention groups (38.5% vs 36.9%, respectively; RR, 0.96; P = .90). This finding is surprising, said Judith A. James, MD, PhD, executive vice president, chief medical officer, and head of the rheumatology clinic and Arthritis and Clinical Immunology Research Program at the Oklahoma Medical Research Foundation in Oklahoma City and also the Associate Vice Provost of Clinical & Translational Science, professor of medicine, and George Lynn Cross Research Professor at the University of Oklahoma Health Sciences Center in Oklahoma City. “It may be that mild flares have a different mechanism or are caused by noninflammatory endotypes that don’t respond to MMF.”
Dr. Costenbader noted that a risk-benefit analysis will need to be done to take the risks of MMF into account. “However, every time that a person flares or is not in lupus low-disease activity state, potentially permanent organ damage is done and the patient suffers,” she said. “Preventing lupus nephritis de novo was also seen — nine cases potentially prevented — and that is also really interesting. It would be amazing if we could completely avoid that life-threatening complication.”
MMF can cause miscarriage and boost the risk for birth defects, and the manufacturer says it can lower the effectiveness of birth control pills. It can also boost the risk for some cancers such as lymphoma and increase the risk for infections.
Surprisingly, the number of adverse events in the control and intervention groups were similar (35.4% vs 46.2%, respectively; RR, 1.30; 95% CI, 0.86-1.99; P = .20). They included infection (30.8% vs 33.8%, respectively; P = .70) and gastrointestinal tract events (16.9% for both; P > .99).
“There were overall pretty similar rates of side effects, but maybe this was because MMF dose was pretty low in the treated group, or the glucocorticoid dose was not so low in both groups,” Dr. Costenbader said. She also noted that “the risk of malignancy with MMF is longer term than this study. It may not show up for 5-10 or even more years, but we know it exists. Infections are also increased with MMF — some of which can be avoided with vaccines for COVID, pneumonia, influenza, shingles, etc. MMF also causes gastrointestinal intolerance, and people often are not able to take it because of nausea, vomiting, diarrhea, and elevated liver function tests.”
Dr. James said the infection rates “may be due to the higher doses of steroids patients in both groups are on for several months at the beginning of the study.”
A total of 12 patients in the MMF group discontinued the intervention for various reasons, and 6 were lost to follow-up. In the control group, 20 discontinued the intervention and two were lost to follow-up. However, all 130 patients in the trial were included in the primary and secondary outcome analyses.
Should clinicians consider prescribing MMF to patients with new-onset SLE? “We usually wait until later when there are indications of more severe disease, but here they started it from the time of diagnosis if the patient was anti-dsDNA positive. Given insurance restrictions in this country, we would be unlikely to be able to do that for many patients,” Dr. Costenbader said. “They likely also overtreated a lot of patients who didn’t need it. Due to our lack of more specific biomarkers and precision medicine for lupus, we do currently undertreat a lot of patients, as this study highlights, as well as overtreat others.”
How Much Might Cost Factor Into Treatment Decisions?
The study did not examine cost. Prednisone and hydroxychloroquine sulfate are inexpensive, but Dr. James said MMF can cost about $450 a month at the study dosage. However, “the average hospitalization without an ICU [intensive care unit] visit for an SLE patient is about $15,000-$20,000. If you can avoid one hospitalization, you can pay for nearly 4 years of MMF. More importantly, from a financial perspective, if you can convert a severe lupus patient to a mild/moderate lupus patient, then the annual costs of lupus decrease nearly by half, from about $52,000 per year to $25,000 per year.”
The study authors noted various limitations such as the small number of subjects, the need for a longer trial “to determine the advantages and disadvantages of early application of MMF,” and the fact that all subjects were Asian. The authors also called for confirmation via a double-blind, placebo-controlled study.
The study was funded by grants to the authors by the National Natural Science Foundation of China, Shanghai Rising-Star Program, Natural Science Foundation of Shanghai, Five-Year National Key R&D Program, and Ruijin–Zhongmei Huadong Lupus Funding. The authors had no disclosures. Dr. Costenbader disclosed consulting/research collaboration relationships with AstraZeneca, Amgen, Biogen, Bristol-Myers Squibb, GSK, Merck, Gilead, and Cabaletta. Dr. James and Dr. Wallace had no disclosures.
