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Is CGM the New CBT?
Lauren is a 45-year-old corporate lawyer who managed to excel in every aspect of her life, including parenting her three children while working full-time as a corporate lawyer. A math major at Harvard, she loves data.
Suffice it to say, given that I was treating her for a thyroid condition rather than diabetes, I was a little surprised when she requested I prescribe her a FreeStyle Libre (Abbott) monitor. She explained she was struggling to lose 10 pounds, and she thought continuous glucose monitoring (CGM) would help her determine which foods were impeding her weight loss journey.
While I didn’t see much downside to acquiescing, I felt she had probably been spending too much time on Reddit. What information could CGM give someone without diabetes that couldn’t be gleaned from a food label? Nevertheless, Lauren filled the prescription and began her foray into this relatively uncharted world. When she returned for a follow-up visit several months later, I was shocked to see that she had lost her intended weight. With my tail between my legs, I decided to review the theories and science behind the use of CGM in patients without insulin resistance.
Although it’s not rocket science, CGM can help patients through a “carrot and stick” approach to dieting. Lean proteins, nonstarchy vegetables, and monounsaturated fats such as nuts and avocado all support weight loss and tend to keep blood glucose levels stable. In contrast, foods known to cause weight gain (eg, sugary foods, refined starches, and processed foods) cause sugar spikes in real time. Similarly, large portion sizes are more likely to result in sugar spikes, and pairing proteins with carbohydrates minimizes blood glucose excursions.
Though all of this is basic common sense, . And because blood glucose is influenced by myriad factors including stress, genetics and metabolism, CGM can also potentially help create personal guidance for food choices.
In addition, CGM can reveal the effect of poor sleep and stress on blood glucose levels, thereby encouraging healthier lifestyle choices. The data collected also may provide information on how different modalities of physical activity affect blood glucose levels. A recent study compared the effect of high-intensity interval training (HIIT) and continuous moderate-intensity exercise on postmeal blood glucose in overweight individuals without diabetes. CGM revealed that HIIT is more advantageous for preventing postmeal spikes.
Although CGM appears to be a sophisticated form of cognitive-behavioral therapy, I do worry that the incessant stream of information can lead to worsening anxiety, obsessive compulsive behaviors, or restrictive eating tendencies. Still, thanks to Lauren, I now believe that real-time CGM may lead to behavior modification in food selection and physical activity.
Dr. Messer, Clinical Assistant Professor, Mount Sinai School of Medicine; Associate Professor, Hofstra School of Medicine, New York, NY, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Lauren is a 45-year-old corporate lawyer who managed to excel in every aspect of her life, including parenting her three children while working full-time as a corporate lawyer. A math major at Harvard, she loves data.
Suffice it to say, given that I was treating her for a thyroid condition rather than diabetes, I was a little surprised when she requested I prescribe her a FreeStyle Libre (Abbott) monitor. She explained she was struggling to lose 10 pounds, and she thought continuous glucose monitoring (CGM) would help her determine which foods were impeding her weight loss journey.
While I didn’t see much downside to acquiescing, I felt she had probably been spending too much time on Reddit. What information could CGM give someone without diabetes that couldn’t be gleaned from a food label? Nevertheless, Lauren filled the prescription and began her foray into this relatively uncharted world. When she returned for a follow-up visit several months later, I was shocked to see that she had lost her intended weight. With my tail between my legs, I decided to review the theories and science behind the use of CGM in patients without insulin resistance.
Although it’s not rocket science, CGM can help patients through a “carrot and stick” approach to dieting. Lean proteins, nonstarchy vegetables, and monounsaturated fats such as nuts and avocado all support weight loss and tend to keep blood glucose levels stable. In contrast, foods known to cause weight gain (eg, sugary foods, refined starches, and processed foods) cause sugar spikes in real time. Similarly, large portion sizes are more likely to result in sugar spikes, and pairing proteins with carbohydrates minimizes blood glucose excursions.
Though all of this is basic common sense, . And because blood glucose is influenced by myriad factors including stress, genetics and metabolism, CGM can also potentially help create personal guidance for food choices.
In addition, CGM can reveal the effect of poor sleep and stress on blood glucose levels, thereby encouraging healthier lifestyle choices. The data collected also may provide information on how different modalities of physical activity affect blood glucose levels. A recent study compared the effect of high-intensity interval training (HIIT) and continuous moderate-intensity exercise on postmeal blood glucose in overweight individuals without diabetes. CGM revealed that HIIT is more advantageous for preventing postmeal spikes.
Although CGM appears to be a sophisticated form of cognitive-behavioral therapy, I do worry that the incessant stream of information can lead to worsening anxiety, obsessive compulsive behaviors, or restrictive eating tendencies. Still, thanks to Lauren, I now believe that real-time CGM may lead to behavior modification in food selection and physical activity.
Dr. Messer, Clinical Assistant Professor, Mount Sinai School of Medicine; Associate Professor, Hofstra School of Medicine, New York, NY, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Lauren is a 45-year-old corporate lawyer who managed to excel in every aspect of her life, including parenting her three children while working full-time as a corporate lawyer. A math major at Harvard, she loves data.
Suffice it to say, given that I was treating her for a thyroid condition rather than diabetes, I was a little surprised when she requested I prescribe her a FreeStyle Libre (Abbott) monitor. She explained she was struggling to lose 10 pounds, and she thought continuous glucose monitoring (CGM) would help her determine which foods were impeding her weight loss journey.
While I didn’t see much downside to acquiescing, I felt she had probably been spending too much time on Reddit. What information could CGM give someone without diabetes that couldn’t be gleaned from a food label? Nevertheless, Lauren filled the prescription and began her foray into this relatively uncharted world. When she returned for a follow-up visit several months later, I was shocked to see that she had lost her intended weight. With my tail between my legs, I decided to review the theories and science behind the use of CGM in patients without insulin resistance.
Although it’s not rocket science, CGM can help patients through a “carrot and stick” approach to dieting. Lean proteins, nonstarchy vegetables, and monounsaturated fats such as nuts and avocado all support weight loss and tend to keep blood glucose levels stable. In contrast, foods known to cause weight gain (eg, sugary foods, refined starches, and processed foods) cause sugar spikes in real time. Similarly, large portion sizes are more likely to result in sugar spikes, and pairing proteins with carbohydrates minimizes blood glucose excursions.
Though all of this is basic common sense, . And because blood glucose is influenced by myriad factors including stress, genetics and metabolism, CGM can also potentially help create personal guidance for food choices.
In addition, CGM can reveal the effect of poor sleep and stress on blood glucose levels, thereby encouraging healthier lifestyle choices. The data collected also may provide information on how different modalities of physical activity affect blood glucose levels. A recent study compared the effect of high-intensity interval training (HIIT) and continuous moderate-intensity exercise on postmeal blood glucose in overweight individuals without diabetes. CGM revealed that HIIT is more advantageous for preventing postmeal spikes.
Although CGM appears to be a sophisticated form of cognitive-behavioral therapy, I do worry that the incessant stream of information can lead to worsening anxiety, obsessive compulsive behaviors, or restrictive eating tendencies. Still, thanks to Lauren, I now believe that real-time CGM may lead to behavior modification in food selection and physical activity.
Dr. Messer, Clinical Assistant Professor, Mount Sinai School of Medicine; Associate Professor, Hofstra School of Medicine, New York, NY, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Therapeutic Drug Monitoring in Rheumatology: A Promising Outlook But Many Barriers to Overcome
Therapeutic drug monitoring (TDM) — the practice of using laboratory testing to measure blood levels of drugs — has garnered growing interest among rheumatologists in managing patients on disease-modifying antirheumatic drugs (DMARDs), but that hasn’t exactly translated to widespread practice.
While TDM has made some inroads with patients taking monoclonal antibodies, specifically infliximab, its uptake has encountered a number of headwinds, not the least of which is a lack of evidence and clinical guidelines, uneven access and standards of assays, and even an uncertainty about how to interpret laboratory results.
“In some fields, such as neurology, TDM is accepted for antiepileptics,” Michelle Petri, MD, MPH, director of the Johns Hopkins Lupus Center, Baltimore, told Medscape Medical News. “In rheumatology, though, TDM is underutilized and not adequately championed by the American College of Rheumatology.”
She noted that TDM is most acutely needed for management of systemic lupus erythematosus, where nonadherence is a major problem. “Whole blood hydroxychloroquine monitoring has proven beneficial for identifying nonadherence, but also to pinpoint patients who are on too much, a risk factor for retinopathy,” Petri said.
“The state of therapeutic drug monitoring in general has been interesting when you think about its use in autoimmune disease because it’s very much used in gastroenterology and it’s been much less used in rheumatology,” Zachary Wallace, MD, codirector of the Rheumatology & Allergy Clinical Epidemiology Research Center at Massachusetts General Hospital in Boston, told Medscape Medical News. “Some of that may have to do with the interpretation of the availability of evidence, but I think it’s something clinicians will come across more and more often in their practice and wondering what its role might be,” he added.
The movement to precision medicine also portends to grow interest in TDM in rheumatology, said Stephen Balevic, MD, PhD, a rheumatologist and pharmacologist at Duke University and director of pharmacometrics at the Duke Clinical Research Institute, Durham, North Carolina.
“It’s a very exciting time for rheumatologists to begin thinking outside box on what it means to study precision medicine, and I think pharmacology is one of the most overlooked aspects of precision medicine in our community,” he told Medscape Medical News.
That may be because older DMARDs, namely hydroxychloroquine and methotrexate, came to market when regulatory requirements were different than they are today, Balevic said. “Many of the older conventional DMARDs were discovered incidentally and never really had the traditional pharmacokinetic-pharmacodynamic trials to determine optimal dosing, or perhaps that was extrapolated from other populations,” he said.
So, the “one-size-fits-all” approach does not work for prescribing older or even some of the newer DMARDs for rheumatologic disorders, Balevic said.
Reactive vs Proactive TDM
Among the few trials that examined TDM in rheumatology patients are the NOR-DRUM A and B trials in Norway. Marthe Brun, MD, PhD, a rheumatologist at the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and a coauthor of the NOR-DRUM trials, told Medscape Medical News that the trials found an overall benefit to TDM during infliximab maintenance therapy. The trials included not only patients with inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) but also patients with inflammatory bowel disease and psoriasis, Brun said.
Brun explained that two types of TDM exist: Reactive and proactive. “Reactive TDM is when you use it to find the reason for a patient having a flare or disease worsening,” she told Medscape Medical News. “Proactive TDM would be regular testing to keep a patient within a therapeutic range to avoid flare because of low drug concentrations.”
Gastroenterologists are more inclined than rheumatologists and dermatologists to use reactive TDM, she said. “There have been no recommendations regarding proactive TDM because of the lack of data.”
In Europe, Wallace noted that European Alliance of Associations for Rheumatology (EULAR) recommendations consider the use of TDM in specific clinical scenarios, such as when treatment fails or to evaluate immunogenicity of a reaction, but they are limited. The American College of Rheumatology (ACR) does not have any recommendations for the use of TDM.
Based on the NOR-DRUM trials, rheumatologists in Norway have published their own guidelines for TDM for infliximab in rheumatologic disease, but they are in Norwegian and have not yet been taken up by EULAR, Brun noted. Publication of those recommendations in English is pending, she said.
“But for other subcutaneously administered TNF inhibitors, there’s a lack of data,” Brun added.
The State of the Evidence
NOR-DRUM A did not support the use of proactive TDM in the 30-week induction period as a way to improve disease remission in patients with chronic immune-mediated inflammatory disease. NOR-DRUM B, which evaluated TDM over a year, found the approach was more likely to lead to sustained disease control for that period.
Brun’s group recently published an analysis of the trials. “We did not find an overall effect during the initial phase of the treatment, the first 30 weeks,” she told Medscape Medical News.
“Then we looked at subgroups, and we found that the patients that developed antidrug antibodies [ADAs] had an effect, and ADA are associated with poorer outcomes as well as infusion reactions for patients treated with infliximab.
“So, it’s probably a benefit to be able to detect these ADA early before the patient experiences a disease flare or infusion reaction,” Brun added. “It facilitates for the clinician to take action to, for example, increase the dosing or switch therapy.”
However, the quality of the data supporting TDM in rheumatology is limited, Balevic said. “There’s very good observational data, but we have very few clinical trials that actually leverage TDM,” he said.
NOR-DRUM is the exception, he said. “Ideally, we need more of these dose-optimization trials to help guide clinical practice,” he said. But it stands alone.
Wallace noted several take-home messages from the NOR-DRUM trials, namely that using TDM to prevent ADA may be more effective during the maintenance phase of treatment than the induction phase. However, he said, the evidence is still emerging.
“It’s reasonable to say that we’re at an early stage of the evidence,” he said. “If you look at the large trials that have been done in rheumatology, they’ve combined patients with many different types of conditions, and a lot of our recommendations in rheumatology are disease-specific — in rheumatoid arthritis, in vasculitis. There’s a lack of data in specific diseases to guide or examine what the role of TDM might be.”
In the meantime, no fewer than four clinical trials evaluating TDM with tumor necrosis factor (TNF) inhibitors in rheumatologic diseases are ongoing or have completed but not yet released results, according to Wallace. Three Adalimumab Drug Optimization in Rheumatoid Arthritis trials are underway: The first is evaluating drug tapering vs disease activity score; the second is testing low or usual drug concentration; and the third is studying switches to etanercept or a non-TNF inhibitor drug (abatacept, rituximab, tocilizumab, or sarilumab) in patients failing treatment. Another trial called Tocilizumab Drug Levels to Optimized Treatment in RA is randomizing patients with high drug levels to dose maintenance or dose reduction. All four trials are sponsored by the Reade Rheumatology Research Institute, Amsterdam, the Netherlands.
Until clearer answers emerge from clinical trials, a number of barriers to and questions about the potential for TDM in rheumatology persist.
Barriers to Wider Use of TDM
“The biggest barrier with TDM is simply just a lack of what to do with the data,” Balevic said. “The clinician needs clear-cut guidance on what to do with the drug level. So, in other words, what is the target concentration for the drug? And if that target is not the goal, how should that dose be adjusted?”
The optimal drug levels, particularly for the older conventional synthetic DMARDs, simply have not been validated by clinical trials, he said.
“Different studies may report different target drug levels, and this could be due to different underlying population, or a different matrix — a measure of whole blood vs plasma — or even the timing of the sample,” he said. Balevic led a pharmacokinetic study earlier this year that proposed an algorithm for determining the number of missed hydroxychloroquine doses.
