Rheumatoid Arthritis

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Fully 48% of patients with autoimmune rheumatic diseases who developed persistent hypogammaglobulinemia after initiating treatment with immunomodulatory agents harbored gene variants associated with inborn errors of immunity, according to the findings of a single-center study published in Annals of the Rheumatic Diseases.

The results raise the possibility of a shared genetic etiology between “primary” and “secondary” hypogammaglobulinemia and suggest that some cases of autoimmune rheumatic disease may result from inborn errors of immunity. “In other words, a rheumatologist may be treating the rheumatic manifestations of a primary immunodeficiency disorder,” the study’s lead author, Georgios Sogkas, MD, PhD, said in an interview.

‘Striking’ findings suggest a future in personalized medicine

Experts who were not involved in the study called the results noteworthy. “The fact that half of patients with rheumatic disease who developed secondary hypogammaglobulinemia were found to have a functionally relevant mutation in a known PID gene is striking, albeit purely circumstantial given the absence of any functional or mechanistic data,” said Michael J. Ombrello, MD, principal investigator and head of the translational genetics and genomics unit at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study.

The findings, if they are validated by additional studies, might help clinicians personalize medicine by avoiding hypogammaglobulinemia-inducing immunomodulatory regimens in genetically predisposed patients, or by targeting Janus kinase (JAK) inhibitor therapy for patients with STAT3 gain-of-function variants, or PI3K delta inhibitors for patients with variants leading to hyperactivation of the PI3Kdelta gene, Dr. Sogkas said.

Dr. Ombrello agreed: “Whether the hypogammaglobulinemia is classified as primary or secondary, the presence of these genetic variants in half of patients with hypogammaglobulinemia suggests an opportunity to improve clinical care. Although far off at this point, one can imagine a day where genetic data allows a rheumatologist to identify new-onset rheumatic disease patients carrying PID gene mutations and cater their therapy and monitoring accordingly.”

If further research validates these findings, they would add to a growing body of support for incorporating expanded or universal exome or genome sequencing in the care of medically complex patients, such as those with rheumatic diseases, Dr. Ombrello said. However, he cautioned that the investigators could have “overstated” the relationship in their study between secondary hypogammaglobulinemia and immunomodulatory treatment. The fact that a small group of study participants (about 7%) developed hypogammaglobulinemia after initiating immunomodulatory therapy does not confirm a causal relationship, he emphasized. Common variable immune deficiency (CVID) can develop in adults as late as the fifth and sixth decade of life, he noted, making it “not implausible that a small number of rheumatic disease patients would develop CVID while under the care of a rheumatologist. Would these patients have developed hypogammaglobulinemia even without treatment with immunomodulators, purely related to their genetic mutations? If so, they would be better classified as having primary immune deficiency, although that distinction is largely one of semantics.”

‘Rheumatologists are obliged to step up’

Interestingly, only 23% of the patients with hypogammaglobulinemia in the study had a clinically significant history of infections even though only 9% were receiving prophylactic antibiotics. Such findings highlight the complexity of PIDs, according to experts. “A long generation ago, we thought of immunodeficiencies as infections. Now we see them as autoimmune diseases, inflammatory diseases, allergic diseases – the spectrum continues to enlarge,” said Leonard H. Calabrese, DO, the RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, who was not involved in the study.

Dr. Calabrese noted that more than 450 monogenic variants have been linked to inborn errors of immunity. “Because these [PIDs] can mimic autoinflammatory presentations, rheumatologists are obliged to step up and gain a greater understanding, to be able to recognize and diagnose them and sort them out.”

Future goals should include quantifying the prevalence of genetic variants underlying hypogammaglobulinemia among patients with rheumatic diseases, and better characterizing outcomes and phenotypes of patients harboring variants linked to inborn errors of immunity, Dr. Sogkas said. “Whether these patients actually have a different disease than what they are being treated for, I can’t tell from this paper, and that’s an important question for the future,” added Dr. Calabrese. “I also do wonder about the effects of different drugs,” he said, noting that many patients with PID-associated autosomal gene variants developed persistent secondary hypogammaglobulinemia after initiating methotrexate. “It makes me wonder whether some of these genes have a specific interaction with methotrexate,” he said. “That could be a biomarker for drug toxicity.”

Study funders included the German Research Foundation, the German multiorgan Autoimmunity Network, Hannover Medical School, the Rosemarie-Germscheid Foundation, the German Academic Exchange Service, HBRS, the Center for Infection Biology, and the German Center for Infection Research. The investigators reported having no competing interests.

SOURCE: Sogkas G et al. Ann Rheum Dis. 2020 Oct 12. doi: 10.1136/annrheumdis-2020-218280.

Fully 48% of patients with autoimmune rheumatic diseases who developed persistent hypogammaglobulinemia after initiating treatment with immunomodulatory agents harbored gene variants associated with inborn errors of immunity, according to the findings of a single-center study published in Annals of the Rheumatic Diseases.

The results raise the possibility of a shared genetic etiology between “primary” and “secondary” hypogammaglobulinemia and suggest that some cases of autoimmune rheumatic disease may result from inborn errors of immunity. “In other words, a rheumatologist may be treating the rheumatic manifestations of a primary immunodeficiency disorder,” the study’s lead author, Georgios Sogkas, MD, PhD, said in an interview.

‘Striking’ findings suggest a future in personalized medicine

Experts who were not involved in the study called the results noteworthy. “The fact that half of patients with rheumatic disease who developed secondary hypogammaglobulinemia were found to have a functionally relevant mutation in a known PID gene is striking, albeit purely circumstantial given the absence of any functional or mechanistic data,” said Michael J. Ombrello, MD, principal investigator and head of the translational genetics and genomics unit at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study.

The findings, if they are validated by additional studies, might help clinicians personalize medicine by avoiding hypogammaglobulinemia-inducing immunomodulatory regimens in genetically predisposed patients, or by targeting Janus kinase (JAK) inhibitor therapy for patients with STAT3 gain-of-function variants, or PI3K delta inhibitors for patients with variants leading to hyperactivation of the PI3Kdelta gene, Dr. Sogkas said.

Dr. Ombrello agreed: “Whether the hypogammaglobulinemia is classified as primary or secondary, the presence of these genetic variants in half of patients with hypogammaglobulinemia suggests an opportunity to improve clinical care. Although far off at this point, one can imagine a day where genetic data allows a rheumatologist to identify new-onset rheumatic disease patients carrying PID gene mutations and cater their therapy and monitoring accordingly.”

If further research validates these findings, they would add to a growing body of support for incorporating expanded or universal exome or genome sequencing in the care of medically complex patients, such as those with rheumatic diseases, Dr. Ombrello said. However, he cautioned that the investigators could have “overstated” the relationship in their study between secondary hypogammaglobulinemia and immunomodulatory treatment. The fact that a small group of study participants (about 7%) developed hypogammaglobulinemia after initiating immunomodulatory therapy does not confirm a causal relationship, he emphasized. Common variable immune deficiency (CVID) can develop in adults as late as the fifth and sixth decade of life, he noted, making it “not implausible that a small number of rheumatic disease patients would develop CVID while under the care of a rheumatologist. Would these patients have developed hypogammaglobulinemia even without treatment with immunomodulators, purely related to their genetic mutations? If so, they would be better classified as having primary immune deficiency, although that distinction is largely one of semantics.”

‘Rheumatologists are obliged to step up’

Interestingly, only 23% of the patients with hypogammaglobulinemia in the study had a clinically significant history of infections even though only 9% were receiving prophylactic antibiotics. Such findings highlight the complexity of PIDs, according to experts. “A long generation ago, we thought of immunodeficiencies as infections. Now we see them as autoimmune diseases, inflammatory diseases, allergic diseases – the spectrum continues to enlarge,” said Leonard H. Calabrese, DO, the RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, who was not involved in the study.

Dr. Calabrese noted that more than 450 monogenic variants have been linked to inborn errors of immunity. “Because these [PIDs] can mimic autoinflammatory presentations, rheumatologists are obliged to step up and gain a greater understanding, to be able to recognize and diagnose them and sort them out.”

Future goals should include quantifying the prevalence of genetic variants underlying hypogammaglobulinemia among patients with rheumatic diseases, and better characterizing outcomes and phenotypes of patients harboring variants linked to inborn errors of immunity, Dr. Sogkas said. “Whether these patients actually have a different disease than what they are being treated for, I can’t tell from this paper, and that’s an important question for the future,” added Dr. Calabrese. “I also do wonder about the effects of different drugs,” he said, noting that many patients with PID-associated autosomal gene variants developed persistent secondary hypogammaglobulinemia after initiating methotrexate. “It makes me wonder whether some of these genes have a specific interaction with methotrexate,” he said. “That could be a biomarker for drug toxicity.”