A version of this article first appeared on Medscape.com.
Early use of mycophenolate mofetil (MMF), a drug used to dampen the immune system in organ transplant recipients, may reduce the risk for severe flares in patients with newly diagnosed systemic lupus erythematosus (SLE), according to results from a randomized, open-label, observer-blinded clinical trial.
In interviews, two SLE specialists who were not involved with the study said the research is preliminary but promising. However, another specialist criticized the paper’s reliance on unusual doses of prednisone and MMF, saying it “puts people on a treatment regimen that nobody ever uses.”
The Lupus Foundation of America estimates that about 16,000 people in the United States are diagnosed with lupus each year. “Our current treatment paradigm is to go pretty slowly and start treatment for new-onset, mild SLE with glucocorticoids, if necessary, and hydroxychloroquine,” said Karen H. Costenbader, MD, MPH, of Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts.
Stronger immunosuppressive agents may be added as patients progress, she said.
Off-label use of MMF, which is approved by the Food and Drug Administration only for patients with certain organ transplants, may be appropriate in some cases, she said. “There is a big push to start immunosuppressives earlier, but we currently would reserve mycophenolate for those with severe manifestations — lupus nephritis; vasculitis; or lung, brain, or heart inflammation.”
In the trial, adult patients who received oral prednisone (starting at 0.5 mg/kg per day) and hydroxychloroquine sulfate (5 mg/kg per day) plus MMF (500 mg twice daily) for 96 weeks were less likely to develop severe flares than those who took the regimen without MMF (relative risk [RR], 0.39; 95% CI, 0.17-0.87; P = .01). Severe flares occurred in 10.8% of the MMF group (7 of 65 patients) and in 27.7% of the control group (18 of 65), Yijun You, MD, of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and colleagues reported in JAMA Network Open.
Patients in the MMF group also had 89% lower risk for lupus nephritis than those in the control group (RR, 0.11; 95% CI, 0.01-0.85; P = .008), with kidney involvement occurring in 1.5% (1 of 65) vs 13.8% (9 of 65).
During 2018-2021, researchers recruited 130 patients in China aged 18-65 years with newly diagnosed SLE, a high titer of anti–double-stranded DNA (dsDNA) antibodies, and no major organ involvement (mean age, 34.5 years; 86.2% women). Patients’ initial 0.5–mg/kg per day prednisone dose was maintained for 4 weeks, then tapered by 5.0 mg every 2 weeks, and when the dose had been reduced to 20.0 mg/day, it was tapered by 5 mg every month and then gradually to 0.1-0.2 mg/kg per day. If patients had severe flares, they stopped taking MMF. (The study authors did not respond to requests for comment on the study.)
‘A Treatment Regimen That Nobody Ever Uses’
While Dr. Costenbader called the study “very interesting” and said “every person diagnosing or taking care of patients with lupus should be familiar” with it, she noted that the prednisone doses were high. “I am wondering why they used quite so much glucocorticoid for everyone. This may have masked some of the MMF effect and biased toward the null. They also used a low dose of MMF and did not ramp it up as we would normally to a full dose. That being said, it is remarkable that it was well-tolerated and resulted in better outcomes over the period of the trial.”
Daniel J. Wallace, MD, of Cedars-Sinai Medical Center, Los Angeles, California, and the University of California, Los Angeles, also highlighted the high doses of prednisone and low doses of MMF. “It’s a useless paper that puts people on a treatment regimen that nobody ever uses,” he said.
The rates of mild to moderate flares were similar between the control and intervention groups (38.5% vs 36.9%, respectively; RR, 0.96; P = .90). This finding is surprising, said Judith A. James, MD, PhD, executive vice president, chief medical officer, and head of the rheumatology clinic and Arthritis and Clinical Immunology Research Program at the Oklahoma Medical Research Foundation in Oklahoma City and also the Associate Vice Provost of Clinical & Translational Science, professor of medicine, and George Lynn Cross Research Professor at the University of Oklahoma Health Sciences Center in Oklahoma City. “It may be that mild flares have a different mechanism or are caused by noninflammatory endotypes that don’t respond to MMF.”