“This really goes back to the clinician needing to draw on a lot of pharmacology training to interpret the literature,” Balevic added.
That gets to the need for more education among rheumatologists, as Brun pointed out. “The physician needs to be educated about therapeutic ranges, when to assess concentrations of drug antibodies, and how to react to the results,” Brun said.
Which ADAs to identify is also problematic. “For antidrug antibodies, it’s especially challenging because there are so many assay formats in use, and it’s a bit complicated to analyze these antidrug antibodies,” Brun said. “There’s no consensus on what calibrators to use, and there’s no standardization of how to report the results, so you can’t really compare results from different assays. You need to know what your laboratory is using and how to interpret results from that particular assay, so that’s a challenge.”
Variability in drug tolerance also exists across assays, Wallace noted. “One of the challenges that have come up in the discussion of therapeutic drug monitoring is understanding what the target level is,” he said. “Defining what the target level might be for a specific condition is not something that’s well understood.”
Breaking down the science, he noted that an ADA can bind to a monoclonal antibody, forming an immune complex that avoids detection. Drug-sensitive assays may detect high concentrations of ADAs but miss low or moderate concentrations. Drug-tolerant assays may be more likely to detect low concentrations at ADAs, but the clinical significance is unclear.
Cost and Patient Trust as Barriers
“The costs vary a lot from assay to assay,” Brun said. “Some commercial assays can be really expensive.” In Norway, a dedicated lab with its own in-house assays helps to keep costs down, she said.
But that’s not the case in the United States, where insurance coverage can be a question mark, Shivani Garg, MD, a rheumatologist at the University of Wisconsin (UW)-Madison and director of the UW-Madison Health Lupus and Lupus Nephritis Clinics, told Medscape Medical News. “A lot of insurances are covering therapeutic drug monitoring, but for the high-deductible plans, there should be a way to offer these important tests to patients at a lower cost or figure out a way for coverage for those patients so that they can show that there are benefits of therapeutic drug monitoring without being sent a really big bill,” she said.
Patient trust could be another potential barrier, Garg said. “A lot of times there is not shared decision-making involved in why this test is being done, how those tests will help us as clinicians, and [patients’ understanding of] the use of the medicine,” Garg said.
“If the shared decision-making to build trust is not there, a lot of times patients worry that they’re being under surveillance or they’re being watched, so that might add to the lack of trust in the core issues that are critical threats to patients with chronic diseases because this is a lifelong partnership,” she said.
Convenience is another issue. “Particularly with mycophenolate levels, a lot of studies have used area under the curve, so getting an area under the curve level over a period of 12 hours would require several samples,” Garg said.
Testing protocols are also uncertain, Garg added. “A few data points ... are missing, like how we use the data over time,” she said. “If you do it for a given patient over several years, how often should you do it? How often do the levels fluctuate? How are the data used to inform dosing changes or monitoring changes?
“When those pieces are put together, then we are more likely to build up an intervention that clinicians can use in clinical practice, so they know how to order it and how frequently do it — every 6 months, 3 months, or every month. And then, over a period of time, how to adjust the dosing. That’s the big question.”
Who May Benefit Most From TDM?
In the NOR-DRUM trials, patients at risk of developing ADA early on, before a disease flare or infusion reaction, seemed to benefit most from TDM. But who are those patients?
“We looked at risk factors for developing antidrug antibodies, and we found that patients with high disease activity when starting treatment, smokers, and patients with rheumatoid arthritis had a higher risk than other patients, as did patients who are not using concomitant immunosuppressive therapy,” Brun said.
“During treatment, we also found that low serum drug levels and drug holidays above 11 weeks were also risk factors,” she added.
The NOR-DRUM researchers also evaluated genetic risk factors and found that patients with the HLA-DQ2 gene variant were also at increased risk of developing ADA.
While NOR-DRUM evaluated only infliximab, some of its lessons may be applied to other DMARDs, Brun said. “We think that for other subcutaneously administered TNF inhibitors, you would probably see the same effect of proactive TDM, but we currently do not have data on that,” she said. A study similar to the NOR-DRUM design will evaluate this in Norway, Brun added.
She explained why the findings with infliximab may extend to adalimumab, which may be the second most immunogenic TNF inhibitor after infliximab. “The administration is different; it’s administered more often than infliximab; that would also make the results more uncertain to generalize to the other treatments, but I would guess there are also benefits of using TDM in other treatments.”
Potential Risks for TDM
Wallace has noted that TDM, with the current state of evidence, carries a number of potential risks. “The potential risks might be that you unnecessarily discontinue a medication because you detected an antibody, or the level seems low and you’re not able to get it higher, but the patient is otherwise doing fine,” he said. “You might end up increasing doses of the medicine that would put the patient at potentially increased risk of infection, as well as obviously more costs.”
That would also lead to more utilization of resources and costs, he said. “Some of those reasons are why there has been hesitation with therapeutic drug monitoring,” Wallace added.
A number of questions also surround the use of biosimilars and ADA levels, Wallace said. While a review of clinical trials found no meaningful differences in terms of immunogenicity between biosimilars and reference products, it did note discrepancies in how the agents were evaluated.
What DMARDs Are Most Suitable for TDM?
Petri said TDM would be useful for monitoring patients on mycophenolate mofetil. “A trough level can at least tell us if a patient is taking it,” she said. “Tacrolimus, used for lupus nephritis, has well-accepted peak and trough trends due to widespread use in transplant.”
Drugs with a wide variability in pharmacokinetics may also be suitable for TDM, Balevic said. That would include hydroxychloroquine, azathioprine, mycophenolate, or even cyclophosphamide. Drugs that have a narrow therapeutic index, such as tacrolimus, cyclosporine, or again, cyclophosphamide, might also be amenable to TDM, he said.
Why Do TDM?
“The two main reasons why somebody would go on to detect drug levels: The first may be to assess medication adherence, and this applies virtually to any drug that rheumatologists use; the second reason is to optimize dozing, either for efficacy purposes or to prevent toxicity,” Balevic said.
“When it comes to optimizing dosing, you should really think about TDM as one tool in our toolbelt,” he said.
Dose is “just a surrogate,” he said. “When we prescribe a drug, what truly matters is the amount of active unbound drug at the site of action. That’s what’s responsible for a drug’s pharmacologic effect.”
However, the same dose, or even the same weight-based dose, does not necessarily mean similar patients will achieve the same amount of exposure to the drug, but TDM can help determine that, he said.
What’s Next
Studies into the use of TDM in rheumatology are ongoing. Brun said her group is currently conducting a cost-effective analysis from the NOR-DRUM trials.
“There’s going to be more studies coming out in the next few years, looking at what impact the use of therapeutic drug monitoring might have on outcomes,” Wallace said.
“As we accumulate more and more evidence, we might see organizations like ACR and EULAR start to weigh in more on whether or not therapeutic drug monitoring can or should be used.”
Petri, Brun, and Garg had no relevant disclosures. Wallace disclosed financial relationships with Amgen, Alexion, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Medpace, Novartis, Sanofi, Viela Bio, Visterra, Xencor, and Zenas. Balevic disclosed relationships with the National Institutes of Health, the Childhood Arthritis and Rheumatology Research Alliance, and UCB.
A version of this article appeared on Medscape.com.
Therapeutic drug monitoring (TDM) — the practice of using laboratory testing to measure blood levels of drugs — has garnered growing interest among rheumatologists in managing patients on disease-modifying antirheumatic drugs (DMARDs), but that hasn’t exactly translated to widespread practice.
While TDM has made some inroads with patients taking monoclonal antibodies, specifically infliximab, its uptake has encountered a number of headwinds, not the least of which is a lack of evidence and clinical guidelines, uneven access and standards of assays, and even an uncertainty about how to interpret laboratory results.
“In some fields, such as neurology, TDM is accepted for antiepileptics,” Michelle Petri, MD, MPH, director of the Johns Hopkins Lupus Center, Baltimore, told Medscape Medical News. “In rheumatology, though, TDM is underutilized and not adequately championed by the American College of Rheumatology.”
She noted that TDM is most acutely needed for management of systemic lupus erythematosus, where nonadherence is a major problem. “Whole blood hydroxychloroquine monitoring has proven beneficial for identifying nonadherence, but also to pinpoint patients who are on too much, a risk factor for retinopathy,” Petri said.
“The state of therapeutic drug monitoring in general has been interesting when you think about its use in autoimmune disease because it’s very much used in gastroenterology and it’s been much less used in rheumatology,” Zachary Wallace, MD, codirector of the Rheumatology & Allergy Clinical Epidemiology Research Center at Massachusetts General Hospital in Boston, told Medscape Medical News. “Some of that may have to do with the interpretation of the availability of evidence, but I think it’s something clinicians will come across more and more often in their practice and wondering what its role might be,” he added.
The movement to precision medicine also portends to grow interest in TDM in rheumatology, said Stephen Balevic, MD, PhD, a rheumatologist and pharmacologist at Duke University and director of pharmacometrics at the Duke Clinical Research Institute, Durham, North Carolina.
“It’s a very exciting time for rheumatologists to begin thinking outside box on what it means to study precision medicine, and I think pharmacology is one of the most overlooked aspects of precision medicine in our community,” he told Medscape Medical News.
That may be because older DMARDs, namely hydroxychloroquine and methotrexate, came to market when regulatory requirements were different than they are today, Balevic said. “Many of the older conventional DMARDs were discovered incidentally and never really had the traditional pharmacokinetic-pharmacodynamic trials to determine optimal dosing, or perhaps that was extrapolated from other populations,” he said.
So, the “one-size-fits-all” approach does not work for prescribing older or even some of the newer DMARDs for rheumatologic disorders, Balevic said.
Reactive vs Proactive TDM
Among the few trials that examined TDM in rheumatology patients are the NOR-DRUM A and B trials in Norway. Marthe Brun, MD, PhD, a rheumatologist at the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and a coauthor of the NOR-DRUM trials, told Medscape Medical News that the trials found an overall benefit to TDM during infliximab maintenance therapy. The trials included not only patients with inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) but also patients with inflammatory bowel disease and psoriasis, Brun said.
Brun explained that two types of TDM exist: Reactive and proactive. “Reactive TDM is when you use it to find the reason for a patient having a flare or disease worsening,” she told Medscape Medical News. “Proactive TDM would be regular testing to keep a patient within a therapeutic range to avoid flare because of low drug concentrations.”
Gastroenterologists are more inclined than rheumatologists and dermatologists to use reactive TDM, she said. “There have been no recommendations regarding proactive TDM because of the lack of data.”
In Europe, Wallace noted that European Alliance of Associations for Rheumatology (EULAR) recommendations consider the use of TDM in specific clinical scenarios, such as when treatment fails or to evaluate immunogenicity of a reaction, but they are limited. The American College of Rheumatology (ACR) does not have any recommendations for the use of TDM.
Based on the NOR-DRUM trials, rheumatologists in Norway have published their own guidelines for TDM for infliximab in rheumatologic disease, but they are in Norwegian and have not yet been taken up by EULAR, Brun noted. Publication of those recommendations in English is pending, she said.
“But for other subcutaneously administered TNF inhibitors, there’s a lack of data,” Brun added.
The State of the Evidence
NOR-DRUM A did not support the use of proactive TDM in the 30-week induction period as a way to improve disease remission in patients with chronic immune-mediated inflammatory disease. NOR-DRUM B, which evaluated TDM over a year, found the approach was more likely to lead to sustained disease control for that period.
Brun’s group recently published an analysis of the trials. “We did not find an overall effect during the initial phase of the treatment, the first 30 weeks,” she told Medscape Medical News.
“Then we looked at subgroups, and we found that the patients that developed antidrug antibodies [ADAs] had an effect, and ADA are associated with poorer outcomes as well as infusion reactions for patients treated with infliximab.
“So, it’s probably a benefit to be able to detect these ADA early before the patient experiences a disease flare or infusion reaction,” Brun added. “It facilitates for the clinician to take action to, for example, increase the dosing or switch therapy.”
However, the quality of the data supporting TDM in rheumatology is limited, Balevic said. “There’s very good observational data, but we have very few clinical trials that actually leverage TDM,” he said.
NOR-DRUM is the exception, he said. “Ideally, we need more of these dose-optimization trials to help guide clinical practice,” he said. But it stands alone.
Wallace noted several take-home messages from the NOR-DRUM trials, namely that using TDM to prevent ADA may be more effective during the maintenance phase of treatment than the induction phase. However, he said, the evidence is still emerging.
“It’s reasonable to say that we’re at an early stage of the evidence,” he said. “If you look at the large trials that have been done in rheumatology, they’ve combined patients with many different types of conditions, and a lot of our recommendations in rheumatology are disease-specific — in rheumatoid arthritis, in vasculitis. There’s a lack of data in specific diseases to guide or examine what the role of TDM might be.”
In the meantime, no fewer than four clinical trials evaluating TDM with tumor necrosis factor (TNF) inhibitors in rheumatologic diseases are ongoing or have completed but not yet released results, according to Wallace. Three Adalimumab Drug Optimization in Rheumatoid Arthritis trials are underway: The first is evaluating drug tapering vs disease activity score; the second is testing low or usual drug concentration; and the third is studying switches to etanercept or a non-TNF inhibitor drug (abatacept, rituximab, tocilizumab, or sarilumab) in patients failing treatment. Another trial called Tocilizumab Drug Levels to Optimized Treatment in RA is randomizing patients with high drug levels to dose maintenance or dose reduction. All four trials are sponsored by the Reade Rheumatology Research Institute, Amsterdam, the Netherlands.
Until clearer answers emerge from clinical trials, a number of barriers to and questions about the potential for TDM in rheumatology persist.
Barriers to Wider Use of TDM
“The biggest barrier with TDM is simply just a lack of what to do with the data,” Balevic said. “The clinician needs clear-cut guidance on what to do with the drug level. So, in other words, what is the target concentration for the drug? And if that target is not the goal, how should that dose be adjusted?”
The optimal drug levels, particularly for the older conventional synthetic DMARDs, simply have not been validated by clinical trials, he said.
“Different studies may report different target drug levels, and this could be due to different underlying population, or a different matrix — a measure of whole blood vs plasma — or even the timing of the sample,” he said. Balevic led a pharmacokinetic study earlier this year that proposed an algorithm for determining the number of missed hydroxychloroquine doses.
“This really goes back to the clinician needing to draw on a lot of pharmacology training to interpret the literature,” Balevic added.