Study funders included the German Research Foundation, the German multiorgan Autoimmunity Network, Hannover Medical School, the Rosemarie-Germscheid Foundation, the German Academic Exchange Service, HBRS, the Center for Infection Biology, and the German Center for Infection Research. The investigators reported having no competing interests.

SOURCE: Sogkas G et al. Ann Rheum Dis. 2020 Oct 12. doi: 10.1136/annrheumdis-2020-218280.

Fully 48% of patients with autoimmune rheumatic diseases who developed persistent hypogammaglobulinemia after initiating treatment with immunomodulatory agents harbored gene variants associated with inborn errors of immunity, according to the findings of a single-center study published in Annals of the Rheumatic Diseases.

The results raise the possibility of a shared genetic etiology between “primary” and “secondary” hypogammaglobulinemia and suggest that some cases of autoimmune rheumatic disease may result from inborn errors of immunity. “In other words, a rheumatologist may be treating the rheumatic manifestations of a primary immunodeficiency disorder,” the study’s lead author, Georgios Sogkas, MD, PhD, said in an interview.

‘Striking’ findings suggest a future in personalized medicine

Experts who were not involved in the study called the results noteworthy. “The fact that half of patients with rheumatic disease who developed secondary hypogammaglobulinemia were found to have a functionally relevant mutation in a known PID gene is striking, albeit purely circumstantial given the absence of any functional or mechanistic data,” said Michael J. Ombrello, MD, principal investigator and head of the translational genetics and genomics unit at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study.

The findings, if they are validated by additional studies, might help clinicians personalize medicine by avoiding hypogammaglobulinemia-inducing immunomodulatory regimens in genetically predisposed patients, or by targeting Janus kinase (JAK) inhibitor therapy for patients with STAT3 gain-of-function variants, or PI3K delta inhibitors for patients with variants leading to hyperactivation of the PI3Kdelta gene, Dr. Sogkas said.

Dr. Ombrello agreed: “Whether the hypogammaglobulinemia is classified as primary or secondary, the presence of these genetic variants in half of patients with hypogammaglobulinemia suggests an opportunity to improve clinical care. Although far off at this point, one can imagine a day where genetic data allows a rheumatologist to identify new-onset rheumatic disease patients carrying PID gene mutations and cater their therapy and monitoring accordingly.”

If further research validates these findings, they would add to a growing body of support for incorporating expanded or universal exome or genome sequencing in the care of medically complex patients, such as those with rheumatic diseases, Dr. Ombrello said. However, he cautioned that the investigators could have “overstated” the relationship in their study between secondary hypogammaglobulinemia and immunomodulatory treatment. The fact that a small group of study participants (about 7%) developed hypogammaglobulinemia after initiating immunomodulatory therapy does not confirm a causal relationship, he emphasized. Common variable immune deficiency (CVID) can develop in adults as late as the fifth and sixth decade of life, he noted, making it “not implausible that a small number of rheumatic disease patients would develop CVID while under the care of a rheumatologist. Would these patients have developed hypogammaglobulinemia even without treatment with immunomodulators, purely related to their genetic mutations? If so, they would be better classified as having primary immune deficiency, although that distinction is largely one of semantics.”

‘Rheumatologists are obliged to step up’

Interestingly, only 23% of the patients with hypogammaglobulinemia in the study had a clinically significant history of infections even though only 9% were receiving prophylactic antibiotics. Such findings highlight the complexity of PIDs, according to experts. “A long generation ago, we thought of immunodeficiencies as infections. Now we see them as autoimmune diseases, inflammatory diseases, allergic diseases – the spectrum continues to enlarge,” said Leonard H. Calabrese, DO, the RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, who was not involved in the study.

Dr. Calabrese noted that more than 450 monogenic variants have been linked to inborn errors of immunity. “Because these [PIDs] can mimic autoinflammatory presentations, rheumatologists are obliged to step up and gain a greater understanding, to be able to recognize and diagnose them and sort them out.”

Future goals should include quantifying the prevalence of genetic variants underlying hypogammaglobulinemia among patients with rheumatic diseases, and better characterizing outcomes and phenotypes of patients harboring variants linked to inborn errors of immunity, Dr. Sogkas said. “Whether these patients actually have a different disease than what they are being treated for, I can’t tell from this paper, and that’s an important question for the future,” added Dr. Calabrese. “I also do wonder about the effects of different drugs,” he said, noting that many patients with PID-associated autosomal gene variants developed persistent secondary hypogammaglobulinemia after initiating methotrexate. “It makes me wonder whether some of these genes have a specific interaction with methotrexate,” he said. “That could be a biomarker for drug toxicity.”

Study funders included the German Research Foundation, the German multiorgan Autoimmunity Network, Hannover Medical School, the Rosemarie-Germscheid Foundation, the German Academic Exchange Service, HBRS, the Center for Infection Biology, and the German Center for Infection Research. The investigators reported having no competing interests.

SOURCE: Sogkas G et al. Ann Rheum Dis. 2020 Oct 12. doi: 10.1136/annrheumdis-2020-218280.

The U.S. Food and Drug Administration released new warnings Oct. 15 that most nonsteroidal anti-inflammatory agents (NSAIDs) carry an elevated risk for kidney complications in unborn children when taken around weeks 20 or later in pregnancy.

Citing newly available research, the agency states the risk of low amniotic fluid (known as oligohydramnios) can occur, which in turn can cause rare but serious kidney problems in the offspring. Pregnancy complications also can result.

The FDA action expands on earlier warnings about agents in this drug class, which the FDA previously cautioned about taking after week 30 of pregnancy because of heart-related risks.

Manufacturers of both over-the-counter and prescription NSAIDs – including ibuprofen, naproxen, diclofenac, and celecoxib – will be required to update their labeling with the new warning.

Low-dose (81-mg) aspirin is excluded from this warning.

“Low-dose aspirin may be an important treatment for some women during pregnancy and should be taken under the direction of a healthcare professional,” the agency stated in a news release.

“It is important that women understand the benefits and risks of the medications they may take over the course of their pregnancy,” Patrizia Cavazzoni, MD, acting director of FDA’s Center for Drug Evaluation and Research, states in the release. “To this end, the agency is using its regulatory authority to inform women and their healthcare providers about the risks if NSAIDs are used after around 20 weeks of pregnancy and beyond.”

Oligohydramnios can arise quickly – in as little as 2 days – or weeks after starting regular NSAID use in this patient population. The condition usually resolves if a pregnant woman stops taking the NSAID, the agency notes.

If a health care provider believes NSAIDs are necessary between about 20 and 30 weeks of pregnancy, use should be limited to the lowest effective dose and shortest duration possible, the Drug Safety Communication notes.

As a reminder, health care professionals and patients should report side effects from NSAIDs to the FDA’s MedWatch program.

A version of this article originally appeared on Medscape.com.

The U.S. Food and Drug Administration released new warnings Oct. 15 that most nonsteroidal anti-inflammatory agents (NSAIDs) carry an elevated risk for kidney complications in unborn children when taken around weeks 20 or later in pregnancy.

Citing newly available research, the agency states the risk of low amniotic fluid (known as oligohydramnios) can occur, which in turn can cause rare but serious kidney problems in the offspring. Pregnancy complications also can result.

The FDA action expands on earlier warnings about agents in this drug class, which the FDA previously cautioned about taking after week 30 of pregnancy because of heart-related risks.

Manufacturers of both over-the-counter and prescription NSAIDs – including ibuprofen, naproxen, diclofenac, and celecoxib – will be required to update their labeling with the new warning.

Low-dose (81-mg) aspirin is excluded from this warning.

“Low-dose aspirin may be an important treatment for some women during pregnancy and should be taken under the direction of a healthcare professional,” the agency stated in a news release.

“It is important that women understand the benefits and risks of the medications they may take over the course of their pregnancy,” Patrizia Cavazzoni, MD, acting director of FDA’s Center for Drug Evaluation and Research, states in the release. “To this end, the agency is using its regulatory authority to inform women and their healthcare providers about the risks if NSAIDs are used after around 20 weeks of pregnancy and beyond.”

Oligohydramnios can arise quickly – in as little as 2 days – or weeks after starting regular NSAID use in this patient population. The condition usually resolves if a pregnant woman stops taking the NSAID, the agency notes.

If a health care provider believes NSAIDs are necessary between about 20 and 30 weeks of pregnancy, use should be limited to the lowest effective dose and shortest duration possible, the Drug Safety Communication notes.

As a reminder, health care professionals and patients should report side effects from NSAIDs to the FDA’s MedWatch program.

A version of this article originally appeared on Medscape.com.

The U.S. Food and Drug Administration released new warnings Oct. 15 that most nonsteroidal anti-inflammatory agents (NSAIDs) carry an elevated risk for kidney complications in unborn children when taken around weeks 20 or later in pregnancy.