Dr. Costenbader noted that a risk-benefit analysis will need to be done to take the risks of MMF into account. “However, every time that a person flares or is not in lupus low-disease activity state, potentially permanent organ damage is done and the patient suffers,” she said. “Preventing lupus nephritis de novo was also seen — nine cases potentially prevented — and that is also really interesting. It would be amazing if we could completely avoid that life-threatening complication.”
MMF can cause miscarriage and boost the risk for birth defects, and the manufacturer says it can lower the effectiveness of birth control pills. It can also boost the risk for some cancers such as lymphoma and increase the risk for infections.
Surprisingly, the number of adverse events in the control and intervention groups were similar (35.4% vs 46.2%, respectively; RR, 1.30; 95% CI, 0.86-1.99; P = .20). They included infection (30.8% vs 33.8%, respectively; P = .70) and gastrointestinal tract events (16.9% for both; P > .99).
“There were overall pretty similar rates of side effects, but maybe this was because MMF dose was pretty low in the treated group, or the glucocorticoid dose was not so low in both groups,” Dr. Costenbader said. She also noted that “the risk of malignancy with MMF is longer term than this study. It may not show up for 5-10 or even more years, but we know it exists. Infections are also increased with MMF — some of which can be avoided with vaccines for COVID, pneumonia, influenza, shingles, etc. MMF also causes gastrointestinal intolerance, and people often are not able to take it because of nausea, vomiting, diarrhea, and elevated liver function tests.”
Dr. James said the infection rates “may be due to the higher doses of steroids patients in both groups are on for several months at the beginning of the study.”
A total of 12 patients in the MMF group discontinued the intervention for various reasons, and 6 were lost to follow-up. In the control group, 20 discontinued the intervention and two were lost to follow-up. However, all 130 patients in the trial were included in the primary and secondary outcome analyses.
Should clinicians consider prescribing MMF to patients with new-onset SLE? “We usually wait until later when there are indications of more severe disease, but here they started it from the time of diagnosis if the patient was anti-dsDNA positive. Given insurance restrictions in this country, we would be unlikely to be able to do that for many patients,” Dr. Costenbader said. “They likely also overtreated a lot of patients who didn’t need it. Due to our lack of more specific biomarkers and precision medicine for lupus, we do currently undertreat a lot of patients, as this study highlights, as well as overtreat others.”
How Much Might Cost Factor Into Treatment Decisions?
The study did not examine cost. Prednisone and hydroxychloroquine sulfate are inexpensive, but Dr. James said MMF can cost about $450 a month at the study dosage. However, “the average hospitalization without an ICU [intensive care unit] visit for an SLE patient is about $15,000-$20,000. If you can avoid one hospitalization, you can pay for nearly 4 years of MMF. More importantly, from a financial perspective, if you can convert a severe lupus patient to a mild/moderate lupus patient, then the annual costs of lupus decrease nearly by half, from about $52,000 per year to $25,000 per year.”
The study authors noted various limitations such as the small number of subjects, the need for a longer trial “to determine the advantages and disadvantages of early application of MMF,” and the fact that all subjects were Asian. The authors also called for confirmation via a double-blind, placebo-controlled study.
The study was funded by grants to the authors by the National Natural Science Foundation of China, Shanghai Rising-Star Program, Natural Science Foundation of Shanghai, Five-Year National Key R&D Program, and Ruijin–Zhongmei Huadong Lupus Funding. The authors had no disclosures. Dr. Costenbader disclosed consulting/research collaboration relationships with AstraZeneca, Amgen, Biogen, Bristol-Myers Squibb, GSK, Merck, Gilead, and Cabaletta. Dr. James and Dr. Wallace had no disclosures.
A version of this article first appeared on Medscape.com.
Early use of mycophenolate mofetil (MMF), a drug used to dampen the immune system in organ transplant recipients, may reduce the risk for severe flares in patients with newly diagnosed systemic lupus erythematosus (SLE), according to results from a randomized, open-label, observer-blinded clinical trial.
In interviews, two SLE specialists who were not involved with the study said the research is preliminary but promising. However, another specialist criticized the paper’s reliance on unusual doses of prednisone and MMF, saying it “puts people on a treatment regimen that nobody ever uses.”