That gets to the need for more education among rheumatologists, as Brun pointed out. “The physician needs to be educated about therapeutic ranges, when to assess concentrations of drug antibodies, and how to react to the results,” Brun said.
Which ADAs to identify is also problematic. “For antidrug antibodies, it’s especially challenging because there are so many assay formats in use, and it’s a bit complicated to analyze these antidrug antibodies,” Brun said. “There’s no consensus on what calibrators to use, and there’s no standardization of how to report the results, so you can’t really compare results from different assays. You need to know what your laboratory is using and how to interpret results from that particular assay, so that’s a challenge.”
Variability in drug tolerance also exists across assays, Wallace noted. “One of the challenges that have come up in the discussion of therapeutic drug monitoring is understanding what the target level is,” he said. “Defining what the target level might be for a specific condition is not something that’s well understood.”
Breaking down the science, he noted that an ADA can bind to a monoclonal antibody, forming an immune complex that avoids detection. Drug-sensitive assays may detect high concentrations of ADAs but miss low or moderate concentrations. Drug-tolerant assays may be more likely to detect low concentrations at ADAs, but the clinical significance is unclear.
Cost and Patient Trust as Barriers
“The costs vary a lot from assay to assay,” Brun said. “Some commercial assays can be really expensive.” In Norway, a dedicated lab with its own in-house assays helps to keep costs down, she said.
But that’s not the case in the United States, where insurance coverage can be a question mark, Shivani Garg, MD, a rheumatologist at the University of Wisconsin (UW)-Madison and director of the UW-Madison Health Lupus and Lupus Nephritis Clinics, told Medscape Medical News. “A lot of insurances are covering therapeutic drug monitoring, but for the high-deductible plans, there should be a way to offer these important tests to patients at a lower cost or figure out a way for coverage for those patients so that they can show that there are benefits of therapeutic drug monitoring without being sent a really big bill,” she said.
Patient trust could be another potential barrier, Garg said. “A lot of times there is not shared decision-making involved in why this test is being done, how those tests will help us as clinicians, and [patients’ understanding of] the use of the medicine,” Garg said.
“If the shared decision-making to build trust is not there, a lot of times patients worry that they’re being under surveillance or they’re being watched, so that might add to the lack of trust in the core issues that are critical threats to patients with chronic diseases because this is a lifelong partnership,” she said.
Convenience is another issue. “Particularly with mycophenolate levels, a lot of studies have used area under the curve, so getting an area under the curve level over a period of 12 hours would require several samples,” Garg said.
Testing protocols are also uncertain, Garg added. “A few data points ... are missing, like how we use the data over time,” she said. “If you do it for a given patient over several years, how often should you do it? How often do the levels fluctuate? How are the data used to inform dosing changes or monitoring changes?
“When those pieces are put together, then we are more likely to build up an intervention that clinicians can use in clinical practice, so they know how to order it and how frequently do it — every 6 months, 3 months, or every month. And then, over a period of time, how to adjust the dosing. That’s the big question.”
Who May Benefit Most From TDM?
In the NOR-DRUM trials, patients at risk of developing ADA early on, before a disease flare or infusion reaction, seemed to benefit most from TDM. But who are those patients?
“We looked at risk factors for developing antidrug antibodies, and we found that patients with high disease activity when starting treatment, smokers, and patients with rheumatoid arthritis had a higher risk than other patients, as did patients who are not using concomitant immunosuppressive therapy,” Brun said.
“During treatment, we also found that low serum drug levels and drug holidays above 11 weeks were also risk factors,” she added.
The NOR-DRUM researchers also evaluated genetic risk factors and found that patients with the HLA-DQ2 gene variant were also at increased risk of developing ADA.
While NOR-DRUM evaluated only infliximab, some of its lessons may be applied to other DMARDs, Brun said. “We think that for other subcutaneously administered TNF inhibitors, you would probably see the same effect of proactive TDM, but we currently do not have data on that,” she said. A study similar to the NOR-DRUM design will evaluate this in Norway, Brun added.
She explained why the findings with infliximab may extend to adalimumab, which may be the second most immunogenic TNF inhibitor after infliximab. “The administration is different; it’s administered more often than infliximab; that would also make the results more uncertain to generalize to the other treatments, but I would guess there are also benefits of using TDM in other treatments.”
Potential Risks for TDM
Wallace has noted that TDM, with the current state of evidence, carries a number of potential risks. “The potential risks might be that you unnecessarily discontinue a medication because you detected an antibody, or the level seems low and you’re not able to get it higher, but the patient is otherwise doing fine,” he said. “You might end up increasing doses of the medicine that would put the patient at potentially increased risk of infection, as well as obviously more costs.”
That would also lead to more utilization of resources and costs, he said. “Some of those reasons are why there has been hesitation with therapeutic drug monitoring,” Wallace added.
A number of questions also surround the use of biosimilars and ADA levels, Wallace said. While a review of clinical trials found no meaningful differences in terms of immunogenicity between biosimilars and reference products, it did note discrepancies in how the agents were evaluated.
What DMARDs Are Most Suitable for TDM?
Petri said TDM would be useful for monitoring patients on mycophenolate mofetil. “A trough level can at least tell us if a patient is taking it,” she said. “Tacrolimus, used for lupus nephritis, has well-accepted peak and trough trends due to widespread use in transplant.”
Drugs with a wide variability in pharmacokinetics may also be suitable for TDM, Balevic said. That would include hydroxychloroquine, azathioprine, mycophenolate, or even cyclophosphamide. Drugs that have a narrow therapeutic index, such as tacrolimus, cyclosporine, or again, cyclophosphamide, might also be amenable to TDM, he said.
Why Do TDM?
“The two main reasons why somebody would go on to detect drug levels: The first may be to assess medication adherence, and this applies virtually to any drug that rheumatologists use; the second reason is to optimize dozing, either for efficacy purposes or to prevent toxicity,” Balevic said.
“When it comes to optimizing dosing, you should really think about TDM as one tool in our toolbelt,” he said.
Dose is “just a surrogate,” he said. “When we prescribe a drug, what truly matters is the amount of active unbound drug at the site of action. That’s what’s responsible for a drug’s pharmacologic effect.”
However, the same dose, or even the same weight-based dose, does not necessarily mean similar patients will achieve the same amount of exposure to the drug, but TDM can help determine that, he said.
What’s Next
Studies into the use of TDM in rheumatology are ongoing. Brun said her group is currently conducting a cost-effective analysis from the NOR-DRUM trials.
“There’s going to be more studies coming out in the next few years, looking at what impact the use of therapeutic drug monitoring might have on outcomes,” Wallace said.
“As we accumulate more and more evidence, we might see organizations like ACR and EULAR start to weigh in more on whether or not therapeutic drug monitoring can or should be used.”
Petri, Brun, and Garg had no relevant disclosures. Wallace disclosed financial relationships with Amgen, Alexion, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Medpace, Novartis, Sanofi, Viela Bio, Visterra, Xencor, and Zenas. Balevic disclosed relationships with the National Institutes of Health, the Childhood Arthritis and Rheumatology Research Alliance, and UCB.
A version of this article appeared on Medscape.com.
Therapeutic drug monitoring (TDM) — the practice of using laboratory testing to measure blood levels of drugs — has garnered growing interest among rheumatologists in managing patients on disease-modifying antirheumatic drugs (DMARDs), but that hasn’t exactly translated to widespread practice.
While TDM has made some inroads with patients taking monoclonal antibodies, specifically infliximab, its uptake has encountered a number of headwinds, not the least of which is a lack of evidence and clinical guidelines, uneven access and standards of assays, and even an uncertainty about how to interpret laboratory results.
“In some fields, such as neurology, TDM is accepted for antiepileptics,” Michelle Petri, MD, MPH, director of the Johns Hopkins Lupus Center, Baltimore, told Medscape Medical News. “In rheumatology, though, TDM is underutilized and not adequately championed by the American College of Rheumatology.”
She noted that TDM is most acutely needed for management of systemic lupus erythematosus, where nonadherence is a major problem. “Whole blood hydroxychloroquine monitoring has proven beneficial for identifying nonadherence, but also to pinpoint patients who are on too much, a risk factor for retinopathy,” Petri said.
“The state of therapeutic drug monitoring in general has been interesting when you think about its use in autoimmune disease because it’s very much used in gastroenterology and it’s been much less used in rheumatology,” Zachary Wallace, MD, codirector of the Rheumatology & Allergy Clinical Epidemiology Research Center at Massachusetts General Hospital in Boston, told Medscape Medical News. “Some of that may have to do with the interpretation of the availability of evidence, but I think it’s something clinicians will come across more and more often in their practice and wondering what its role might be,” he added.
The movement to precision medicine also portends to grow interest in TDM in rheumatology, said Stephen Balevic, MD, PhD, a rheumatologist and pharmacologist at Duke University and director of pharmacometrics at the Duke Clinical Research Institute, Durham, North Carolina.
“It’s a very exciting time for rheumatologists to begin thinking outside box on what it means to study precision medicine, and I think pharmacology is one of the most overlooked aspects of precision medicine in our community,” he told Medscape Medical News.
That may be because older DMARDs, namely hydroxychloroquine and methotrexate, came to market when regulatory requirements were different than they are today, Balevic said. “Many of the older conventional DMARDs were discovered incidentally and never really had the traditional pharmacokinetic-pharmacodynamic trials to determine optimal dosing, or perhaps that was extrapolated from other populations,” he said.
So, the “one-size-fits-all” approach does not work for prescribing older or even some of the newer DMARDs for rheumatologic disorders, Balevic said.
Reactive vs Proactive TDM
Among the few trials that examined TDM in rheumatology patients are the NOR-DRUM A and B trials in Norway. Marthe Brun, MD, PhD, a rheumatologist at the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and a coauthor of the NOR-DRUM trials, told Medscape Medical News that the trials found an overall benefit to TDM during infliximab maintenance therapy. The trials included not only patients with inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) but also patients with inflammatory bowel disease and psoriasis, Brun said.
Brun explained that two types of TDM exist: Reactive and proactive. “Reactive TDM is when you use it to find the reason for a patient having a flare or disease worsening,” she told Medscape Medical News. “Proactive TDM would be regular testing to keep a patient within a therapeutic range to avoid flare because of low drug concentrations.”
Gastroenterologists are more inclined than rheumatologists and dermatologists to use reactive TDM, she said. “There have been no recommendations regarding proactive TDM because of the lack of data.”
In Europe, Wallace noted that European Alliance of Associations for Rheumatology (EULAR) recommendations consider the use of TDM in specific clinical scenarios, such as when treatment fails or to evaluate immunogenicity of a reaction, but they are limited. The American College of Rheumatology (ACR) does not have any recommendations for the use of TDM.
Based on the NOR-DRUM trials, rheumatologists in Norway have published their own guidelines for TDM for infliximab in rheumatologic disease, but they are in Norwegian and have not yet been taken up by EULAR, Brun noted. Publication of those recommendations in English is pending, she said.
“But for other subcutaneously administered TNF inhibitors, there’s a lack of data,” Brun added.
The State of the Evidence
NOR-DRUM A did not support the use of proactive TDM in the 30-week induction period as a way to improve disease remission in patients with chronic immune-mediated inflammatory disease. NOR-DRUM B, which evaluated TDM over a year, found the approach was more likely to lead to sustained disease control for that period.
Brun’s group recently published an analysis of the trials. “We did not find an overall effect during the initial phase of the treatment, the first 30 weeks,” she told Medscape Medical News.
“Then we looked at subgroups, and we found that the patients that developed antidrug antibodies [ADAs] had an effect, and ADA are associated with poorer outcomes as well as infusion reactions for patients treated with infliximab.
“So, it’s probably a benefit to be able to detect these ADA early before the patient experiences a disease flare or infusion reaction,” Brun added. “It facilitates for the clinician to take action to, for example, increase the dosing or switch therapy.”
However, the quality of the data supporting TDM in rheumatology is limited, Balevic said. “There’s very good observational data, but we have very few clinical trials that actually leverage TDM,” he said.
NOR-DRUM is the exception, he said. “Ideally, we need more of these dose-optimization trials to help guide clinical practice,” he said. But it stands alone.
Wallace noted several take-home messages from the NOR-DRUM trials, namely that using TDM to prevent ADA may be more effective during the maintenance phase of treatment than the induction phase. However, he said, the evidence is still emerging.
“It’s reasonable to say that we’re at an early stage of the evidence,” he said. “If you look at the large trials that have been done in rheumatology, they’ve combined patients with many different types of conditions, and a lot of our recommendations in rheumatology are disease-specific — in rheumatoid arthritis, in vasculitis. There’s a lack of data in specific diseases to guide or examine what the role of TDM might be.”
In the meantime, no fewer than four clinical trials evaluating TDM with tumor necrosis factor (TNF) inhibitors in rheumatologic diseases are ongoing or have completed but not yet released results, according to Wallace. Three Adalimumab Drug Optimization in Rheumatoid Arthritis trials are underway: The first is evaluating drug tapering vs disease activity score; the second is testing low or usual drug concentration; and the third is studying switches to etanercept or a non-TNF inhibitor drug (abatacept, rituximab, tocilizumab, or sarilumab) in patients failing treatment. Another trial called Tocilizumab Drug Levels to Optimized Treatment in RA is randomizing patients with high drug levels to dose maintenance or dose reduction. All four trials are sponsored by the Reade Rheumatology Research Institute, Amsterdam, the Netherlands.
Until clearer answers emerge from clinical trials, a number of barriers to and questions about the potential for TDM in rheumatology persist.
Barriers to Wider Use of TDM
“The biggest barrier with TDM is simply just a lack of what to do with the data,” Balevic said. “The clinician needs clear-cut guidance on what to do with the drug level. So, in other words, what is the target concentration for the drug? And if that target is not the goal, how should that dose be adjusted?”
The optimal drug levels, particularly for the older conventional synthetic DMARDs, simply have not been validated by clinical trials, he said.
“Different studies may report different target drug levels, and this could be due to different underlying population, or a different matrix — a measure of whole blood vs plasma — or even the timing of the sample,” he said. Balevic led a pharmacokinetic study earlier this year that proposed an algorithm for determining the number of missed hydroxychloroquine doses.
“This really goes back to the clinician needing to draw on a lot of pharmacology training to interpret the literature,” Balevic added.
That gets to the need for more education among rheumatologists, as Brun pointed out. “The physician needs to be educated about therapeutic ranges, when to assess concentrations of drug antibodies, and how to react to the results,” Brun said.