Citing newly available research, the agency states the risk of low amniotic fluid (known as oligohydramnios) can occur, which in turn can cause rare but serious kidney problems in the offspring. Pregnancy complications also can result.

The FDA action expands on earlier warnings about agents in this drug class, which the FDA previously cautioned about taking after week 30 of pregnancy because of heart-related risks.

Manufacturers of both over-the-counter and prescription NSAIDs – including ibuprofen, naproxen, diclofenac, and celecoxib – will be required to update their labeling with the new warning.

Low-dose (81-mg) aspirin is excluded from this warning.

“Low-dose aspirin may be an important treatment for some women during pregnancy and should be taken under the direction of a healthcare professional,” the agency stated in a news release.

“It is important that women understand the benefits and risks of the medications they may take over the course of their pregnancy,” Patrizia Cavazzoni, MD, acting director of FDA’s Center for Drug Evaluation and Research, states in the release. “To this end, the agency is using its regulatory authority to inform women and their healthcare providers about the risks if NSAIDs are used after around 20 weeks of pregnancy and beyond.”

Oligohydramnios can arise quickly – in as little as 2 days – or weeks after starting regular NSAID use in this patient population. The condition usually resolves if a pregnant woman stops taking the NSAID, the agency notes.

If a health care provider believes NSAIDs are necessary between about 20 and 30 weeks of pregnancy, use should be limited to the lowest effective dose and shortest duration possible, the Drug Safety Communication notes.

As a reminder, health care professionals and patients should report side effects from NSAIDs to the FDA’s MedWatch program.

A version of this article originally appeared on Medscape.com.

Upadacitinib (Rinvoq) proved superior to abatacept in both disease activity and remission in rheumatoid arthritis patients yet led to more adverse events, according to a new study that compared the two drugs.

“Additional data from longer and larger trials are needed to better understand long-term outcomes and safety of upadacitinib as compared with other drugs for the treatment of rheumatoid arthritis,” wrote Andrea Rubbert-Roth, MD, of the Cantonal Clinic St. Gallen in St. Gallen, Switzerland, and her colleagues. The study was published in the New England Journal of Medicine.

The Food and Drug Administration approved upadacitinib for the treatment of rheumatoid arthritis in August 2019.

To compare the Janus kinase (JAK) inhibitor upadacitinib and the biologic disease-modifying antirheumatic drug (DMARD) abatacept as safe and effective treatments for RA, the researchers launched a randomized, double-blind, phase 3 clinical trial dubbed SELECT-CHOICE at 120 sites in 28 countries. All patients had moderate to severe active disease after previously having inadequate responses to at least one biologic DMARD. Slightly more than 82% of the participants were female, with a mean age of 55 years and mean RA duration of 12 years.

Patients were assigned either 15 mg of oral upadacitinib daily (n = 303) or intravenous abatacept at day 1 and weeks 2, 4, 8, 12, 16 and 20 (n = 309) with dosage tied to body weight, each in combination with stable synthetic DMARDs. Disease activity was measured after 12 weeks via the Disease Activity Score for 28 joints using C-reactive protein (DAS28-CRP). A DAS28-CRP of more than 5.1 was categorized as high disease activity, while 3.2-5.1 meant moderate disease activity, 2.6-3.2 meant low disease activity, and less than 2.6 indicated remission.

The mean DAS28-CRP at baseline was 5.70 in the upadacitinib group and 5.88 in the abatacept group. After 12 weeks, the mean change from baseline was –2.52 points and –2.00 points, respectively (difference, –0.52 points; 95% confidence interval, –0.69 to –0.35; P < .001 for noninferiority; P < .001 for superiority). In patients with a DAS28-CRP of less than 2.6, the percentage of those having remission was 30% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P < .001 for superiority).

Over the 24-week trial period, the incidence of all adverse events (209 vs. 189) and serious adverse events (10 vs. 5) was higher in the upadacitinib group than in the abatacept group. There were 23 cases of hepatic disorder with upadacitinib, compared with 5 with abatacept; 2 thromboembolic events with upadacitinib, compared with 0 with abatacept; and 2 deaths with upadacitinib, compared with 1 with abatacept.

“The thing that bothers me, actually, is the adverse events,” Daniel E. Furst, MD, professor of medicine (emeritus) and rheumatology at the University of California, Los Angeles, said in an interview. “There were a fair number of them, all of which were a little higher in upadacitinib. They certainly made very little of those.”

He noted several other concerns about the study, including a potential geographic effect stemming from 60% of the study’s centers being in South and Central America and Eastern Europe. “Those patients don’t always have very good medical care,” he said. “They have an inherent, underlying placebo response that can be much different than Western Europe and North America.”

He also questioned their choice of primary endpoint metric.

“I think a much more legitimate way at looking at remission is the CDAI [Clinical Disease Activity Index] rather than the DAS28,” he said. “The DAS28, even at its best, is low disease activity, not true remission.”

“Bottom line,” he added, “this is a legitimate study that supports previous findings. One more important thing that is overlooked, though, is an economic analysis. A true economic analysis would be very important to place this in the armamentarium.”
 

Study affirms upadacitinib’s place in the RA treatment pecking order

By showing that upadacitinib was not only noninferior but superior to abatacept in decreasing disease activity, Rubbert-Roth and colleagues have positioned the JAK inhibitor at “the forefront of treatment for rheumatoid arthritis,” wrote Guro L. Goll, MD, PhD, and Tore K. Kvien, MD, PhD, of Diakonhjemmet Hospital in Oslo, in an accompanying editorial.

Though the authors noted that the 24-week trial was likely too short to make meaningful assumptions about long-term outcomes, they recognized the notably improved treatment outcomes over the study period and stated the importance of “head-to-head trials ... to inform evidence-based clinical decisions.” Similar to Dr. Furst, however, they stated an interest in “detailed data on changes in the CDAI score as a continuous measure.”

They also acknowledged the significant increase in adverse events among patients in the upadacitinib group, underlining the need to learn more in forthcoming, lengthier trials. “Rheumatologists will be looking hard at future data,” they wrote, “to assess whether improved treatment outcomes justify an increased risk of adverse events.”

The study was supported by AbbVie. The authors acknowledged numerous potential conflicts of interest, including receiving research grants and fees from various pharmaceutical companies for consulting, lectures, and being on advisory boards.

SOURCE: Rubbert-Roth A et al. N Engl J Med. 2020 Oct 14. doi: 10.1056/NEJMoa2008250.

Upadacitinib (Rinvoq) proved superior to abatacept in both disease activity and remission in rheumatoid arthritis patients yet led to more adverse events, according to a new study that compared the two drugs.

“Additional data from longer and larger trials are needed to better understand long-term outcomes and safety of upadacitinib as compared with other drugs for the treatment of rheumatoid arthritis,” wrote Andrea Rubbert-Roth, MD, of the Cantonal Clinic St. Gallen in St. Gallen, Switzerland, and her colleagues. The study was published in the New England Journal of Medicine.

The Food and Drug Administration approved upadacitinib for the treatment of rheumatoid arthritis in August 2019.

To compare the Janus kinase (JAK) inhibitor upadacitinib and the biologic disease-modifying antirheumatic drug (DMARD) abatacept as safe and effective treatments for RA, the researchers launched a randomized, double-blind, phase 3 clinical trial dubbed SELECT-CHOICE at 120 sites in 28 countries. All patients had moderate to severe active disease after previously having inadequate responses to at least one biologic DMARD. Slightly more than 82% of the participants were female, with a mean age of 55 years and mean RA duration of 12 years.

Patients were assigned either 15 mg of oral upadacitinib daily (n = 303) or intravenous abatacept at day 1 and weeks 2, 4, 8, 12, 16 and 20 (n = 309) with dosage tied to body weight, each in combination with stable synthetic DMARDs. Disease activity was measured after 12 weeks via the Disease Activity Score for 28 joints using C-reactive protein (DAS28-CRP). A DAS28-CRP of more than 5.1 was categorized as high disease activity, while 3.2-5.1 meant moderate disease activity, 2.6-3.2 meant low disease activity, and less than 2.6 indicated remission.

The mean DAS28-CRP at baseline was 5.70 in the upadacitinib group and 5.88 in the abatacept group. After 12 weeks, the mean change from baseline was –2.52 points and –2.00 points, respectively (difference, –0.52 points; 95% confidence interval, –0.69 to –0.35; P < .001 for noninferiority; P < .001 for superiority). In patients with a DAS28-CRP of less than 2.6, the percentage of those having remission was 30% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P < .001 for superiority).