The Lupus Foundation of America estimates that about 16,000 people in the United States are diagnosed with lupus each year. “Our current treatment paradigm is to go pretty slowly and start treatment for new-onset, mild SLE with glucocorticoids, if necessary, and hydroxychloroquine,” said Karen H. Costenbader, MD, MPH, of Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts.
Stronger immunosuppressive agents may be added as patients progress, she said.
Off-label use of MMF, which is approved by the Food and Drug Administration only for patients with certain organ transplants, may be appropriate in some cases, she said. “There is a big push to start immunosuppressives earlier, but we currently would reserve mycophenolate for those with severe manifestations — lupus nephritis; vasculitis; or lung, brain, or heart inflammation.”
In the trial, adult patients who received oral prednisone (starting at 0.5 mg/kg per day) and hydroxychloroquine sulfate (5 mg/kg per day) plus MMF (500 mg twice daily) for 96 weeks were less likely to develop severe flares than those who took the regimen without MMF (relative risk [RR], 0.39; 95% CI, 0.17-0.87; P = .01). Severe flares occurred in 10.8% of the MMF group (7 of 65 patients) and in 27.7% of the control group (18 of 65), Yijun You, MD, of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and colleagues reported in JAMA Network Open.
Patients in the MMF group also had 89% lower risk for lupus nephritis than those in the control group (RR, 0.11; 95% CI, 0.01-0.85; P = .008), with kidney involvement occurring in 1.5% (1 of 65) vs 13.8% (9 of 65).
During 2018-2021, researchers recruited 130 patients in China aged 18-65 years with newly diagnosed SLE, a high titer of anti–double-stranded DNA (dsDNA) antibodies, and no major organ involvement (mean age, 34.5 years; 86.2% women). Patients’ initial 0.5–mg/kg per day prednisone dose was maintained for 4 weeks, then tapered by 5.0 mg every 2 weeks, and when the dose had been reduced to 20.0 mg/day, it was tapered by 5 mg every month and then gradually to 0.1-0.2 mg/kg per day. If patients had severe flares, they stopped taking MMF. (The study authors did not respond to requests for comment on the study.)
‘A Treatment Regimen That Nobody Ever Uses’
While Dr. Costenbader called the study “very interesting” and said “every person diagnosing or taking care of patients with lupus should be familiar” with it, she noted that the prednisone doses were high. “I am wondering why they used quite so much glucocorticoid for everyone. This may have masked some of the MMF effect and biased toward the null. They also used a low dose of MMF and did not ramp it up as we would normally to a full dose. That being said, it is remarkable that it was well-tolerated and resulted in better outcomes over the period of the trial.”
Daniel J. Wallace, MD, of Cedars-Sinai Medical Center, Los Angeles, California, and the University of California, Los Angeles, also highlighted the high doses of prednisone and low doses of MMF. “It’s a useless paper that puts people on a treatment regimen that nobody ever uses,” he said.
The rates of mild to moderate flares were similar between the control and intervention groups (38.5% vs 36.9%, respectively; RR, 0.96; P = .90). This finding is surprising, said Judith A. James, MD, PhD, executive vice president, chief medical officer, and head of the rheumatology clinic and Arthritis and Clinical Immunology Research Program at the Oklahoma Medical Research Foundation in Oklahoma City and also the Associate Vice Provost of Clinical & Translational Science, professor of medicine, and George Lynn Cross Research Professor at the University of Oklahoma Health Sciences Center in Oklahoma City. “It may be that mild flares have a different mechanism or are caused by noninflammatory endotypes that don’t respond to MMF.”
Dr. Costenbader noted that a risk-benefit analysis will need to be done to take the risks of MMF into account. “However, every time that a person flares or is not in lupus low-disease activity state, potentially permanent organ damage is done and the patient suffers,” she said. “Preventing lupus nephritis de novo was also seen — nine cases potentially prevented — and that is also really interesting. It would be amazing if we could completely avoid that life-threatening complication.”
MMF can cause miscarriage and boost the risk for birth defects, and the manufacturer says it can lower the effectiveness of birth control pills. It can also boost the risk for some cancers such as lymphoma and increase the risk for infections.