Which ADAs to identify is also problematic. “For antidrug antibodies, it’s especially challenging because there are so many assay formats in use, and it’s a bit complicated to analyze these antidrug antibodies,” Brun said. “There’s no consensus on what calibrators to use, and there’s no standardization of how to report the results, so you can’t really compare results from different assays. You need to know what your laboratory is using and how to interpret results from that particular assay, so that’s a challenge.”
Variability in drug tolerance also exists across assays, Wallace noted. “One of the challenges that have come up in the discussion of therapeutic drug monitoring is understanding what the target level is,” he said. “Defining what the target level might be for a specific condition is not something that’s well understood.”
Breaking down the science, he noted that an ADA can bind to a monoclonal antibody, forming an immune complex that avoids detection. Drug-sensitive assays may detect high concentrations of ADAs but miss low or moderate concentrations. Drug-tolerant assays may be more likely to detect low concentrations at ADAs, but the clinical significance is unclear.
Cost and Patient Trust as Barriers
“The costs vary a lot from assay to assay,” Brun said. “Some commercial assays can be really expensive.” In Norway, a dedicated lab with its own in-house assays helps to keep costs down, she said.
But that’s not the case in the United States, where insurance coverage can be a question mark, Shivani Garg, MD, a rheumatologist at the University of Wisconsin (UW)-Madison and director of the UW-Madison Health Lupus and Lupus Nephritis Clinics, told Medscape Medical News. “A lot of insurances are covering therapeutic drug monitoring, but for the high-deductible plans, there should be a way to offer these important tests to patients at a lower cost or figure out a way for coverage for those patients so that they can show that there are benefits of therapeutic drug monitoring without being sent a really big bill,” she said.
Patient trust could be another potential barrier, Garg said. “A lot of times there is not shared decision-making involved in why this test is being done, how those tests will help us as clinicians, and [patients’ understanding of] the use of the medicine,” Garg said.
“If the shared decision-making to build trust is not there, a lot of times patients worry that they’re being under surveillance or they’re being watched, so that might add to the lack of trust in the core issues that are critical threats to patients with chronic diseases because this is a lifelong partnership,” she said.
Convenience is another issue. “Particularly with mycophenolate levels, a lot of studies have used area under the curve, so getting an area under the curve level over a period of 12 hours would require several samples,” Garg said.
Testing protocols are also uncertain, Garg added. “A few data points ... are missing, like how we use the data over time,” she said. “If you do it for a given patient over several years, how often should you do it? How often do the levels fluctuate? How are the data used to inform dosing changes or monitoring changes?
“When those pieces are put together, then we are more likely to build up an intervention that clinicians can use in clinical practice, so they know how to order it and how frequently do it — every 6 months, 3 months, or every month. And then, over a period of time, how to adjust the dosing. That’s the big question.”
Who May Benefit Most From TDM?
In the NOR-DRUM trials, patients at risk of developing ADA early on, before a disease flare or infusion reaction, seemed to benefit most from TDM. But who are those patients?
“We looked at risk factors for developing antidrug antibodies, and we found that patients with high disease activity when starting treatment, smokers, and patients with rheumatoid arthritis had a higher risk than other patients, as did patients who are not using concomitant immunosuppressive therapy,” Brun said.
“During treatment, we also found that low serum drug levels and drug holidays above 11 weeks were also risk factors,” she added.
The NOR-DRUM researchers also evaluated genetic risk factors and found that patients with the HLA-DQ2 gene variant were also at increased risk of developing ADA.
While NOR-DRUM evaluated only infliximab, some of its lessons may be applied to other DMARDs, Brun said. “We think that for other subcutaneously administered TNF inhibitors, you would probably see the same effect of proactive TDM, but we currently do not have data on that,” she said. A study similar to the NOR-DRUM design will evaluate this in Norway, Brun added.
She explained why the findings with infliximab may extend to adalimumab, which may be the second most immunogenic TNF inhibitor after infliximab. “The administration is different; it’s administered more often than infliximab; that would also make the results more uncertain to generalize to the other treatments, but I would guess there are also benefits of using TDM in other treatments.”
Potential Risks for TDM
Wallace has noted that TDM, with the current state of evidence, carries a number of potential risks. “The potential risks might be that you unnecessarily discontinue a medication because you detected an antibody, or the level seems low and you’re not able to get it higher, but the patient is otherwise doing fine,” he said. “You might end up increasing doses of the medicine that would put the patient at potentially increased risk of infection, as well as obviously more costs.”
That would also lead to more utilization of resources and costs, he said. “Some of those reasons are why there has been hesitation with therapeutic drug monitoring,” Wallace added.
A number of questions also surround the use of biosimilars and ADA levels, Wallace said. While a review of clinical trials found no meaningful differences in terms of immunogenicity between biosimilars and reference products, it did note discrepancies in how the agents were evaluated.
What DMARDs Are Most Suitable for TDM?
Petri said TDM would be useful for monitoring patients on mycophenolate mofetil. “A trough level can at least tell us if a patient is taking it,” she said. “Tacrolimus, used for lupus nephritis, has well-accepted peak and trough trends due to widespread use in transplant.”
Drugs with a wide variability in pharmacokinetics may also be suitable for TDM, Balevic said. That would include hydroxychloroquine, azathioprine, mycophenolate, or even cyclophosphamide. Drugs that have a narrow therapeutic index, such as tacrolimus, cyclosporine, or again, cyclophosphamide, might also be amenable to TDM, he said.
Why Do TDM?
“The two main reasons why somebody would go on to detect drug levels: The first may be to assess medication adherence, and this applies virtually to any drug that rheumatologists use; the second reason is to optimize dozing, either for efficacy purposes or to prevent toxicity,” Balevic said.
“When it comes to optimizing dosing, you should really think about TDM as one tool in our toolbelt,” he said.
Dose is “just a surrogate,” he said. “When we prescribe a drug, what truly matters is the amount of active unbound drug at the site of action. That’s what’s responsible for a drug’s pharmacologic effect.”
However, the same dose, or even the same weight-based dose, does not necessarily mean similar patients will achieve the same amount of exposure to the drug, but TDM can help determine that, he said.
What’s Next
Studies into the use of TDM in rheumatology are ongoing. Brun said her group is currently conducting a cost-effective analysis from the NOR-DRUM trials.
“There’s going to be more studies coming out in the next few years, looking at what impact the use of therapeutic drug monitoring might have on outcomes,” Wallace said.
“As we accumulate more and more evidence, we might see organizations like ACR and EULAR start to weigh in more on whether or not therapeutic drug monitoring can or should be used.”
Petri, Brun, and Garg had no relevant disclosures. Wallace disclosed financial relationships with Amgen, Alexion, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Medpace, Novartis, Sanofi, Viela Bio, Visterra, Xencor, and Zenas. Balevic disclosed relationships with the National Institutes of Health, the Childhood Arthritis and Rheumatology Research Alliance, and UCB.
A version of this article appeared on Medscape.com.
Cannabis in Cancer: What Oncologists and Patients Should Know
first, and oncologists may be hesitant to broach the topic with their patients.
Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.
According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.
Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.
“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”
But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.
So, “let yourself off the hook,” Worster urged.
Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.
Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
Evidence on Cannabis During Cancer Care
A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.
In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.
Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.
The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.
The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.
The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.
Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.
There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.
The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
Talking to Patients About Cannabis
Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.
To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.
One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.
The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.
But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”
Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.
Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.
It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.
CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.
Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.
The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”
Worster disclosed that she is a medical consultant for EO Care.
A version of this article appeared on Medscape.com.
first, and oncologists may be hesitant to broach the topic with their patients.
Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.
According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.
Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.
“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”
But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.
So, “let yourself off the hook,” Worster urged.
Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.
Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
Evidence on Cannabis During Cancer Care
A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.
In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.
Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.
The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.
The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.
The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.
Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.
There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.
The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
Talking to Patients About Cannabis
Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.
To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.
One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.
The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.
But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”
Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.
Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.
It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.
CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.
Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.
The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”
Worster disclosed that she is a medical consultant for EO Care.
A version of this article appeared on Medscape.com.
first, and oncologists may be hesitant to broach the topic with their patients.
Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.
According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.
Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.
“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”
But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.
So, “let yourself off the hook,” Worster urged.
Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.
Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
Evidence on Cannabis During Cancer Care
A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.
In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.
Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.
The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.
The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.
The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.
Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.
There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.
The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
Talking to Patients About Cannabis
Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.
To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.
One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.
The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.
But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”
Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.
Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.
It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.
CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.
Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.
The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”
Worster disclosed that she is a medical consultant for EO Care.
A version of this article appeared on Medscape.com.
Few Differences Seen in RA Pain Outcomes for JAK Inhibitors, Biologics
TOPLINE:
Janus kinase (JAK) inhibitors had a marginally superior effect on pain relief when compared with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA), particularly when used as monotherapy and in those previously treated with at least two biologic disease-modifying antirheumatic drugs (DMARDs), but their pain reduction effects were similar to those of non–TNF inhibitor biologic DMARDs.
METHODOLOGY:
- Researchers aimed to compare the effect of JAK inhibitors and each class of biologic DMARDs such as TNF inhibitors, rituximab, abatacept, and interleukin (IL)-6 inhibitors on pain in patients with RA in clinical practice.
- They included 8430 patients with RA who were initiated on either a JAK inhibitor (n = 1827), TNF inhibitor (n = 6422), IL-6 inhibitor (n = 887), abatacept (n = 1102), or rituximab (n = 1149) in 2017-2019.
- Differences in the change in pain, assessed using a visual analog scale (VAS; 0-100 mm), from baseline to 3 months were compared between the treatment arms.
- The proportion of patients who continued their initial treatment with low pain levels (VAS pain, < 20 mm) at 12 months was also evaluated.
- The comparisons of treatment responses between JAK inhibitors and biologic DMARDs were analyzed using multivariate linear regression, adjusted for patient characteristics, comorbidities, current co-medication, and previous treatment.
TAKEAWAY:
- Pain scores improved from baseline to 3 months in all the treatment arms, with mean changes ranging from −20.1 mm (95% CI, −23.1 to −17.2) for IL-6 inhibitors to −16.6 mm (95% CI, −19.1 to −14.0) for rituximab.
- At 3 months, JAK inhibitors reduced pain scores by 4.0 mm (95% CI, 1.7-6.3) more than TNF inhibitors and by 3.9 mm (95% CI, 0.9-6.9) more than rituximab; however, the change in pain was not significantly different on comparing JAK inhibitors with abatacept or IL-6 inhibitors.
- The superior pain-reducing effects of JAK inhibitors over those of TNF inhibitors were more prominent in those who were previously treated with at least two biologic DMARDs and when the treatments were used as monotherapy.
- At 12 months, 19.5% of the patients receiving JAK inhibitors continued their treatment and achieved low pain levels, with the corresponding proportions ranging from 17% to 26% for biologic DMARDs; JAK inhibitors were more effective in reducing pain than TNF inhibitors, although the difference was not statistically significant.
IN PRACTICE:
“JAK inhibitors yield slightly better pain outcomes than TNF inhibitors. The magnitude of these effects is unlikely to be clinically meaningful in unselected groups of patients with RA,” experts from Feinberg School of Medicine, Northwestern University, Chicago, wrote in an accompanying editorial. “Specific subgroups, such as those who have tried at least two DMARDs, may experience greater effects,” they added.
SOURCE:
The study was led by Anna Eberhard, MD, Department of Clinical Sciences, Lund University, Malmö, Sweden. It was published online on September 22, 2024, in Arthritis & Rheumatology.
LIMITATIONS:
The study had a significant amount of missing data, particularly for follow-up evaluations, which may have introduced bias. The majority of patients were treated using baricitinib, potentially limiting the generalizability to other JAK inhibitors. Residual confounding could not be excluded despite adjustments for multiple relevant patient characteristics.
DISCLOSURES:
This study was supported by grants from The Swedish Research Council, The Swedish Rheumatism Association, and Lund University. Some authors declared receiving consulting fees, payments or honoraria, or grants or having other ties with pharmaceutical companies and other sources.
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:
Janus kinase (JAK) inhibitors had a marginally superior effect on pain relief when compared with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA), particularly when used as monotherapy and in those previously treated with at least two biologic disease-modifying antirheumatic drugs (DMARDs), but their pain reduction effects were similar to those of non–TNF inhibitor biologic DMARDs.
METHODOLOGY:
- Researchers aimed to compare the effect of JAK inhibitors and each class of biologic DMARDs such as TNF inhibitors, rituximab, abatacept, and interleukin (IL)-6 inhibitors on pain in patients with RA in clinical practice.
- They included 8430 patients with RA who were initiated on either a JAK inhibitor (n = 1827), TNF inhibitor (n = 6422), IL-6 inhibitor (n = 887), abatacept (n = 1102), or rituximab (n = 1149) in 2017-2019.
- Differences in the change in pain, assessed using a visual analog scale (VAS; 0-100 mm), from baseline to 3 months were compared between the treatment arms.
- The proportion of patients who continued their initial treatment with low pain levels (VAS pain, < 20 mm) at 12 months was also evaluated.
- The comparisons of treatment responses between JAK inhibitors and biologic DMARDs were analyzed using multivariate linear regression, adjusted for patient characteristics, comorbidities, current co-medication, and previous treatment.
TAKEAWAY:
- Pain scores improved from baseline to 3 months in all the treatment arms, with mean changes ranging from −20.1 mm (95% CI, −23.1 to −17.2) for IL-6 inhibitors to −16.6 mm (95% CI, −19.1 to −14.0) for rituximab.
- At 3 months, JAK inhibitors reduced pain scores by 4.0 mm (95% CI, 1.7-6.3) more than TNF inhibitors and by 3.9 mm (95% CI, 0.9-6.9) more than rituximab; however, the change in pain was not significantly different on comparing JAK inhibitors with abatacept or IL-6 inhibitors.
- The superior pain-reducing effects of JAK inhibitors over those of TNF inhibitors were more prominent in those who were previously treated with at least two biologic DMARDs and when the treatments were used as monotherapy.
- At 12 months, 19.5% of the patients receiving JAK inhibitors continued their treatment and achieved low pain levels, with the corresponding proportions ranging from 17% to 26% for biologic DMARDs; JAK inhibitors were more effective in reducing pain than TNF inhibitors, although the difference was not statistically significant.
IN PRACTICE:
“JAK inhibitors yield slightly better pain outcomes than TNF inhibitors. The magnitude of these effects is unlikely to be clinically meaningful in unselected groups of patients with RA,” experts from Feinberg School of Medicine, Northwestern University, Chicago, wrote in an accompanying editorial. “Specific subgroups, such as those who have tried at least two DMARDs, may experience greater effects,” they added.