Over the 24-week trial period, the incidence of all adverse events (209 vs. 189) and serious adverse events (10 vs. 5) was higher in the upadacitinib group than in the abatacept group. There were 23 cases of hepatic disorder with upadacitinib, compared with 5 with abatacept; 2 thromboembolic events with upadacitinib, compared with 0 with abatacept; and 2 deaths with upadacitinib, compared with 1 with abatacept.

“The thing that bothers me, actually, is the adverse events,” Daniel E. Furst, MD, professor of medicine (emeritus) and rheumatology at the University of California, Los Angeles, said in an interview. “There were a fair number of them, all of which were a little higher in upadacitinib. They certainly made very little of those.”

He noted several other concerns about the study, including a potential geographic effect stemming from 60% of the study’s centers being in South and Central America and Eastern Europe. “Those patients don’t always have very good medical care,” he said. “They have an inherent, underlying placebo response that can be much different than Western Europe and North America.”

He also questioned their choice of primary endpoint metric.

“I think a much more legitimate way at looking at remission is the CDAI [Clinical Disease Activity Index] rather than the DAS28,” he said. “The DAS28, even at its best, is low disease activity, not true remission.”

“Bottom line,” he added, “this is a legitimate study that supports previous findings. One more important thing that is overlooked, though, is an economic analysis. A true economic analysis would be very important to place this in the armamentarium.”
 

Study affirms upadacitinib’s place in the RA treatment pecking order

By showing that upadacitinib was not only noninferior but superior to abatacept in decreasing disease activity, Rubbert-Roth and colleagues have positioned the JAK inhibitor at “the forefront of treatment for rheumatoid arthritis,” wrote Guro L. Goll, MD, PhD, and Tore K. Kvien, MD, PhD, of Diakonhjemmet Hospital in Oslo, in an accompanying editorial.

Though the authors noted that the 24-week trial was likely too short to make meaningful assumptions about long-term outcomes, they recognized the notably improved treatment outcomes over the study period and stated the importance of “head-to-head trials ... to inform evidence-based clinical decisions.” Similar to Dr. Furst, however, they stated an interest in “detailed data on changes in the CDAI score as a continuous measure.”

They also acknowledged the significant increase in adverse events among patients in the upadacitinib group, underlining the need to learn more in forthcoming, lengthier trials. “Rheumatologists will be looking hard at future data,” they wrote, “to assess whether improved treatment outcomes justify an increased risk of adverse events.”

The study was supported by AbbVie. The authors acknowledged numerous potential conflicts of interest, including receiving research grants and fees from various pharmaceutical companies for consulting, lectures, and being on advisory boards.

SOURCE: Rubbert-Roth A et al. N Engl J Med. 2020 Oct 14. doi: 10.1056/NEJMoa2008250.

Upadacitinib (Rinvoq) proved superior to abatacept in both disease activity and remission in rheumatoid arthritis patients yet led to more adverse events, according to a new study that compared the two drugs.

“Additional data from longer and larger trials are needed to better understand long-term outcomes and safety of upadacitinib as compared with other drugs for the treatment of rheumatoid arthritis,” wrote Andrea Rubbert-Roth, MD, of the Cantonal Clinic St. Gallen in St. Gallen, Switzerland, and her colleagues. The study was published in the New England Journal of Medicine.

The Food and Drug Administration approved upadacitinib for the treatment of rheumatoid arthritis in August 2019.

To compare the Janus kinase (JAK) inhibitor upadacitinib and the biologic disease-modifying antirheumatic drug (DMARD) abatacept as safe and effective treatments for RA, the researchers launched a randomized, double-blind, phase 3 clinical trial dubbed SELECT-CHOICE at 120 sites in 28 countries. All patients had moderate to severe active disease after previously having inadequate responses to at least one biologic DMARD. Slightly more than 82% of the participants were female, with a mean age of 55 years and mean RA duration of 12 years.

Patients were assigned either 15 mg of oral upadacitinib daily (n = 303) or intravenous abatacept at day 1 and weeks 2, 4, 8, 12, 16 and 20 (n = 309) with dosage tied to body weight, each in combination with stable synthetic DMARDs. Disease activity was measured after 12 weeks via the Disease Activity Score for 28 joints using C-reactive protein (DAS28-CRP). A DAS28-CRP of more than 5.1 was categorized as high disease activity, while 3.2-5.1 meant moderate disease activity, 2.6-3.2 meant low disease activity, and less than 2.6 indicated remission.

The mean DAS28-CRP at baseline was 5.70 in the upadacitinib group and 5.88 in the abatacept group. After 12 weeks, the mean change from baseline was –2.52 points and –2.00 points, respectively (difference, –0.52 points; 95% confidence interval, –0.69 to –0.35; P < .001 for noninferiority; P < .001 for superiority). In patients with a DAS28-CRP of less than 2.6, the percentage of those having remission was 30% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P < .001 for superiority).

Over the 24-week trial period, the incidence of all adverse events (209 vs. 189) and serious adverse events (10 vs. 5) was higher in the upadacitinib group than in the abatacept group. There were 23 cases of hepatic disorder with upadacitinib, compared with 5 with abatacept; 2 thromboembolic events with upadacitinib, compared with 0 with abatacept; and 2 deaths with upadacitinib, compared with 1 with abatacept.

“The thing that bothers me, actually, is the adverse events,” Daniel E. Furst, MD, professor of medicine (emeritus) and rheumatology at the University of California, Los Angeles, said in an interview. “There were a fair number of them, all of which were a little higher in upadacitinib. They certainly made very little of those.”

He noted several other concerns about the study, including a potential geographic effect stemming from 60% of the study’s centers being in South and Central America and Eastern Europe. “Those patients don’t always have very good medical care,” he said. “They have an inherent, underlying placebo response that can be much different than Western Europe and North America.”

He also questioned their choice of primary endpoint metric.

“I think a much more legitimate way at looking at remission is the CDAI [Clinical Disease Activity Index] rather than the DAS28,” he said. “The DAS28, even at its best, is low disease activity, not true remission.”

“Bottom line,” he added, “this is a legitimate study that supports previous findings. One more important thing that is overlooked, though, is an economic analysis. A true economic analysis would be very important to place this in the armamentarium.”
 

Study affirms upadacitinib’s place in the RA treatment pecking order

By showing that upadacitinib was not only noninferior but superior to abatacept in decreasing disease activity, Rubbert-Roth and colleagues have positioned the JAK inhibitor at “the forefront of treatment for rheumatoid arthritis,” wrote Guro L. Goll, MD, PhD, and Tore K. Kvien, MD, PhD, of Diakonhjemmet Hospital in Oslo, in an accompanying editorial.

Though the authors noted that the 24-week trial was likely too short to make meaningful assumptions about long-term outcomes, they recognized the notably improved treatment outcomes over the study period and stated the importance of “head-to-head trials ... to inform evidence-based clinical decisions.” Similar to Dr. Furst, however, they stated an interest in “detailed data on changes in the CDAI score as a continuous measure.”

They also acknowledged the significant increase in adverse events among patients in the upadacitinib group, underlining the need to learn more in forthcoming, lengthier trials. “Rheumatologists will be looking hard at future data,” they wrote, “to assess whether improved treatment outcomes justify an increased risk of adverse events.”

The study was supported by AbbVie. The authors acknowledged numerous potential conflicts of interest, including receiving research grants and fees from various pharmaceutical companies for consulting, lectures, and being on advisory boards.

SOURCE: Rubbert-Roth A et al. N Engl J Med. 2020 Oct 14. doi: 10.1056/NEJMoa2008250.

In a new review, a group of infectious disease experts have summarized and made recommendations about recent findings regarding infections that can occur during treatment with an evolving set of targeted and biologic therapies for rheumatoid arthritis and psoriatic arthritis.

“We claim for the need for multicenter registries and multidisciplinary approaches, for new vaccines trials in RA and PsA, and for better defining when and how biologics can be restarted after severe infections,” lead author Olivier Lortholary, MD, of the Institut Pasteur in Paris, and his coauthors wrote in Annals of the Rheumatic Diseases.

Assessing infection risk related to various inhibitors

Regarding infections caused by TNF-alpha inhibitors (TNFIs), the experts acknowledged a broad increase in risk for mycobacterial and fungal infections, especially tuberculosis and histoplasmosis. They added that patients on TNFIs are more prone to developing pneumonia and soft tissue infections, while smaller studies have indicated a higher risk of listeriosis, legionellosis, herpes zoster (HZ), and reactivation of chronic hepatitis B virus infection.

As for recommendations, they endorsed discontinuing TNFIs when a serious infection occurs and not restarting until after treatment and clinical response. Patients should be screened for latent tuberculosis infection (LTBI) before starting the drug, and anti-TB drugs should be presented to patients with LTBI so they do not progress to active TB.