Surprisingly, the number of adverse events in the control and intervention groups were similar (35.4% vs 46.2%, respectively; RR, 1.30; 95% CI, 0.86-1.99; P = .20). They included infection (30.8% vs 33.8%, respectively; P = .70) and gastrointestinal tract events (16.9% for both; P > .99).
“There were overall pretty similar rates of side effects, but maybe this was because MMF dose was pretty low in the treated group, or the glucocorticoid dose was not so low in both groups,” Dr. Costenbader said. She also noted that “the risk of malignancy with MMF is longer term than this study. It may not show up for 5-10 or even more years, but we know it exists. Infections are also increased with MMF — some of which can be avoided with vaccines for COVID, pneumonia, influenza, shingles, etc. MMF also causes gastrointestinal intolerance, and people often are not able to take it because of nausea, vomiting, diarrhea, and elevated liver function tests.”
Dr. James said the infection rates “may be due to the higher doses of steroids patients in both groups are on for several months at the beginning of the study.”
A total of 12 patients in the MMF group discontinued the intervention for various reasons, and 6 were lost to follow-up. In the control group, 20 discontinued the intervention and two were lost to follow-up. However, all 130 patients in the trial were included in the primary and secondary outcome analyses.
Should clinicians consider prescribing MMF to patients with new-onset SLE? “We usually wait until later when there are indications of more severe disease, but here they started it from the time of diagnosis if the patient was anti-dsDNA positive. Given insurance restrictions in this country, we would be unlikely to be able to do that for many patients,” Dr. Costenbader said. “They likely also overtreated a lot of patients who didn’t need it. Due to our lack of more specific biomarkers and precision medicine for lupus, we do currently undertreat a lot of patients, as this study highlights, as well as overtreat others.”
How Much Might Cost Factor Into Treatment Decisions?
The study did not examine cost. Prednisone and hydroxychloroquine sulfate are inexpensive, but Dr. James said MMF can cost about $450 a month at the study dosage. However, “the average hospitalization without an ICU [intensive care unit] visit for an SLE patient is about $15,000-$20,000. If you can avoid one hospitalization, you can pay for nearly 4 years of MMF. More importantly, from a financial perspective, if you can convert a severe lupus patient to a mild/moderate lupus patient, then the annual costs of lupus decrease nearly by half, from about $52,000 per year to $25,000 per year.”
The study authors noted various limitations such as the small number of subjects, the need for a longer trial “to determine the advantages and disadvantages of early application of MMF,” and the fact that all subjects were Asian. The authors also called for confirmation via a double-blind, placebo-controlled study.
The study was funded by grants to the authors by the National Natural Science Foundation of China, Shanghai Rising-Star Program, Natural Science Foundation of Shanghai, Five-Year National Key R&D Program, and Ruijin–Zhongmei Huadong Lupus Funding. The authors had no disclosures. Dr. Costenbader disclosed consulting/research collaboration relationships with AstraZeneca, Amgen, Biogen, Bristol-Myers Squibb, GSK, Merck, Gilead, and Cabaletta. Dr. James and Dr. Wallace had no disclosures.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Hypnosis May Offer Relief During Sharp Debridement of Skin Ulcers
TOPLINE:
Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.
METHODOLOGY:
- Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
- They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
- Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
- Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.
TAKEAWAY:
- Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
- Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
- The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
- Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.
IN PRACTICE:
“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.
SOURCE:
The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.
LIMITATIONS:
The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.
DISCLOSURES:
The study did not have a funding source. The authors declared no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.
METHODOLOGY:
- Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
- They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
- Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
- Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.
TAKEAWAY:
- Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
- Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
- The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
- Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.
IN PRACTICE:
“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.
SOURCE:
The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.
LIMITATIONS:
The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.
DISCLOSURES:
The study did not have a funding source. The authors declared no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.
METHODOLOGY:
- Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
- They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
- Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
- Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.
TAKEAWAY:
- Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
- Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
- The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
- Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.
IN PRACTICE:
“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.
SOURCE:
The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.
LIMITATIONS:
The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.
DISCLOSURES:
The study did not have a funding source. The authors declared no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.