SOURCE:
The study was led by Anna Eberhard, MD, Department of Clinical Sciences, Lund University, Malmö, Sweden. It was published online on September 22, 2024, in Arthritis & Rheumatology.
LIMITATIONS:
The study had a significant amount of missing data, particularly for follow-up evaluations, which may have introduced bias. The majority of patients were treated using baricitinib, potentially limiting the generalizability to other JAK inhibitors. Residual confounding could not be excluded despite adjustments for multiple relevant patient characteristics.
DISCLOSURES:
This study was supported by grants from The Swedish Research Council, The Swedish Rheumatism Association, and Lund University. Some authors declared receiving consulting fees, payments or honoraria, or grants or having other ties with pharmaceutical companies and other sources.
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:
Janus kinase (JAK) inhibitors had a marginally superior effect on pain relief when compared with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA), particularly when used as monotherapy and in those previously treated with at least two biologic disease-modifying antirheumatic drugs (DMARDs), but their pain reduction effects were similar to those of non–TNF inhibitor biologic DMARDs.
METHODOLOGY:
- Researchers aimed to compare the effect of JAK inhibitors and each class of biologic DMARDs such as TNF inhibitors, rituximab, abatacept, and interleukin (IL)-6 inhibitors on pain in patients with RA in clinical practice.
- They included 8430 patients with RA who were initiated on either a JAK inhibitor (n = 1827), TNF inhibitor (n = 6422), IL-6 inhibitor (n = 887), abatacept (n = 1102), or rituximab (n = 1149) in 2017-2019.
- Differences in the change in pain, assessed using a visual analog scale (VAS; 0-100 mm), from baseline to 3 months were compared between the treatment arms.
- The proportion of patients who continued their initial treatment with low pain levels (VAS pain, < 20 mm) at 12 months was also evaluated.
- The comparisons of treatment responses between JAK inhibitors and biologic DMARDs were analyzed using multivariate linear regression, adjusted for patient characteristics, comorbidities, current co-medication, and previous treatment.
TAKEAWAY:
- Pain scores improved from baseline to 3 months in all the treatment arms, with mean changes ranging from −20.1 mm (95% CI, −23.1 to −17.2) for IL-6 inhibitors to −16.6 mm (95% CI, −19.1 to −14.0) for rituximab.
- At 3 months, JAK inhibitors reduced pain scores by 4.0 mm (95% CI, 1.7-6.3) more than TNF inhibitors and by 3.9 mm (95% CI, 0.9-6.9) more than rituximab; however, the change in pain was not significantly different on comparing JAK inhibitors with abatacept or IL-6 inhibitors.
- The superior pain-reducing effects of JAK inhibitors over those of TNF inhibitors were more prominent in those who were previously treated with at least two biologic DMARDs and when the treatments were used as monotherapy.
- At 12 months, 19.5% of the patients receiving JAK inhibitors continued their treatment and achieved low pain levels, with the corresponding proportions ranging from 17% to 26% for biologic DMARDs; JAK inhibitors were more effective in reducing pain than TNF inhibitors, although the difference was not statistically significant.
IN PRACTICE:
“JAK inhibitors yield slightly better pain outcomes than TNF inhibitors. The magnitude of these effects is unlikely to be clinically meaningful in unselected groups of patients with RA,” experts from Feinberg School of Medicine, Northwestern University, Chicago, wrote in an accompanying editorial. “Specific subgroups, such as those who have tried at least two DMARDs, may experience greater effects,” they added.
SOURCE:
The study was led by Anna Eberhard, MD, Department of Clinical Sciences, Lund University, Malmö, Sweden. It was published online on September 22, 2024, in Arthritis & Rheumatology.
LIMITATIONS:
The study had a significant amount of missing data, particularly for follow-up evaluations, which may have introduced bias. The majority of patients were treated using baricitinib, potentially limiting the generalizability to other JAK inhibitors. Residual confounding could not be excluded despite adjustments for multiple relevant patient characteristics.
DISCLOSURES:
This study was supported by grants from The Swedish Research Council, The Swedish Rheumatism Association, and Lund University. Some authors declared receiving consulting fees, payments or honoraria, or grants or having other ties with pharmaceutical companies and other sources.
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.
Small Bowel Dysmotility Brings Challenges to Patients With Systemic Sclerosis
TOPLINE:
Patients with systemic sclerosis (SSc) who exhibit abnormal small bowel transit are more likely to be men, experience more severe cardiac involvement, have a higher mortality risk, and show fewer sicca symptoms.
METHODOLOGY:
- Researchers enrolled 130 patients with SSc having gastrointestinal (GI) symptoms (mean age at symptom onset, 56.8 years; 90% women; 81% White) seen at the Johns Hopkins Scleroderma Center, Baltimore, from October 2014 to May 2022.
- Clinical data and serum samples were longitudinally collected from all actively followed patients at the time of enrollment and every 6 months thereafter (median disease duration, 8.4 years).
- Participants underwent whole gut transit scintigraphy for the assessment of small bowel motility.
- A cross-sectional analysis compared the clinical features of patients with (n = 22; mean age at symptom onset, 61.4 years) and without (n = 108; mean age at symptom onset, 55.8 years) abnormal small bowel transit.
TAKEAWAY:
- Men with SSc (odds ratio [OR], 3.70; P = .038) and those with severe cardiac involvement (OR, 3.98; P = .035) were more likely to have abnormal small bowel transit.
- Sicca symptoms were negatively associated with abnormal small bowel transit in patients with SSc (adjusted OR, 0.28; P = .043).
- Patients with abnormal small bowel transit reported significantly worse (P = .028) and social functioning (P = .015) than those having a normal transit.
- A multivariate analysis showed that patients with abnormal small bowel transit had higher mortality than those with a normal transit (adjusted hazard ratio, 5.03; P = .005).
IN PRACTICE:
“Our findings improve our understanding of risk factors associated with abnormal small bowel transit in SSc patients and shed light on the lived experience of patients with this GI [gastrointestinal] complication,” the authors wrote. “Overall, these findings are important for patient risk stratification and monitoring and will help to identify a more homogeneous group of patients for future clinical and translational studies,” they added.
SOURCE:
The study was led by Jenice X. Cheah, MD, University of California, Los Angeles. It was published online on October 7, 2024, in Rheumatology.
LIMITATIONS:
The study may be subject to referral bias as it was conducted at a tertiary referral center, potentially including patients with a more severe disease status. Furthermore, this study was retrospective in nature, and whole gut transit studies were not conducted in all the patients seen at the referral center. Additionally, the cross-sectional design limited the ability to establish causality between the clinical features and abnormal small bowel transit.
DISCLOSURES:
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. 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 appeared on Medscape.com.
TOPLINE:
Patients with systemic sclerosis (SSc) who exhibit abnormal small bowel transit are more likely to be men, experience more severe cardiac involvement, have a higher mortality risk, and show fewer sicca symptoms.
METHODOLOGY:
- Researchers enrolled 130 patients with SSc having gastrointestinal (GI) symptoms (mean age at symptom onset, 56.8 years; 90% women; 81% White) seen at the Johns Hopkins Scleroderma Center, Baltimore, from October 2014 to May 2022.
- Clinical data and serum samples were longitudinally collected from all actively followed patients at the time of enrollment and every 6 months thereafter (median disease duration, 8.4 years).
- Participants underwent whole gut transit scintigraphy for the assessment of small bowel motility.
- A cross-sectional analysis compared the clinical features of patients with (n = 22; mean age at symptom onset, 61.4 years) and without (n = 108; mean age at symptom onset, 55.8 years) abnormal small bowel transit.
TAKEAWAY:
- Men with SSc (odds ratio [OR], 3.70; P = .038) and those with severe cardiac involvement (OR, 3.98; P = .035) were more likely to have abnormal small bowel transit.
- Sicca symptoms were negatively associated with abnormal small bowel transit in patients with SSc (adjusted OR, 0.28; P = .043).
- Patients with abnormal small bowel transit reported significantly worse (P = .028) and social functioning (P = .015) than those having a normal transit.
- A multivariate analysis showed that patients with abnormal small bowel transit had higher mortality than those with a normal transit (adjusted hazard ratio, 5.03; P = .005).
IN PRACTICE:
“Our findings improve our understanding of risk factors associated with abnormal small bowel transit in SSc patients and shed light on the lived experience of patients with this GI [gastrointestinal] complication,” the authors wrote. “Overall, these findings are important for patient risk stratification and monitoring and will help to identify a more homogeneous group of patients for future clinical and translational studies,” they added.
SOURCE:
The study was led by Jenice X. Cheah, MD, University of California, Los Angeles. It was published online on October 7, 2024, in Rheumatology.
LIMITATIONS:
The study may be subject to referral bias as it was conducted at a tertiary referral center, potentially including patients with a more severe disease status. Furthermore, this study was retrospective in nature, and whole gut transit studies were not conducted in all the patients seen at the referral center. Additionally, the cross-sectional design limited the ability to establish causality between the clinical features and abnormal small bowel transit.
DISCLOSURES:
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. 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 appeared on Medscape.com.
TOPLINE:
Patients with systemic sclerosis (SSc) who exhibit abnormal small bowel transit are more likely to be men, experience more severe cardiac involvement, have a higher mortality risk, and show fewer sicca symptoms.
METHODOLOGY:
- Researchers enrolled 130 patients with SSc having gastrointestinal (GI) symptoms (mean age at symptom onset, 56.8 years; 90% women; 81% White) seen at the Johns Hopkins Scleroderma Center, Baltimore, from October 2014 to May 2022.
- Clinical data and serum samples were longitudinally collected from all actively followed patients at the time of enrollment and every 6 months thereafter (median disease duration, 8.4 years).
- Participants underwent whole gut transit scintigraphy for the assessment of small bowel motility.
- A cross-sectional analysis compared the clinical features of patients with (n = 22; mean age at symptom onset, 61.4 years) and without (n = 108; mean age at symptom onset, 55.8 years) abnormal small bowel transit.
TAKEAWAY:
- Men with SSc (odds ratio [OR], 3.70; P = .038) and those with severe cardiac involvement (OR, 3.98; P = .035) were more likely to have abnormal small bowel transit.
- Sicca symptoms were negatively associated with abnormal small bowel transit in patients with SSc (adjusted OR, 0.28; P = .043).
- Patients with abnormal small bowel transit reported significantly worse (P = .028) and social functioning (P = .015) than those having a normal transit.
- A multivariate analysis showed that patients with abnormal small bowel transit had higher mortality than those with a normal transit (adjusted hazard ratio, 5.03; P = .005).
IN PRACTICE:
“Our findings improve our understanding of risk factors associated with abnormal small bowel transit in SSc patients and shed light on the lived experience of patients with this GI [gastrointestinal] complication,” the authors wrote. “Overall, these findings are important for patient risk stratification and monitoring and will help to identify a more homogeneous group of patients for future clinical and translational studies,” they added.
SOURCE:
The study was led by Jenice X. Cheah, MD, University of California, Los Angeles. It was published online on October 7, 2024, in Rheumatology.
LIMITATIONS:
The study may be subject to referral bias as it was conducted at a tertiary referral center, potentially including patients with a more severe disease status. Furthermore, this study was retrospective in nature, and whole gut transit studies were not conducted in all the patients seen at the referral center. Additionally, the cross-sectional design limited the ability to establish causality between the clinical features and abnormal small bowel transit.
DISCLOSURES:
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. 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 appeared on Medscape.com.
Gotistobart Trial for NSCLC on Partial Clinical Hold
Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.
“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”
Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
A version of this article appeared on Medscape.com.
Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.
“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”
Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
A version of this article appeared on Medscape.com.
Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.
“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”
Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
A version of this article appeared on Medscape.com.
How Much Does Long COVID Cost Society? New Data Shed Light
Long COVID, a major public health crisis, is also becoming a significant economic crisis. A new study in Nature reports that the global annual economic impact of long COVID has hit $1 trillion — or about 1% of the global economy.
Long COVID is estimated to affect 6%-7% of adults. Those afflicted are often unable to work for extended periods, and some simply stop working altogether.
Besides damaging individual lives, long COVID is having wide-ranging impacts on health systems and economies worldwide, as those who suffer from it have large absences from work, leading to lower productivity. Even those who return to work after weeks, months, or even up to a year out of work may come back with worse productivity and some functional impairment — as a few of the condition’s common symptoms include fatigue and brain fog.
Experts say more is needed not only in terms of scientific research into new treatments for long COVID but also from a public policy perspective.
Long COVID’s impact on the labor force is already having ripple effects throughout the economy of the United States and other countries. Earlier this year, the US Government Accountability Office stated long COVID potentially affects up to 23 million Americans, with as many as a million people out of work. The healthcare industry is particularly hard hit.
The latest survey from the National Center for Health Statistics estimated 17.3%-18.6% of adults have experienced long COVID. This isn’t the same as those who have it now, only a broad indicator of people who’ve ever experienced symptoms.
Public health experts, economists, researchers, and physicians say they are only beginning to focus on ways to reduce long COVID’s impact.
They suggest a range of potential solutions to address the public health crisis and the economic impacts — including implementing a more thorough surveillance system to track long COVID cases, building better ventilation systems in hospitals and buildings to reduce the spread of the virus, increasing vaccination efforts as new viral strains continuously emerge, and more funding for long COVID research to better quantify and qualify the disease’s impact.
Shaky Statistics, Inconsistent Surveillance
David Smith, MD, an infectious disease specialist at the University of California, San Diego, said more needs to be done to survey, quantify, and qualify the impacts of long COVID on the economy before practical solutions can be identified.
“Our surveillance system sucks,” Smith said. “I can see how many people test positive for COVID, but how many of those people have long COVID?”
Long COVID also doesn’t have a true definition or standard diagnosis, which complicates surveillance efforts. It includes a spectrum of symptoms such as shortness of breath, chronic fatigue, and brain fog that linger for 2-3 months after an acute infection. But there’s no “concrete case definition,” Smith said. “And not everybody’s long COVID is exactly the same as everybody else’s.”
As a result, epidemiologists can’t effectively characterize the disease, and health economists can’t measure its exact economic impact.
Few countries have established comprehensive surveillance systems to estimate the burden of long COVID at the population level.
The United States currently tracks new cases by measuring wastewater levels, which isn’t as comprehensive as the tracking that was done during the pandemic. But positive wastewater samples can’t tell us who is infected in an area, nor can it distinguish whether a visitor/tourist or resident is mostly contributing to the wastewater analysis — an important distinction in public health studies.