Regarding other biologics, they cited several studies indicating that IL-6 inhibitors can increase infection risks in RA patients at a rate similar to TNFIs. Among the most common infections were pneumonia and cellulitis. In addition, although PsA patients on IL-17 inhibitors have a dose-dependent risk of mild to moderate mucocutaneous candidiasis, there was no increased risk of serious opportunistic infections like TB.

In assessing JAK inhibitors, they cited a pooled analysis that indicated pneumonia and skin and soft-tissue infections as the most common and noted the high incidence of HZ, compared with other infections. They added that abatacept (Orencia) did not appear to increase risk of infections in RA patients, such as HZ, dermatomycosis, candidiasis, or endemic mycoses. Those same patients did not see an increased overall infection risk after treatment with rituximab (Rituxan), and clinical trials containing treatment with apremilast (Otezla) reported a rare occurrence of serious infections.

Recommendation-wise, they endorsed screening for LTBI before starting IL-6 inhibitors and antiviral prophylaxis with acyclovir in particularly at-risk patients on JAK inhibitors. Age-appropriate influenza vaccinations were also recommended for rituximab, because of the development of rituximab-induced hypogammaglobulinemia.
 

Prediction and prevention

When it comes to predicting infections in patients on biologics, the experts wrote that it “remains a challenge.” The potential effects of pretreatment underlying disease, the lack of validated biomarkers, and the relatively low rate of infections all combine to stymie prediction. That said, they acknowledged ongoing efforts in monitoring lymphocyte subpopulation counts and immunoglobin levels, as well as a clinical score called the RABBIT Risk Score for Infections, which was validated in two separate cohorts.

“As Yogi Berra said, predictions are hard, especially about the future,” Dr. Kavanaugh said. “Discussions with your patient are always important.”

In regard to overall prevention, they acknowledged that most of their recommendations are of low evidence, except for antiviral prophylaxis for hepatitis B patients on rituximab and the aforementioned LTBI therapy in patients on TNFIs. Broadly, they advocated for all RA and PsA patients to receive a full infectious disease evaluation before the start of targeted and biologic therapies.

They also addressed vaccinations, recommending an evaluation of the patient’s immunization history and potentially planning a catch-up schedule for those in need of the influenza vaccine, a diphtheria-tetanus-pertussis booster, or the pneumococcal vaccine. More broadly, they stated that “a better response is expected if [non-live] vaccination is performed before the introduction of immunosuppressive drugs.” They added that live vaccines should be administered as soon as possible.
 

What rheumatologists can do

“So how do you mitigate risk?” Dr. Winthrop asked. “You have to be able to predict the risk, see what’s modifiable, and try to act on it. A lot of the risk of infection has more to do with the patient than the therapy.

“You try to minimize what you’re doing to the patient, particularly around steroids,” he said. “And then you think about screening and vaccinations. Rheumatologists need to be involved in those conversations because they’re the ones who know how these drugs interact with vaccines. A lot of the drugs might dumb down vaccine responses. Be sure to consider that and give the vaccines at times that will optimize their immunogenicity and likely efficacy.”

“Thankfully, infections are not that common,” Dr. Kavanaugh said. “Rheumatologists depend on data from trials, but more safety data comes from registry data and personal and shared experience.”

The authors declared no potential conflicts of interest.

SOURCE: Lortholary O et al. Ann Rheum Dis. 2020 Sep 22. doi: 10.1136/annrheumdis-2020-217092.

In a new review, a group of infectious disease experts have summarized and made recommendations about recent findings regarding infections that can occur during treatment with an evolving set of targeted and biologic therapies for rheumatoid arthritis and psoriatic arthritis.

“We claim for the need for multicenter registries and multidisciplinary approaches, for new vaccines trials in RA and PsA, and for better defining when and how biologics can be restarted after severe infections,” lead author Olivier Lortholary, MD, of the Institut Pasteur in Paris, and his coauthors wrote in Annals of the Rheumatic Diseases.

Assessing infection risk related to various inhibitors

Regarding infections caused by TNF-alpha inhibitors (TNFIs), the experts acknowledged a broad increase in risk for mycobacterial and fungal infections, especially tuberculosis and histoplasmosis. They added that patients on TNFIs are more prone to developing pneumonia and soft tissue infections, while smaller studies have indicated a higher risk of listeriosis, legionellosis, herpes zoster (HZ), and reactivation of chronic hepatitis B virus infection.

As for recommendations, they endorsed discontinuing TNFIs when a serious infection occurs and not restarting until after treatment and clinical response. Patients should be screened for latent tuberculosis infection (LTBI) before starting the drug, and anti-TB drugs should be presented to patients with LTBI so they do not progress to active TB.

Regarding other biologics, they cited several studies indicating that IL-6 inhibitors can increase infection risks in RA patients at a rate similar to TNFIs. Among the most common infections were pneumonia and cellulitis. In addition, although PsA patients on IL-17 inhibitors have a dose-dependent risk of mild to moderate mucocutaneous candidiasis, there was no increased risk of serious opportunistic infections like TB.

In assessing JAK inhibitors, they cited a pooled analysis that indicated pneumonia and skin and soft-tissue infections as the most common and noted the high incidence of HZ, compared with other infections. They added that abatacept (Orencia) did not appear to increase risk of infections in RA patients, such as HZ, dermatomycosis, candidiasis, or endemic mycoses. Those same patients did not see an increased overall infection risk after treatment with rituximab (Rituxan), and clinical trials containing treatment with apremilast (Otezla) reported a rare occurrence of serious infections.

Recommendation-wise, they endorsed screening for LTBI before starting IL-6 inhibitors and antiviral prophylaxis with acyclovir in particularly at-risk patients on JAK inhibitors. Age-appropriate influenza vaccinations were also recommended for rituximab, because of the development of rituximab-induced hypogammaglobulinemia.
 

Prediction and prevention

When it comes to predicting infections in patients on biologics, the experts wrote that it “remains a challenge.” The potential effects of pretreatment underlying disease, the lack of validated biomarkers, and the relatively low rate of infections all combine to stymie prediction. That said, they acknowledged ongoing efforts in monitoring lymphocyte subpopulation counts and immunoglobin levels, as well as a clinical score called the RABBIT Risk Score for Infections, which was validated in two separate cohorts.

“As Yogi Berra said, predictions are hard, especially about the future,” Dr. Kavanaugh said. “Discussions with your patient are always important.”

In regard to overall prevention, they acknowledged that most of their recommendations are of low evidence, except for antiviral prophylaxis for hepatitis B patients on rituximab and the aforementioned LTBI therapy in patients on TNFIs. Broadly, they advocated for all RA and PsA patients to receive a full infectious disease evaluation before the start of targeted and biologic therapies.

They also addressed vaccinations, recommending an evaluation of the patient’s immunization history and potentially planning a catch-up schedule for those in need of the influenza vaccine, a diphtheria-tetanus-pertussis booster, or the pneumococcal vaccine. More broadly, they stated that “a better response is expected if [non-live] vaccination is performed before the introduction of immunosuppressive drugs.” They added that live vaccines should be administered as soon as possible.
 

What rheumatologists can do

“So how do you mitigate risk?” Dr. Winthrop asked. “You have to be able to predict the risk, see what’s modifiable, and try to act on it. A lot of the risk of infection has more to do with the patient than the therapy.

“You try to minimize what you’re doing to the patient, particularly around steroids,” he said. “And then you think about screening and vaccinations. Rheumatologists need to be involved in those conversations because they’re the ones who know how these drugs interact with vaccines. A lot of the drugs might dumb down vaccine responses. Be sure to consider that and give the vaccines at times that will optimize their immunogenicity and likely efficacy.”

“Thankfully, infections are not that common,” Dr. Kavanaugh said. “Rheumatologists depend on data from trials, but more safety data comes from registry data and personal and shared experience.”

The authors declared no potential conflicts of interest.

SOURCE: Lortholary O et al. Ann Rheum Dis. 2020 Sep 22. doi: 10.1136/annrheumdis-2020-217092.

In a new review, a group of infectious disease experts have summarized and made recommendations about recent findings regarding infections that can occur during treatment with an evolving set of targeted and biologic therapies for rheumatoid arthritis and psoriatic arthritis.

“We claim for the need for multicenter registries and multidisciplinary approaches, for new vaccines trials in RA and PsA, and for better defining when and how biologics can be restarted after severe infections,” lead author Olivier Lortholary, MD, of the Institut Pasteur in Paris, and his coauthors wrote in Annals of the Rheumatic Diseases.

Assessing infection risk related to various inhibitors

Regarding infections caused by TNF-alpha inhibitors (TNFIs), the experts acknowledged a broad increase in risk for mycobacterial and fungal infections, especially tuberculosis and histoplasmosis. They added that patients on TNFIs are more prone to developing pneumonia and soft tissue infections, while smaller studies have indicated a higher risk of listeriosis, legionellosis, herpes zoster (HZ), and reactivation of chronic hepatitis B virus infection.