Wastewater surveillance is an excellent complement to traditional disease surveillance with advantages and disadvantages, but it shouldn’t be the sole way to measure disease.
What Research Best Informs the Debate?
A study by Economist Impact — a think tank that partners with corporations, foundations, NGOs, and governments to help drive policy — estimated between a 0.5% and 2.3% gross domestic product (GDP) loss across eight separate countries in 2024. The study included the United Kingdom and United States.
Meanwhile, Australian researchers recently detailed how long COVID-related reductions in labor supply affected its productivity and GDP from 2022 to 2024. The study found that long COVID could be costing the Australian economy about 0.5% of its GDP, which researchers deemed a conservative estimate.
Public health researchers in New Zealand used the estimate of GDP loss in Australia to measure their own potential losses and advocated for strengthening occupational support across all sectors to protect health.
But these studies can’t quite compare with what would have to be done for the United States economy.
“New Zealand is small ... and has an excellent public health system with good delivery of vaccines and treatments…so how do we compare that to us?” Smith said. “They do better in all of their public health metrics than we do.”
Measuring the Economic Impact
Gopi Shah Goda, PhD, a health economist and senior fellow in economic studies at the Brookings Institution, co-authored a 2023 study that found COVID-19 reduced the US labor force by about 500,000 people.
Plus, workers who missed a full week due to COVID-19 absences became 7% less likely to return to the labor force a year later compared with workers who didn’t miss work for health reasons. That amounts to 0.2% of the labor force, a significant number.
“Even a small percent of the labor force is a big number…it’s like an extra year of populating aging,” Goda said.
“Some people who get long COVID might have dropped out of the labor force anyway,” Goda added.
The study concluded that average individual earnings lost from long COVID were $9000, and the total lost labor supply amounted to $62 billion annually — about half the estimated productivity losses from cancer or diabetes.
But research into long COVID research continues to be underfunded compared with other health conditions, experts noted.
Cancer and diabetes both receive billions of research dollars annually from the National Institutes of Health. Long COVID research gets only a few million, according to Goda.
Informing Public Health Policy
When it comes to caring for patients with long COVID, the big issue facing every nation’s public policy leaders is how best to allocate limited health resources.
“Public health never has enough money ... Do they buy more vaccines? Do they do educational programs? Who do they target the most?” Smith said.
Though Smith thinks the best preventative measure is increased vaccination, vaccination rates remain low in the United States.
“Unfortunately, as last fall demonstrated, there’s a lot of vaccine indifference and skepticism,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University School of Medicine, Nashville, Tennessee.
Over the past year, only 14% of eligible children and 22% of adults received the 2023-2024 COVID vaccine boosters.
Schaffner said public health experts wrestle with ways to assure the public vaccines are safe and effective.
“They’re trying to provide a level of comfort that [getting vaccinated] is the socially appropriate thing to do,” which remains a significant challenge, Schaffner said.
Some people don’t have access to vaccines and comprehensive medical services because they lack insurance, Medicaid, and Medicare. And the United States still doesn’t distribute vaccines as well as other countries, Schaffner added.
“In other countries, every doctor’s office gets vaccines for free ... here, we have a large commercial enterprise that basically runs it…there are still populations who aren’t reached,” he said.
Long COVID clinics that have opened around the country have offered help to some patients with long COVID. A year and a half ago, Yale University, New Haven, Connecticut, established its Long COVID Care Center. Stanford University, Stanford, California, opened its Long COVID Clinic back in 2021. Vanderbilt University now has its own, as well — the Adult Post-COVID Clinic.
But these clinics have faced declining federal resources, forcing some to close and others to face questions about whether they will be able to continue to operate without more aggressive federal direction and policy planning.
“With some central direction, we could provide better supportive care for the many patients with long COVID out there,” Schaffner said.
For countries with universal healthcare systems, services such as occupational health, extended sick leave, extended time for disability, and workers’ compensation benefits are readily available.
But in the United States, it’s often left to the physicians and their patients to figure out a plan.
“I think we could make physicians more aware of options for their patients…for example, regularly check eligibility for workers compensation,” Schaffner said.
A version of this article first appeared on Medscape.com.
Long COVID, a major public health crisis, is also becoming a significant economic crisis. A new study in Nature reports that the global annual economic impact of long COVID has hit $1 trillion — or about 1% of the global economy.
Long COVID is estimated to affect 6%-7% of adults. Those afflicted are often unable to work for extended periods, and some simply stop working altogether.
Besides damaging individual lives, long COVID is having wide-ranging impacts on health systems and economies worldwide, as those who suffer from it have large absences from work, leading to lower productivity. Even those who return to work after weeks, months, or even up to a year out of work may come back with worse productivity and some functional impairment — as a few of the condition’s common symptoms include fatigue and brain fog.
Experts say more is needed not only in terms of scientific research into new treatments for long COVID but also from a public policy perspective.
Long COVID’s impact on the labor force is already having ripple effects throughout the economy of the United States and other countries. Earlier this year, the US Government Accountability Office stated long COVID potentially affects up to 23 million Americans, with as many as a million people out of work. The healthcare industry is particularly hard hit.
The latest survey from the National Center for Health Statistics estimated 17.3%-18.6% of adults have experienced long COVID. This isn’t the same as those who have it now, only a broad indicator of people who’ve ever experienced symptoms.
Public health experts, economists, researchers, and physicians say they are only beginning to focus on ways to reduce long COVID’s impact.
They suggest a range of potential solutions to address the public health crisis and the economic impacts — including implementing a more thorough surveillance system to track long COVID cases, building better ventilation systems in hospitals and buildings to reduce the spread of the virus, increasing vaccination efforts as new viral strains continuously emerge, and more funding for long COVID research to better quantify and qualify the disease’s impact.
Shaky Statistics, Inconsistent Surveillance
David Smith, MD, an infectious disease specialist at the University of California, San Diego, said more needs to be done to survey, quantify, and qualify the impacts of long COVID on the economy before practical solutions can be identified.
“Our surveillance system sucks,” Smith said. “I can see how many people test positive for COVID, but how many of those people have long COVID?”
Long COVID also doesn’t have a true definition or standard diagnosis, which complicates surveillance efforts. It includes a spectrum of symptoms such as shortness of breath, chronic fatigue, and brain fog that linger for 2-3 months after an acute infection. But there’s no “concrete case definition,” Smith said. “And not everybody’s long COVID is exactly the same as everybody else’s.”
As a result, epidemiologists can’t effectively characterize the disease, and health economists can’t measure its exact economic impact.
Few countries have established comprehensive surveillance systems to estimate the burden of long COVID at the population level.
The United States currently tracks new cases by measuring wastewater levels, which isn’t as comprehensive as the tracking that was done during the pandemic. But positive wastewater samples can’t tell us who is infected in an area, nor can it distinguish whether a visitor/tourist or resident is mostly contributing to the wastewater analysis — an important distinction in public health studies.
Wastewater surveillance is an excellent complement to traditional disease surveillance with advantages and disadvantages, but it shouldn’t be the sole way to measure disease.
What Research Best Informs the Debate?
A study by Economist Impact — a think tank that partners with corporations, foundations, NGOs, and governments to help drive policy — estimated between a 0.5% and 2.3% gross domestic product (GDP) loss across eight separate countries in 2024. The study included the United Kingdom and United States.
Meanwhile, Australian researchers recently detailed how long COVID-related reductions in labor supply affected its productivity and GDP from 2022 to 2024. The study found that long COVID could be costing the Australian economy about 0.5% of its GDP, which researchers deemed a conservative estimate.
Public health researchers in New Zealand used the estimate of GDP loss in Australia to measure their own potential losses and advocated for strengthening occupational support across all sectors to protect health.
But these studies can’t quite compare with what would have to be done for the United States economy.
“New Zealand is small ... and has an excellent public health system with good delivery of vaccines and treatments…so how do we compare that to us?” Smith said. “They do better in all of their public health metrics than we do.”
Measuring the Economic Impact
Gopi Shah Goda, PhD, a health economist and senior fellow in economic studies at the Brookings Institution, co-authored a 2023 study that found COVID-19 reduced the US labor force by about 500,000 people.
Plus, workers who missed a full week due to COVID-19 absences became 7% less likely to return to the labor force a year later compared with workers who didn’t miss work for health reasons. That amounts to 0.2% of the labor force, a significant number.
“Even a small percent of the labor force is a big number…it’s like an extra year of populating aging,” Goda said.
“Some people who get long COVID might have dropped out of the labor force anyway,” Goda added.
The study concluded that average individual earnings lost from long COVID were $9000, and the total lost labor supply amounted to $62 billion annually — about half the estimated productivity losses from cancer or diabetes.
But research into long COVID research continues to be underfunded compared with other health conditions, experts noted.
Cancer and diabetes both receive billions of research dollars annually from the National Institutes of Health. Long COVID research gets only a few million, according to Goda.
Informing Public Health Policy
When it comes to caring for patients with long COVID, the big issue facing every nation’s public policy leaders is how best to allocate limited health resources.
“Public health never has enough money ... Do they buy more vaccines? Do they do educational programs? Who do they target the most?” Smith said.
Though Smith thinks the best preventative measure is increased vaccination, vaccination rates remain low in the United States.
“Unfortunately, as last fall demonstrated, there’s a lot of vaccine indifference and skepticism,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University School of Medicine, Nashville, Tennessee.
Over the past year, only 14% of eligible children and 22% of adults received the 2023-2024 COVID vaccine boosters.
Schaffner said public health experts wrestle with ways to assure the public vaccines are safe and effective.
“They’re trying to provide a level of comfort that [getting vaccinated] is the socially appropriate thing to do,” which remains a significant challenge, Schaffner said.
Some people don’t have access to vaccines and comprehensive medical services because they lack insurance, Medicaid, and Medicare. And the United States still doesn’t distribute vaccines as well as other countries, Schaffner added.
“In other countries, every doctor’s office gets vaccines for free ... here, we have a large commercial enterprise that basically runs it…there are still populations who aren’t reached,” he said.
Long COVID clinics that have opened around the country have offered help to some patients with long COVID. A year and a half ago, Yale University, New Haven, Connecticut, established its Long COVID Care Center. Stanford University, Stanford, California, opened its Long COVID Clinic back in 2021. Vanderbilt University now has its own, as well — the Adult Post-COVID Clinic.
But these clinics have faced declining federal resources, forcing some to close and others to face questions about whether they will be able to continue to operate without more aggressive federal direction and policy planning.
“With some central direction, we could provide better supportive care for the many patients with long COVID out there,” Schaffner said.
For countries with universal healthcare systems, services such as occupational health, extended sick leave, extended time for disability, and workers’ compensation benefits are readily available.
But in the United States, it’s often left to the physicians and their patients to figure out a plan.
“I think we could make physicians more aware of options for their patients…for example, regularly check eligibility for workers compensation,” Schaffner said.
A version of this article first appeared on Medscape.com.
Long COVID, a major public health crisis, is also becoming a significant economic crisis. A new study in Nature reports that the global annual economic impact of long COVID has hit $1 trillion — or about 1% of the global economy.
Long COVID is estimated to affect 6%-7% of adults. Those afflicted are often unable to work for extended periods, and some simply stop working altogether.
Besides damaging individual lives, long COVID is having wide-ranging impacts on health systems and economies worldwide, as those who suffer from it have large absences from work, leading to lower productivity. Even those who return to work after weeks, months, or even up to a year out of work may come back with worse productivity and some functional impairment — as a few of the condition’s common symptoms include fatigue and brain fog.
Experts say more is needed not only in terms of scientific research into new treatments for long COVID but also from a public policy perspective.
Long COVID’s impact on the labor force is already having ripple effects throughout the economy of the United States and other countries. Earlier this year, the US Government Accountability Office stated long COVID potentially affects up to 23 million Americans, with as many as a million people out of work. The healthcare industry is particularly hard hit.
The latest survey from the National Center for Health Statistics estimated 17.3%-18.6% of adults have experienced long COVID. This isn’t the same as those who have it now, only a broad indicator of people who’ve ever experienced symptoms.
Public health experts, economists, researchers, and physicians say they are only beginning to focus on ways to reduce long COVID’s impact.
They suggest a range of potential solutions to address the public health crisis and the economic impacts — including implementing a more thorough surveillance system to track long COVID cases, building better ventilation systems in hospitals and buildings to reduce the spread of the virus, increasing vaccination efforts as new viral strains continuously emerge, and more funding for long COVID research to better quantify and qualify the disease’s impact.
Shaky Statistics, Inconsistent Surveillance
David Smith, MD, an infectious disease specialist at the University of California, San Diego, said more needs to be done to survey, quantify, and qualify the impacts of long COVID on the economy before practical solutions can be identified.
“Our surveillance system sucks,” Smith said. “I can see how many people test positive for COVID, but how many of those people have long COVID?”
Long COVID also doesn’t have a true definition or standard diagnosis, which complicates surveillance efforts. It includes a spectrum of symptoms such as shortness of breath, chronic fatigue, and brain fog that linger for 2-3 months after an acute infection. But there’s no “concrete case definition,” Smith said. “And not everybody’s long COVID is exactly the same as everybody else’s.”
As a result, epidemiologists can’t effectively characterize the disease, and health economists can’t measure its exact economic impact.
Few countries have established comprehensive surveillance systems to estimate the burden of long COVID at the population level.
The United States currently tracks new cases by measuring wastewater levels, which isn’t as comprehensive as the tracking that was done during the pandemic. But positive wastewater samples can’t tell us who is infected in an area, nor can it distinguish whether a visitor/tourist or resident is mostly contributing to the wastewater analysis — an important distinction in public health studies.
Wastewater surveillance is an excellent complement to traditional disease surveillance with advantages and disadvantages, but it shouldn’t be the sole way to measure disease.
What Research Best Informs the Debate?
A study by Economist Impact — a think tank that partners with corporations, foundations, NGOs, and governments to help drive policy — estimated between a 0.5% and 2.3% gross domestic product (GDP) loss across eight separate countries in 2024. The study included the United Kingdom and United States.
Meanwhile, Australian researchers recently detailed how long COVID-related reductions in labor supply affected its productivity and GDP from 2022 to 2024. The study found that long COVID could be costing the Australian economy about 0.5% of its GDP, which researchers deemed a conservative estimate.
Public health researchers in New Zealand used the estimate of GDP loss in Australia to measure their own potential losses and advocated for strengthening occupational support across all sectors to protect health.