As for recommendations, they endorsed discontinuing TNFIs when a serious infection occurs and not restarting until after treatment and clinical response. Patients should be screened for latent tuberculosis infection (LTBI) before starting the drug, and anti-TB drugs should be presented to patients with LTBI so they do not progress to active TB.

Regarding other biologics, they cited several studies indicating that IL-6 inhibitors can increase infection risks in RA patients at a rate similar to TNFIs. Among the most common infections were pneumonia and cellulitis. In addition, although PsA patients on IL-17 inhibitors have a dose-dependent risk of mild to moderate mucocutaneous candidiasis, there was no increased risk of serious opportunistic infections like TB.

In assessing JAK inhibitors, they cited a pooled analysis that indicated pneumonia and skin and soft-tissue infections as the most common and noted the high incidence of HZ, compared with other infections. They added that abatacept (Orencia) did not appear to increase risk of infections in RA patients, such as HZ, dermatomycosis, candidiasis, or endemic mycoses. Those same patients did not see an increased overall infection risk after treatment with rituximab (Rituxan), and clinical trials containing treatment with apremilast (Otezla) reported a rare occurrence of serious infections.

Recommendation-wise, they endorsed screening for LTBI before starting IL-6 inhibitors and antiviral prophylaxis with acyclovir in particularly at-risk patients on JAK inhibitors. Age-appropriate influenza vaccinations were also recommended for rituximab, because of the development of rituximab-induced hypogammaglobulinemia.
 

Prediction and prevention

When it comes to predicting infections in patients on biologics, the experts wrote that it “remains a challenge.” The potential effects of pretreatment underlying disease, the lack of validated biomarkers, and the relatively low rate of infections all combine to stymie prediction. That said, they acknowledged ongoing efforts in monitoring lymphocyte subpopulation counts and immunoglobin levels, as well as a clinical score called the RABBIT Risk Score for Infections, which was validated in two separate cohorts.

“As Yogi Berra said, predictions are hard, especially about the future,” Dr. Kavanaugh said. “Discussions with your patient are always important.”

In regard to overall prevention, they acknowledged that most of their recommendations are of low evidence, except for antiviral prophylaxis for hepatitis B patients on rituximab and the aforementioned LTBI therapy in patients on TNFIs. Broadly, they advocated for all RA and PsA patients to receive a full infectious disease evaluation before the start of targeted and biologic therapies.

They also addressed vaccinations, recommending an evaluation of the patient’s immunization history and potentially planning a catch-up schedule for those in need of the influenza vaccine, a diphtheria-tetanus-pertussis booster, or the pneumococcal vaccine. More broadly, they stated that “a better response is expected if [non-live] vaccination is performed before the introduction of immunosuppressive drugs.” They added that live vaccines should be administered as soon as possible.
 

What rheumatologists can do

“So how do you mitigate risk?” Dr. Winthrop asked. “You have to be able to predict the risk, see what’s modifiable, and try to act on it. A lot of the risk of infection has more to do with the patient than the therapy.

“You try to minimize what you’re doing to the patient, particularly around steroids,” he said. “And then you think about screening and vaccinations. Rheumatologists need to be involved in those conversations because they’re the ones who know how these drugs interact with vaccines. A lot of the drugs might dumb down vaccine responses. Be sure to consider that and give the vaccines at times that will optimize their immunogenicity and likely efficacy.”

“Thankfully, infections are not that common,” Dr. Kavanaugh said. “Rheumatologists depend on data from trials, but more safety data comes from registry data and personal and shared experience.”

The authors declared no potential conflicts of interest.

SOURCE: Lortholary O et al. Ann Rheum Dis. 2020 Sep 22. doi: 10.1136/annrheumdis-2020-217092.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

Machine-based learning of genetic and epigenetic characteristics of patients with rheumatoid arthritis could help to predict who is likely to benefit from the biologic drugs adalimumab and etanercept, according to results from a longitudinal, observational cohort study.

In the study, machine learning models created by researchers from Utrecht University in the Netherlands using different parameters predicted true-positive rates for response to adalimumab ranging from 76% to 90% and true-negative rates ranging from 70% to 89%, while for etanercept true-positive rates ranged from about 60% to 80% and true-negative rates ranged from about 82% to 98%.

“These results suggest that we can accurately predict the clinical response before adalimumab and etanercept treatment using molecular signatures-based machine learning models, although the prediction accuracy of these molecular signatures differs between cell types and treatments, underlining the need to study more than one drug, cell type, or epigenetic layers,” first author Weiyang Tao and colleagues wrote in Arthritis & Rheumatology. The ability to predict which tumor necrosis factor inhibitor (TNFi) is the first choice for treatment would be highly beneficial in reducing the time to effective treatment, which has been extensively proven to be a paramount factor for achieving long-sustained disease remission, they noted.

The researchers analyzed gene expression and epigenetic signatures in 80 patients with rheumatoid arthritis prior to treatment with adalimumab or etanercept and then examined patients’ response to treatment at 6 months. They then used that information to build a machine learning model to try to predict treatment response.

Overall, 47.5% of patients were treated with adalimumab, and 52.5% were treated with etanercept. Among the adalimumab group, 53% had a good or moderate response to treatment at 6 months, and among those treated with etanercept, 45% had a good or moderate response.

While there were no differences in baseline clinical parameters between responders and nonresponders, the study found significant genetic and epigenetic differences between patients.

They identified 549 genes that showed significantly different levels of expression between responders and nonresponders treated with adalimumab – in particular, genes involved in DNA and nucleotide binding – and 460 genes that were differentially expressed between etanercept responders and nonresponders, including genes involved in TNF-receptor signaling. However, only 2% of these differentially expressed genes were common in both the adalimumab and etanercept groups, suggesting treatment responses for these two medications have distinct gene signatures.

Looking at DNA methylation, researchers found 16,141 CpG positions – sites of DNA methylation – that were differentially methylated between adalimumab responders and nonresponders, 46% of which were hypermethylated among responders but not nonresponders. In the etanercept group, there were 17,026 differentially methylated sites in responders and nonresponders, 76.3% of which were hypermethylated among responders.

The researchers also noted that among the adalimumab responders, the hypermethylated sites were more likely to be found in the upstream and promoter regions of genes, and on CpG islands.

“Thus, on epigenetic level, we observed a distinct hypermethylation pattern between adalimumab and etanercept responders, suggesting the role of epigenetics in defining response towards adalimumab and to etanercept in PBMCs [peripheral blood mononuclear cells],” the authors wrote.

Given the differences in gene signatures seen in the adalimumab responders and etanercept responders, researchers speculated that different cell types might be involved in the responses to these two treatments. They undertook RNA sequencing on the variety of immune cell types known to be involved in rheumatoid arthritis, which revealed gene-expression differences between adalimumab responders and nonresponders in their CD4+ T cells but not in monocytes. However, the gene-expression differences between etanercept responders and nonresponders were seen in both CD4+ T cells and monocytes.

The study was supported by AbbVie, which manufactures adalimumab, and two authors were supported by the China Scholarship Council and the Netherlands Organization for Scientific Research. No conflicts of interest were declared.

SOURCE: Tao W et al. Arthritis Rheumatol. 2020 Sep 10. doi: 10.1002/art.41516.

Machine-based learning of genetic and epigenetic characteristics of patients with rheumatoid arthritis could help to predict who is likely to benefit from the biologic drugs adalimumab and etanercept, according to results from a longitudinal, observational cohort study.

In the study, machine learning models created by researchers from Utrecht University in the Netherlands using different parameters predicted true-positive rates for response to adalimumab ranging from 76% to 90% and true-negative rates ranging from 70% to 89%, while for etanercept true-positive rates ranged from about 60% to 80% and true-negative rates ranged from about 82% to 98%.

“These results suggest that we can accurately predict the clinical response before adalimumab and etanercept treatment using molecular signatures-based machine learning models, although the prediction accuracy of these molecular signatures differs between cell types and treatments, underlining the need to study more than one drug, cell type, or epigenetic layers,” first author Weiyang Tao and colleagues wrote in Arthritis & Rheumatology. The ability to predict which tumor necrosis factor inhibitor (TNFi) is the first choice for treatment would be highly beneficial in reducing the time to effective treatment, which has been extensively proven to be a paramount factor for achieving long-sustained disease remission, they noted.

The researchers analyzed gene expression and epigenetic signatures in 80 patients with rheumatoid arthritis prior to treatment with adalimumab or etanercept and then examined patients’ response to treatment at 6 months. They then used that information to build a machine learning model to try to predict treatment response.