But these studies can’t quite compare with what would have to be done for the United States economy.
“New Zealand is small ... and has an excellent public health system with good delivery of vaccines and treatments…so how do we compare that to us?” Smith said. “They do better in all of their public health metrics than we do.”
Measuring the Economic Impact
Gopi Shah Goda, PhD, a health economist and senior fellow in economic studies at the Brookings Institution, co-authored a 2023 study that found COVID-19 reduced the US labor force by about 500,000 people.
Plus, workers who missed a full week due to COVID-19 absences became 7% less likely to return to the labor force a year later compared with workers who didn’t miss work for health reasons. That amounts to 0.2% of the labor force, a significant number.
“Even a small percent of the labor force is a big number…it’s like an extra year of populating aging,” Goda said.
“Some people who get long COVID might have dropped out of the labor force anyway,” Goda added.
The study concluded that average individual earnings lost from long COVID were $9000, and the total lost labor supply amounted to $62 billion annually — about half the estimated productivity losses from cancer or diabetes.
But research into long COVID research continues to be underfunded compared with other health conditions, experts noted.
Cancer and diabetes both receive billions of research dollars annually from the National Institutes of Health. Long COVID research gets only a few million, according to Goda.
Informing Public Health Policy
When it comes to caring for patients with long COVID, the big issue facing every nation’s public policy leaders is how best to allocate limited health resources.
“Public health never has enough money ... Do they buy more vaccines? Do they do educational programs? Who do they target the most?” Smith said.
Though Smith thinks the best preventative measure is increased vaccination, vaccination rates remain low in the United States.
“Unfortunately, as last fall demonstrated, there’s a lot of vaccine indifference and skepticism,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University School of Medicine, Nashville, Tennessee.
Over the past year, only 14% of eligible children and 22% of adults received the 2023-2024 COVID vaccine boosters.
Schaffner said public health experts wrestle with ways to assure the public vaccines are safe and effective.
“They’re trying to provide a level of comfort that [getting vaccinated] is the socially appropriate thing to do,” which remains a significant challenge, Schaffner said.
Some people don’t have access to vaccines and comprehensive medical services because they lack insurance, Medicaid, and Medicare. And the United States still doesn’t distribute vaccines as well as other countries, Schaffner added.
“In other countries, every doctor’s office gets vaccines for free ... here, we have a large commercial enterprise that basically runs it…there are still populations who aren’t reached,” he said.
Long COVID clinics that have opened around the country have offered help to some patients with long COVID. A year and a half ago, Yale University, New Haven, Connecticut, established its Long COVID Care Center. Stanford University, Stanford, California, opened its Long COVID Clinic back in 2021. Vanderbilt University now has its own, as well — the Adult Post-COVID Clinic.
But these clinics have faced declining federal resources, forcing some to close and others to face questions about whether they will be able to continue to operate without more aggressive federal direction and policy planning.
“With some central direction, we could provide better supportive care for the many patients with long COVID out there,” Schaffner said.
For countries with universal healthcare systems, services such as occupational health, extended sick leave, extended time for disability, and workers’ compensation benefits are readily available.
But in the United States, it’s often left to the physicians and their patients to figure out a plan.
“I think we could make physicians more aware of options for their patients…for example, regularly check eligibility for workers compensation,” Schaffner said.
A version of this article first appeared on Medscape.com.
FROM NATURE
Groups With Highest Unmet Need for PrEP Highlighted in Analysis
LOS ANGELES — Use of preexposure prophylaxis (PrEP) to prevent HIV is increasing overall, but both the rate of increase for starting PrEP and the rate of unmet need differ widely by demographic group, according to new data from a large study.
An analysis by Li Tao, MD, MS, PhD, director of real-world evidence at Gilead Sciences, and colleagues looked at statistical trends from 2019 to 2023 and found that Black, Hispanic, and Medicaid-insured populations continue to lack equitable access to PrEP.
Among the findings were that most new PrEP users were men with HIV risk factors who are commercially insured and live in predominantly non-Hispanic White areas (53% in 2019 and 43% in 2023). For comparison, men living in predominantly Black or Hispanic neighborhoods, or who are insured by Medicaid, saw lower proportions of PrEP use (16% in 2019 and 17% in 2023) despite higher annual increases in PrEP use (11% per year) and higher unmet needs.
Half a Million Real-World Participants
Tao presented her team’s findings at the Infectious Disease Week (IDWeek) 2024 Annual Meeting. The study included “more than half a million real-world PrEP users over the past 5 years,” she said.
The group with the lowest growth in initiation of PrEP in the study period (an annual percentage increase of 2%) and the lowest unmet need included men with HIV risk factors, who were using commercial insurance and living in White-dominant neighborhoods.
HIV risk factors included diagnosis of any sexually transmitted disease, contact with and exposure to communicable diseases, high-risk sexual behavior, contact with a hypodermic needle, long-term prophylaxis, HIV prevention counseling, and HIV screening.
Other men with HIV risk factors (those who were commercially insured, living in Black/Hispanic neighborhoods, or those on Medicaid across all neighborhoods) had a moderate increase in PrEP initiation (an annual percentage increase of 11%-16%) and higher unmet needs.
Researchers gathered data on PrEP prescriptions and new HIV diagnoses (from 2019 to 2023) through the IQVIA pharmacy claims database. PrEP-to-need ratio (PNR) is the number of individuals using PrEP in a year divided by new HIV diagnoses in the previous year. It was calculated for subgroups defined by five PNR-associated factors: Sex, insurance, recorded HIV risk factors (identified by diagnosis or procedure codes), “Ending the HIV Epidemic” jurisdictions, and neighborhood race/ethnicity mix.
Disparities Persist
While PrEP use improved across all the groups studied in the 5 years, “disparities still persist and the need remains very significant,” Tao said. “It’s very crucial for guiding the future HIV prevention options.”
“Long-acting PrEP options may help to address some social determinants structural factors in HIV acquisition,” she added.
What Programs Are Helping?
Some guidelines and programs are helping increase uptake, Tao said.
The United States Preventive Services Task Force (USPSTF) guidelines “reinforce more accessible PrEP programs to individuals like zero-cost sharing or same-day dispensing,” Tao said in a press briefing. “Those kinds of policies are really effective. We can see that after the implementation of the USPSTF guidelines, the copay sharing is really decreasing and is coinciding with the HIV rates declining.”
The Medicaid coverage expansion in 40 states “has been really effective” in PrEP uptake, she added.
Colleen Kelley, MD, MPH, with the Division of Infectious Diseases at the Rollins School of Public Health, Emory University, in Atlanta, who was not part of the research, said there has been a slow but improving uptake of PrEP across the board in the United States, “but the issue is that the uptake has been inequitable.”
Large Study With Recent Data
“This is an extremely large study with very recent data,” Kelley said. “Additionally, they were able to couple (the uptake) with unmet need. People who are at higher risk of acquiring HIV or who live in high-risk areas for HIV should have greater access to PrEP. They have a greater need for PrEP. What we really need to do from an equity perspective is match the PrEP use with the PrEP need and we have not been successful in doing that.”
Kelley added that the finding that the group that had the highest unmet need for PrEP in the study also had no recorded HIV risk factors. “It’s an interesting time to start thinking about beyond risk factor coverage for PrEP,” she said.
Another issue, Kelley said, is that “people are using (PrEP) but they’re also stopping it. People will need to take PrEP many years for protection, but about half discontinue in the first 6-12 months.
“We need to look at how people will persist on PrEP over the long term. That’s the next frontier,” she said. “We hope the long-acting injectables will help overcome some of the PrEP fatigue. But some may just tire of taking medication repeatedly for an infection they don’t have,” she said.
The study was funded by Gilead Sciences. Tao is employed by and is a shareholder of Gilead Sciences. All relevant financial disclosures have been mitigated, according to the paper. Kelley has research grants to her institution from Gilead, Moderna, Novavax, ViiV, and Humanigen.
A version of this article first appeared on Medscape.com.
LOS ANGELES — Use of preexposure prophylaxis (PrEP) to prevent HIV is increasing overall, but both the rate of increase for starting PrEP and the rate of unmet need differ widely by demographic group, according to new data from a large study.
An analysis by Li Tao, MD, MS, PhD, director of real-world evidence at Gilead Sciences, and colleagues looked at statistical trends from 2019 to 2023 and found that Black, Hispanic, and Medicaid-insured populations continue to lack equitable access to PrEP.
Among the findings were that most new PrEP users were men with HIV risk factors who are commercially insured and live in predominantly non-Hispanic White areas (53% in 2019 and 43% in 2023). For comparison, men living in predominantly Black or Hispanic neighborhoods, or who are insured by Medicaid, saw lower proportions of PrEP use (16% in 2019 and 17% in 2023) despite higher annual increases in PrEP use (11% per year) and higher unmet needs.
Half a Million Real-World Participants
Tao presented her team’s findings at the Infectious Disease Week (IDWeek) 2024 Annual Meeting. The study included “more than half a million real-world PrEP users over the past 5 years,” she said.
The group with the lowest growth in initiation of PrEP in the study period (an annual percentage increase of 2%) and the lowest unmet need included men with HIV risk factors, who were using commercial insurance and living in White-dominant neighborhoods.
HIV risk factors included diagnosis of any sexually transmitted disease, contact with and exposure to communicable diseases, high-risk sexual behavior, contact with a hypodermic needle, long-term prophylaxis, HIV prevention counseling, and HIV screening.
Other men with HIV risk factors (those who were commercially insured, living in Black/Hispanic neighborhoods, or those on Medicaid across all neighborhoods) had a moderate increase in PrEP initiation (an annual percentage increase of 11%-16%) and higher unmet needs.
Researchers gathered data on PrEP prescriptions and new HIV diagnoses (from 2019 to 2023) through the IQVIA pharmacy claims database. PrEP-to-need ratio (PNR) is the number of individuals using PrEP in a year divided by new HIV diagnoses in the previous year. It was calculated for subgroups defined by five PNR-associated factors: Sex, insurance, recorded HIV risk factors (identified by diagnosis or procedure codes), “Ending the HIV Epidemic” jurisdictions, and neighborhood race/ethnicity mix.
Disparities Persist
While PrEP use improved across all the groups studied in the 5 years, “disparities still persist and the need remains very significant,” Tao said. “It’s very crucial for guiding the future HIV prevention options.”
“Long-acting PrEP options may help to address some social determinants structural factors in HIV acquisition,” she added.
What Programs Are Helping?
Some guidelines and programs are helping increase uptake, Tao said.
The United States Preventive Services Task Force (USPSTF) guidelines “reinforce more accessible PrEP programs to individuals like zero-cost sharing or same-day dispensing,” Tao said in a press briefing. “Those kinds of policies are really effective. We can see that after the implementation of the USPSTF guidelines, the copay sharing is really decreasing and is coinciding with the HIV rates declining.”
The Medicaid coverage expansion in 40 states “has been really effective” in PrEP uptake, she added.
Colleen Kelley, MD, MPH, with the Division of Infectious Diseases at the Rollins School of Public Health, Emory University, in Atlanta, who was not part of the research, said there has been a slow but improving uptake of PrEP across the board in the United States, “but the issue is that the uptake has been inequitable.”
Large Study With Recent Data
“This is an extremely large study with very recent data,” Kelley said. “Additionally, they were able to couple (the uptake) with unmet need. People who are at higher risk of acquiring HIV or who live in high-risk areas for HIV should have greater access to PrEP. They have a greater need for PrEP. What we really need to do from an equity perspective is match the PrEP use with the PrEP need and we have not been successful in doing that.”
Kelley added that the finding that the group that had the highest unmet need for PrEP in the study also had no recorded HIV risk factors. “It’s an interesting time to start thinking about beyond risk factor coverage for PrEP,” she said.
Another issue, Kelley said, is that “people are using (PrEP) but they’re also stopping it. People will need to take PrEP many years for protection, but about half discontinue in the first 6-12 months.
“We need to look at how people will persist on PrEP over the long term. That’s the next frontier,” she said. “We hope the long-acting injectables will help overcome some of the PrEP fatigue. But some may just tire of taking medication repeatedly for an infection they don’t have,” she said.
The study was funded by Gilead Sciences. Tao is employed by and is a shareholder of Gilead Sciences. All relevant financial disclosures have been mitigated, according to the paper. Kelley has research grants to her institution from Gilead, Moderna, Novavax, ViiV, and Humanigen.
A version of this article first appeared on Medscape.com.
LOS ANGELES — Use of preexposure prophylaxis (PrEP) to prevent HIV is increasing overall, but both the rate of increase for starting PrEP and the rate of unmet need differ widely by demographic group, according to new data from a large study.
An analysis by Li Tao, MD, MS, PhD, director of real-world evidence at Gilead Sciences, and colleagues looked at statistical trends from 2019 to 2023 and found that Black, Hispanic, and Medicaid-insured populations continue to lack equitable access to PrEP.
Among the findings were that most new PrEP users were men with HIV risk factors who are commercially insured and live in predominantly non-Hispanic White areas (53% in 2019 and 43% in 2023). For comparison, men living in predominantly Black or Hispanic neighborhoods, or who are insured by Medicaid, saw lower proportions of PrEP use (16% in 2019 and 17% in 2023) despite higher annual increases in PrEP use (11% per year) and higher unmet needs.
Half a Million Real-World Participants
Tao presented her team’s findings at the Infectious Disease Week (IDWeek) 2024 Annual Meeting. The study included “more than half a million real-world PrEP users over the past 5 years,” she said.
The group with the lowest growth in initiation of PrEP in the study period (an annual percentage increase of 2%) and the lowest unmet need included men with HIV risk factors, who were using commercial insurance and living in White-dominant neighborhoods.
HIV risk factors included diagnosis of any sexually transmitted disease, contact with and exposure to communicable diseases, high-risk sexual behavior, contact with a hypodermic needle, long-term prophylaxis, HIV prevention counseling, and HIV screening.
Other men with HIV risk factors (those who were commercially insured, living in Black/Hispanic neighborhoods, or those on Medicaid across all neighborhoods) had a moderate increase in PrEP initiation (an annual percentage increase of 11%-16%) and higher unmet needs.
Researchers gathered data on PrEP prescriptions and new HIV diagnoses (from 2019 to 2023) through the IQVIA pharmacy claims database. PrEP-to-need ratio (PNR) is the number of individuals using PrEP in a year divided by new HIV diagnoses in the previous year. It was calculated for subgroups defined by five PNR-associated factors: Sex, insurance, recorded HIV risk factors (identified by diagnosis or procedure codes), “Ending the HIV Epidemic” jurisdictions, and neighborhood race/ethnicity mix.