Overall, 47.5% of patients were treated with adalimumab, and 52.5% were treated with etanercept. Among the adalimumab group, 53% had a good or moderate response to treatment at 6 months, and among those treated with etanercept, 45% had a good or moderate response.

While there were no differences in baseline clinical parameters between responders and nonresponders, the study found significant genetic and epigenetic differences between patients.

They identified 549 genes that showed significantly different levels of expression between responders and nonresponders treated with adalimumab – in particular, genes involved in DNA and nucleotide binding – and 460 genes that were differentially expressed between etanercept responders and nonresponders, including genes involved in TNF-receptor signaling. However, only 2% of these differentially expressed genes were common in both the adalimumab and etanercept groups, suggesting treatment responses for these two medications have distinct gene signatures.

Looking at DNA methylation, researchers found 16,141 CpG positions – sites of DNA methylation – that were differentially methylated between adalimumab responders and nonresponders, 46% of which were hypermethylated among responders but not nonresponders. In the etanercept group, there were 17,026 differentially methylated sites in responders and nonresponders, 76.3% of which were hypermethylated among responders.

The researchers also noted that among the adalimumab responders, the hypermethylated sites were more likely to be found in the upstream and promoter regions of genes, and on CpG islands.

“Thus, on epigenetic level, we observed a distinct hypermethylation pattern between adalimumab and etanercept responders, suggesting the role of epigenetics in defining response towards adalimumab and to etanercept in PBMCs [peripheral blood mononuclear cells],” the authors wrote.

Given the differences in gene signatures seen in the adalimumab responders and etanercept responders, researchers speculated that different cell types might be involved in the responses to these two treatments. They undertook RNA sequencing on the variety of immune cell types known to be involved in rheumatoid arthritis, which revealed gene-expression differences between adalimumab responders and nonresponders in their CD4+ T cells but not in monocytes. However, the gene-expression differences between etanercept responders and nonresponders were seen in both CD4+ T cells and monocytes.

The study was supported by AbbVie, which manufactures adalimumab, and two authors were supported by the China Scholarship Council and the Netherlands Organization for Scientific Research. No conflicts of interest were declared.

SOURCE: Tao W et al. Arthritis Rheumatol. 2020 Sep 10. doi: 10.1002/art.41516.

Machine-based learning of genetic and epigenetic characteristics of patients with rheumatoid arthritis could help to predict who is likely to benefit from the biologic drugs adalimumab and etanercept, according to results from a longitudinal, observational cohort study.

In the study, machine learning models created by researchers from Utrecht University in the Netherlands using different parameters predicted true-positive rates for response to adalimumab ranging from 76% to 90% and true-negative rates ranging from 70% to 89%, while for etanercept true-positive rates ranged from about 60% to 80% and true-negative rates ranged from about 82% to 98%.

“These results suggest that we can accurately predict the clinical response before adalimumab and etanercept treatment using molecular signatures-based machine learning models, although the prediction accuracy of these molecular signatures differs between cell types and treatments, underlining the need to study more than one drug, cell type, or epigenetic layers,” first author Weiyang Tao and colleagues wrote in Arthritis & Rheumatology. The ability to predict which tumor necrosis factor inhibitor (TNFi) is the first choice for treatment would be highly beneficial in reducing the time to effective treatment, which has been extensively proven to be a paramount factor for achieving long-sustained disease remission, they noted.

The researchers analyzed gene expression and epigenetic signatures in 80 patients with rheumatoid arthritis prior to treatment with adalimumab or etanercept and then examined patients’ response to treatment at 6 months. They then used that information to build a machine learning model to try to predict treatment response.

Overall, 47.5% of patients were treated with adalimumab, and 52.5% were treated with etanercept. Among the adalimumab group, 53% had a good or moderate response to treatment at 6 months, and among those treated with etanercept, 45% had a good or moderate response.

While there were no differences in baseline clinical parameters between responders and nonresponders, the study found significant genetic and epigenetic differences between patients.

They identified 549 genes that showed significantly different levels of expression between responders and nonresponders treated with adalimumab – in particular, genes involved in DNA and nucleotide binding – and 460 genes that were differentially expressed between etanercept responders and nonresponders, including genes involved in TNF-receptor signaling. However, only 2% of these differentially expressed genes were common in both the adalimumab and etanercept groups, suggesting treatment responses for these two medications have distinct gene signatures.

Looking at DNA methylation, researchers found 16,141 CpG positions – sites of DNA methylation – that were differentially methylated between adalimumab responders and nonresponders, 46% of which were hypermethylated among responders but not nonresponders. In the etanercept group, there were 17,026 differentially methylated sites in responders and nonresponders, 76.3% of which were hypermethylated among responders.

The researchers also noted that among the adalimumab responders, the hypermethylated sites were more likely to be found in the upstream and promoter regions of genes, and on CpG islands.

“Thus, on epigenetic level, we observed a distinct hypermethylation pattern between adalimumab and etanercept responders, suggesting the role of epigenetics in defining response towards adalimumab and to etanercept in PBMCs [peripheral blood mononuclear cells],” the authors wrote.

Given the differences in gene signatures seen in the adalimumab responders and etanercept responders, researchers speculated that different cell types might be involved in the responses to these two treatments. They undertook RNA sequencing on the variety of immune cell types known to be involved in rheumatoid arthritis, which revealed gene-expression differences between adalimumab responders and nonresponders in their CD4+ T cells but not in monocytes. However, the gene-expression differences between etanercept responders and nonresponders were seen in both CD4+ T cells and monocytes.

The study was supported by AbbVie, which manufactures adalimumab, and two authors were supported by the China Scholarship Council and the Netherlands Organization for Scientific Research. No conflicts of interest were declared.

SOURCE: Tao W et al. Arthritis Rheumatol. 2020 Sep 10. doi: 10.1002/art.41516.

Monitor antidrug antibodies for their impact on drug clearance to maximize treatment outcomes in rheumatology patients treated with biologics, Niels Vande Casteele, PharmD, PhD, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Antidrug antibodies (ADAb) are associated with impaired drug efficacy and safety, he noted. Furthermore, he indicated that when ADAb bind to the drug, they can either block the activity of the drug directly and/or may cause the formation of complexes, leading to accelerated drug clearance and reduced drug exposure.

Dr. Vande Casteele, assistant professor in the department of medicine at the University of California, San Diego, outlined factors that contribute to immunogenicity, which occurs when the body reacts to neoantigens, or when there is a breakdown in immune tolerance, he said.

Genetics can play a key role in the risk for immunogenicity, as can the route of administration, dose, treatment duration, and concomitant diseases or medications, he explained.

In addition, product-related factors including sequence variation, glycosylation, host cells, contaminants and processing impurities, formulation, and handling and storage issues can impact immunogenicity, he noted.

For example, Dr. Vande Casteele cited a study in which the proportion of infliximab-treated patients with positive ADAbs was substantially higher among those receiving the drug intravenously, compared with those receiving it subcutaneously. As for treatment dosing, data on patients treated with infliximab have shown that maintenance therapy is associated with lower rates of immunogenicity, compared to episodic therapy, he said.

In terms of genetics, Dr. Vande Casteele cited a study published in January in Gastroenterology showing the presence of the HLA-DQA1*05 allele, carried by approximately 40% of the European population, significantly increased the rate of immunogenicity to infliximab and adalimumab in patients with Crohn’s disease (hazard ratio, 1.90).
 

Therapeutic drug monitoring and overcoming immunogenicity

Dr. Vande Casteele also reviewed how to measure ADAbs. “Antidrug antibody units and concentrations can differ across assays,” he said.

In clinical practice, “the majority of patients at the time of secondary loss of response will present with low drug exposure, and that is when you measure antidrug antibodies,” he said.

In rheumatology patients, the presence of ADAbs against anti–tumor necrosis factor monoclonal antibodies conveys a risk for treatment discontinuation, as well as “a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases,” Dr. Vande Casteele said.

However, “the combined use of anti–tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks,” he noted.

For therapeutic drug monitoring in patients with a secondary loss of response, “first, look at the trough concentration,” Dr. Vande Casteele said. “If it is optimal, then ADAbs are probably inconsequential.” If the trough is low or undetectable, examine ADAbs, he added. To manage ADAbs, data support the use of drug dose escalation in some cases. However, “you may be able to overcome the antidrug antibodies in some patients with dose escalation, but this is not always a cost-effective strategy in the long term,” and some patients fail a drug despite adequate drug concentration, which may mean they are failing the mechanism, and not because of pharmacokinetic-related issues, he said.

Dr. Vande Casteele cited a post hoc analysis of the TAXIT trial, published in Gastroenterology. It was the first prospective study to look at proactive therapeutic drug monitoring in patients with inflammatory bowel diseases treated with maintenance infliximab. This post hoc analysis showed that ADAbs were overcome with dose escalation in nearly 50% of patients in the lowest two ADAb quartiles at the start of the trial, and although ADAb were masked by dose escalation in the highest two quartiles, measurement with a drug-sensitive assay showed that ADAb never disappeared, he said.