Disparities Persist
While PrEP use improved across all the groups studied in the 5 years, “disparities still persist and the need remains very significant,” Tao said. “It’s very crucial for guiding the future HIV prevention options.”
“Long-acting PrEP options may help to address some social determinants structural factors in HIV acquisition,” she added.
What Programs Are Helping?
Some guidelines and programs are helping increase uptake, Tao said.
The United States Preventive Services Task Force (USPSTF) guidelines “reinforce more accessible PrEP programs to individuals like zero-cost sharing or same-day dispensing,” Tao said in a press briefing. “Those kinds of policies are really effective. We can see that after the implementation of the USPSTF guidelines, the copay sharing is really decreasing and is coinciding with the HIV rates declining.”
The Medicaid coverage expansion in 40 states “has been really effective” in PrEP uptake, she added.
Colleen Kelley, MD, MPH, with the Division of Infectious Diseases at the Rollins School of Public Health, Emory University, in Atlanta, who was not part of the research, said there has been a slow but improving uptake of PrEP across the board in the United States, “but the issue is that the uptake has been inequitable.”
Large Study With Recent Data
“This is an extremely large study with very recent data,” Kelley said. “Additionally, they were able to couple (the uptake) with unmet need. People who are at higher risk of acquiring HIV or who live in high-risk areas for HIV should have greater access to PrEP. They have a greater need for PrEP. What we really need to do from an equity perspective is match the PrEP use with the PrEP need and we have not been successful in doing that.”
Kelley added that the finding that the group that had the highest unmet need for PrEP in the study also had no recorded HIV risk factors. “It’s an interesting time to start thinking about beyond risk factor coverage for PrEP,” she said.
Another issue, Kelley said, is that “people are using (PrEP) but they’re also stopping it. People will need to take PrEP many years for protection, but about half discontinue in the first 6-12 months.
“We need to look at how people will persist on PrEP over the long term. That’s the next frontier,” she said. “We hope the long-acting injectables will help overcome some of the PrEP fatigue. But some may just tire of taking medication repeatedly for an infection they don’t have,” she said.
The study was funded by Gilead Sciences. Tao is employed by and is a shareholder of Gilead Sciences. All relevant financial disclosures have been mitigated, according to the paper. Kelley has research grants to her institution from Gilead, Moderna, Novavax, ViiV, and Humanigen.
A version of this article first appeared on Medscape.com.
FROM IDWEEK 2024
Pediatric Myasthenia Gravis: Don’t Treat Children Like Adults
SAVANNAH, GEORGIA — At a pathophysiological level, juvenile myasthenia gravis (MG) seems to be identical to the adult form, neuromuscular specialists learned. But there are still important differences between children and their elders that affect pediatric care.
For example, “we have to think a little bit differently about the side effect profiles of the medications and their toxicity because children may react to medications differently,” said Matthew Ginsberg, MD, a pediatric neurologist based in Akron, Ohio, in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
And then there’s the matter of adherence. “It’s hard to get adults to take medication, but a teenager is sometimes an exceptional challenge,” Ginsberg said.
Case In Point: A 13-Year-Old With MG
Pediatric MG is rare. Cases in children are estimated to account for 10% of MG cases diagnosed each year. According to a 2020 report, “the majority will present with ptosis and a variable degree of ophthalmoplegia [paralysis of eye muscles].”
Ginsberg highlighted a case of a 13-year-old girl who’d been healthy but developed fatigable ptosis and mild restriction of extraocular movements. The patient’s acetylcholine receptor antibodies were very elevated, but she didn’t have MuSK antibodies.
“This isn’t a diagnostic conundrum. She has autoimmune myasthenia gravis with ocular manifestations,” Ginsberg said. “For someone like this, whether it’s an adult or a child, many people would start symptomatic treatment with an acetylcholinesterase inhibitor like pyridostigmine.”
The use of the drug in children is similar to that in adults, he said, although weight-based dosing is used. “Usually it’s around 3-7 mg/kg/d, but it’s still very individualized based on patient response.” The timing of symptoms can affect the distribution of doses throughout the day, he said.
“There are extended-release formulations of the medication, and I think some people use them more than I do,” he said. “The side effects are basically similar to adults. Most of the patients I have on it tolerate it really well and don’t have a lot of the muscarinic side effects that you would expect.”
Consider Prescription Eye Drops for Ptosis
Alpha-1A agonists oxymetazoline and apraclonidine in the form of topical eye drops can help with ptosis. “They potentially avoid some of the systemic toxicity of the other medications,” Ginsberg said. “So they might be an option if you’re really just trying to target ptosis as a symptom.”
However, it can be difficult to get insurers to cover these medications, he said.
The 13-year-old patient initially improved but developed difficulty walking. “Her hands began to feel heavy, and she had difficulty chewing and nasal regurgitation. On her exam, she still had fatigable ptosis plus hypernasal speech and generalized weakness. At this point, we’re starting to see that she has generalized myasthenia gravis that may be an impending crisis.”
The Young Patient Worsens. Now What?
The patient was admitted and given intravenous immunoglobulin at 2 g/kg over a couple days. But her symptoms worsened following initial improvement.
Glucocorticoids can play a larger role in treatment at this stage, and the patient was initially on prednisone. But there are reasons for caution, including effects on bone growth and interference with live vaccines.
However, live vaccines aren’t common in children, with the exception of the MMRV vaccine, he said. “It’s worth noting that you can give that second dose as early as 3 months after the initial one, so most patients really should be able to complete a course before they start on immunosuppression,” he said.
Another option is immunotherapy. “There’s a really large menu of options for immunotherapy in myasthenia gravis right now,” Ginsberg said. “It’s great that we have all these options, but it adds to the complexity.”
Rituximab may be considered based on early data, he said. And thymectomy — removal of the thymus gland — should be considered early.
Don’t Neglect Supportive Care
Ginsberg urged colleagues to consider supportive care measures. Advocacy groups such as the Myasthenia Gravis Foundation of America can help with weight management and diet/exercise counseling, especially in patients taking glucocorticoids.
He added that “school accommodations are very important in this age group. They might need a plan, for example, to have modified gym class or an excuse not to carry a book bag between classes.”
How did the 13-year-old do? She underwent thymectomy, and her disease remained stable after 6 months. “Her rituximab was discontinued,” Ginsberg said. “She considered participating in a clinical trial but then started seeing improvements. About a year after the thymectomy, she just stopped her steroids on her own, and she was fine.”
Ginsberg had no disclosures.
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA — At a pathophysiological level, juvenile myasthenia gravis (MG) seems to be identical to the adult form, neuromuscular specialists learned. But there are still important differences between children and their elders that affect pediatric care.
For example, “we have to think a little bit differently about the side effect profiles of the medications and their toxicity because children may react to medications differently,” said Matthew Ginsberg, MD, a pediatric neurologist based in Akron, Ohio, in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
And then there’s the matter of adherence. “It’s hard to get adults to take medication, but a teenager is sometimes an exceptional challenge,” Ginsberg said.
Case In Point: A 13-Year-Old With MG
Pediatric MG is rare. Cases in children are estimated to account for 10% of MG cases diagnosed each year. According to a 2020 report, “the majority will present with ptosis and a variable degree of ophthalmoplegia [paralysis of eye muscles].”
Ginsberg highlighted a case of a 13-year-old girl who’d been healthy but developed fatigable ptosis and mild restriction of extraocular movements. The patient’s acetylcholine receptor antibodies were very elevated, but she didn’t have MuSK antibodies.
“This isn’t a diagnostic conundrum. She has autoimmune myasthenia gravis with ocular manifestations,” Ginsberg said. “For someone like this, whether it’s an adult or a child, many people would start symptomatic treatment with an acetylcholinesterase inhibitor like pyridostigmine.”
The use of the drug in children is similar to that in adults, he said, although weight-based dosing is used. “Usually it’s around 3-7 mg/kg/d, but it’s still very individualized based on patient response.” The timing of symptoms can affect the distribution of doses throughout the day, he said.
“There are extended-release formulations of the medication, and I think some people use them more than I do,” he said. “The side effects are basically similar to adults. Most of the patients I have on it tolerate it really well and don’t have a lot of the muscarinic side effects that you would expect.”
Consider Prescription Eye Drops for Ptosis
Alpha-1A agonists oxymetazoline and apraclonidine in the form of topical eye drops can help with ptosis. “They potentially avoid some of the systemic toxicity of the other medications,” Ginsberg said. “So they might be an option if you’re really just trying to target ptosis as a symptom.”
However, it can be difficult to get insurers to cover these medications, he said.
The 13-year-old patient initially improved but developed difficulty walking. “Her hands began to feel heavy, and she had difficulty chewing and nasal regurgitation. On her exam, she still had fatigable ptosis plus hypernasal speech and generalized weakness. At this point, we’re starting to see that she has generalized myasthenia gravis that may be an impending crisis.”
The Young Patient Worsens. Now What?
The patient was admitted and given intravenous immunoglobulin at 2 g/kg over a couple days. But her symptoms worsened following initial improvement.
Glucocorticoids can play a larger role in treatment at this stage, and the patient was initially on prednisone. But there are reasons for caution, including effects on bone growth and interference with live vaccines.
However, live vaccines aren’t common in children, with the exception of the MMRV vaccine, he said. “It’s worth noting that you can give that second dose as early as 3 months after the initial one, so most patients really should be able to complete a course before they start on immunosuppression,” he said.
Another option is immunotherapy. “There’s a really large menu of options for immunotherapy in myasthenia gravis right now,” Ginsberg said. “It’s great that we have all these options, but it adds to the complexity.”
Rituximab may be considered based on early data, he said. And thymectomy — removal of the thymus gland — should be considered early.
Don’t Neglect Supportive Care
Ginsberg urged colleagues to consider supportive care measures. Advocacy groups such as the Myasthenia Gravis Foundation of America can help with weight management and diet/exercise counseling, especially in patients taking glucocorticoids.
He added that “school accommodations are very important in this age group. They might need a plan, for example, to have modified gym class or an excuse not to carry a book bag between classes.”
How did the 13-year-old do? She underwent thymectomy, and her disease remained stable after 6 months. “Her rituximab was discontinued,” Ginsberg said. “She considered participating in a clinical trial but then started seeing improvements. About a year after the thymectomy, she just stopped her steroids on her own, and she was fine.”
Ginsberg had no disclosures.
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA — At a pathophysiological level, juvenile myasthenia gravis (MG) seems to be identical to the adult form, neuromuscular specialists learned. But there are still important differences between children and their elders that affect pediatric care.
For example, “we have to think a little bit differently about the side effect profiles of the medications and their toxicity because children may react to medications differently,” said Matthew Ginsberg, MD, a pediatric neurologist based in Akron, Ohio, in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
And then there’s the matter of adherence. “It’s hard to get adults to take medication, but a teenager is sometimes an exceptional challenge,” Ginsberg said.
Case In Point: A 13-Year-Old With MG
Pediatric MG is rare. Cases in children are estimated to account for 10% of MG cases diagnosed each year. According to a 2020 report, “the majority will present with ptosis and a variable degree of ophthalmoplegia [paralysis of eye muscles].”
Ginsberg highlighted a case of a 13-year-old girl who’d been healthy but developed fatigable ptosis and mild restriction of extraocular movements. The patient’s acetylcholine receptor antibodies were very elevated, but she didn’t have MuSK antibodies.
“This isn’t a diagnostic conundrum. She has autoimmune myasthenia gravis with ocular manifestations,” Ginsberg said. “For someone like this, whether it’s an adult or a child, many people would start symptomatic treatment with an acetylcholinesterase inhibitor like pyridostigmine.”
The use of the drug in children is similar to that in adults, he said, although weight-based dosing is used. “Usually it’s around 3-7 mg/kg/d, but it’s still very individualized based on patient response.” The timing of symptoms can affect the distribution of doses throughout the day, he said.
“There are extended-release formulations of the medication, and I think some people use them more than I do,” he said. “The side effects are basically similar to adults. Most of the patients I have on it tolerate it really well and don’t have a lot of the muscarinic side effects that you would expect.”
Consider Prescription Eye Drops for Ptosis
Alpha-1A agonists oxymetazoline and apraclonidine in the form of topical eye drops can help with ptosis. “They potentially avoid some of the systemic toxicity of the other medications,” Ginsberg said. “So they might be an option if you’re really just trying to target ptosis as a symptom.”
However, it can be difficult to get insurers to cover these medications, he said.
The 13-year-old patient initially improved but developed difficulty walking. “Her hands began to feel heavy, and she had difficulty chewing and nasal regurgitation. On her exam, she still had fatigable ptosis plus hypernasal speech and generalized weakness. At this point, we’re starting to see that she has generalized myasthenia gravis that may be an impending crisis.”
The Young Patient Worsens. Now What?
The patient was admitted and given intravenous immunoglobulin at 2 g/kg over a couple days. But her symptoms worsened following initial improvement.
Glucocorticoids can play a larger role in treatment at this stage, and the patient was initially on prednisone. But there are reasons for caution, including effects on bone growth and interference with live vaccines.
However, live vaccines aren’t common in children, with the exception of the MMRV vaccine, he said. “It’s worth noting that you can give that second dose as early as 3 months after the initial one, so most patients really should be able to complete a course before they start on immunosuppression,” he said.
Another option is immunotherapy. “There’s a really large menu of options for immunotherapy in myasthenia gravis right now,” Ginsberg said. “It’s great that we have all these options, but it adds to the complexity.”
Rituximab may be considered based on early data, he said. And thymectomy — removal of the thymus gland — should be considered early.
Don’t Neglect Supportive Care
Ginsberg urged colleagues to consider supportive care measures. Advocacy groups such as the Myasthenia Gravis Foundation of America can help with weight management and diet/exercise counseling, especially in patients taking glucocorticoids.
He added that “school accommodations are very important in this age group. They might need a plan, for example, to have modified gym class or an excuse not to carry a book bag between classes.”
How did the 13-year-old do? She underwent thymectomy, and her disease remained stable after 6 months. “Her rituximab was discontinued,” Ginsberg said. “She considered participating in a clinical trial but then started seeing improvements. About a year after the thymectomy, she just stopped her steroids on her own, and she was fine.”
Ginsberg had no disclosures.
A version of this article appeared on Medscape.com.
FROM AANEM 2024
FDA OKs Novel Levodopa-Based Continuous Sub-Q Regimen for Parkinson’s Disease
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.