Another strategy to try to overcome immunogenicity is to add an immunomodulator, Dr. Vande Casteele said. He cited a recent study published in Rheumatology showing that the effect of methotrexate was mediated through immunogenicity for immunogenic compounds such as adalimumab.

Importantly, there is a risk for immunogenicity across agents, he noted. “Patients who are antibody positive to the prior anti-TNF are at a higher risk of developing antibodies to subsequent anti-TNFs.”

Dr. Vande Casteele reported receiving research grants from R-Biopharm; grants and personal fees from Takeda and UCB; and personal fees from Alimentiv (formerly Robarts Clinical Trials), Celltrion, and Prometheus. Global Academy for Medical Education and this news organization are owned by the same parent company.

Monitor antidrug antibodies for their impact on drug clearance to maximize treatment outcomes in rheumatology patients treated with biologics, Niels Vande Casteele, PharmD, PhD, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Antidrug antibodies (ADAb) are associated with impaired drug efficacy and safety, he noted. Furthermore, he indicated that when ADAb bind to the drug, they can either block the activity of the drug directly and/or may cause the formation of complexes, leading to accelerated drug clearance and reduced drug exposure.

Dr. Vande Casteele, assistant professor in the department of medicine at the University of California, San Diego, outlined factors that contribute to immunogenicity, which occurs when the body reacts to neoantigens, or when there is a breakdown in immune tolerance, he said.

Genetics can play a key role in the risk for immunogenicity, as can the route of administration, dose, treatment duration, and concomitant diseases or medications, he explained.

In addition, product-related factors including sequence variation, glycosylation, host cells, contaminants and processing impurities, formulation, and handling and storage issues can impact immunogenicity, he noted.

For example, Dr. Vande Casteele cited a study in which the proportion of infliximab-treated patients with positive ADAbs was substantially higher among those receiving the drug intravenously, compared with those receiving it subcutaneously. As for treatment dosing, data on patients treated with infliximab have shown that maintenance therapy is associated with lower rates of immunogenicity, compared to episodic therapy, he said.

In terms of genetics, Dr. Vande Casteele cited a study published in January in Gastroenterology showing the presence of the HLA-DQA1*05 allele, carried by approximately 40% of the European population, significantly increased the rate of immunogenicity to infliximab and adalimumab in patients with Crohn’s disease (hazard ratio, 1.90).
 

Therapeutic drug monitoring and overcoming immunogenicity

Dr. Vande Casteele also reviewed how to measure ADAbs. “Antidrug antibody units and concentrations can differ across assays,” he said.

In clinical practice, “the majority of patients at the time of secondary loss of response will present with low drug exposure, and that is when you measure antidrug antibodies,” he said.

In rheumatology patients, the presence of ADAbs against anti–tumor necrosis factor monoclonal antibodies conveys a risk for treatment discontinuation, as well as “a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases,” Dr. Vande Casteele said.

However, “the combined use of anti–tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks,” he noted.

For therapeutic drug monitoring in patients with a secondary loss of response, “first, look at the trough concentration,” Dr. Vande Casteele said. “If it is optimal, then ADAbs are probably inconsequential.” If the trough is low or undetectable, examine ADAbs, he added. To manage ADAbs, data support the use of drug dose escalation in some cases. However, “you may be able to overcome the antidrug antibodies in some patients with dose escalation, but this is not always a cost-effective strategy in the long term,” and some patients fail a drug despite adequate drug concentration, which may mean they are failing the mechanism, and not because of pharmacokinetic-related issues, he said.

Dr. Vande Casteele cited a post hoc analysis of the TAXIT trial, published in Gastroenterology. It was the first prospective study to look at proactive therapeutic drug monitoring in patients with inflammatory bowel diseases treated with maintenance infliximab. This post hoc analysis showed that ADAbs were overcome with dose escalation in nearly 50% of patients in the lowest two ADAb quartiles at the start of the trial, and although ADAb were masked by dose escalation in the highest two quartiles, measurement with a drug-sensitive assay showed that ADAb never disappeared, he said.

Another strategy to try to overcome immunogenicity is to add an immunomodulator, Dr. Vande Casteele said. He cited a recent study published in Rheumatology showing that the effect of methotrexate was mediated through immunogenicity for immunogenic compounds such as adalimumab.

Importantly, there is a risk for immunogenicity across agents, he noted. “Patients who are antibody positive to the prior anti-TNF are at a higher risk of developing antibodies to subsequent anti-TNFs.”

Dr. Vande Casteele reported receiving research grants from R-Biopharm; grants and personal fees from Takeda and UCB; and personal fees from Alimentiv (formerly Robarts Clinical Trials), Celltrion, and Prometheus. Global Academy for Medical Education and this news organization are owned by the same parent company.

Monitor antidrug antibodies for their impact on drug clearance to maximize treatment outcomes in rheumatology patients treated with biologics, Niels Vande Casteele, PharmD, PhD, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Antidrug antibodies (ADAb) are associated with impaired drug efficacy and safety, he noted. Furthermore, he indicated that when ADAb bind to the drug, they can either block the activity of the drug directly and/or may cause the formation of complexes, leading to accelerated drug clearance and reduced drug exposure.

Dr. Vande Casteele, assistant professor in the department of medicine at the University of California, San Diego, outlined factors that contribute to immunogenicity, which occurs when the body reacts to neoantigens, or when there is a breakdown in immune tolerance, he said.

Genetics can play a key role in the risk for immunogenicity, as can the route of administration, dose, treatment duration, and concomitant diseases or medications, he explained.

In addition, product-related factors including sequence variation, glycosylation, host cells, contaminants and processing impurities, formulation, and handling and storage issues can impact immunogenicity, he noted.

For example, Dr. Vande Casteele cited a study in which the proportion of infliximab-treated patients with positive ADAbs was substantially higher among those receiving the drug intravenously, compared with those receiving it subcutaneously. As for treatment dosing, data on patients treated with infliximab have shown that maintenance therapy is associated with lower rates of immunogenicity, compared to episodic therapy, he said.

In terms of genetics, Dr. Vande Casteele cited a study published in January in Gastroenterology showing the presence of the HLA-DQA1*05 allele, carried by approximately 40% of the European population, significantly increased the rate of immunogenicity to infliximab and adalimumab in patients with Crohn’s disease (hazard ratio, 1.90).
 

Therapeutic drug monitoring and overcoming immunogenicity

Dr. Vande Casteele also reviewed how to measure ADAbs. “Antidrug antibody units and concentrations can differ across assays,” he said.

In clinical practice, “the majority of patients at the time of secondary loss of response will present with low drug exposure, and that is when you measure antidrug antibodies,” he said.

In rheumatology patients, the presence of ADAbs against anti–tumor necrosis factor monoclonal antibodies conveys a risk for treatment discontinuation, as well as “a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases,” Dr. Vande Casteele said.

However, “the combined use of anti–tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks,” he noted.

For therapeutic drug monitoring in patients with a secondary loss of response, “first, look at the trough concentration,” Dr. Vande Casteele said. “If it is optimal, then ADAbs are probably inconsequential.” If the trough is low or undetectable, examine ADAbs, he added. To manage ADAbs, data support the use of drug dose escalation in some cases. However, “you may be able to overcome the antidrug antibodies in some patients with dose escalation, but this is not always a cost-effective strategy in the long term,” and some patients fail a drug despite adequate drug concentration, which may mean they are failing the mechanism, and not because of pharmacokinetic-related issues, he said.

Dr. Vande Casteele cited a post hoc analysis of the TAXIT trial, published in Gastroenterology. It was the first prospective study to look at proactive therapeutic drug monitoring in patients with inflammatory bowel diseases treated with maintenance infliximab. This post hoc analysis showed that ADAbs were overcome with dose escalation in nearly 50% of patients in the lowest two ADAb quartiles at the start of the trial, and although ADAb were masked by dose escalation in the highest two quartiles, measurement with a drug-sensitive assay showed that ADAb never disappeared, he said.

Another strategy to try to overcome immunogenicity is to add an immunomodulator, Dr. Vande Casteele said. He cited a recent study published in Rheumatology showing that the effect of methotrexate was mediated through immunogenicity for immunogenic compounds such as adalimumab.

Importantly, there is a risk for immunogenicity across agents, he noted. “Patients who are antibody positive to the prior anti-TNF are at a higher risk of developing antibodies to subsequent anti-TNFs.”

Dr. Vande Casteele reported receiving research grants from R-Biopharm; grants and personal fees from Takeda and UCB; and personal fees from Alimentiv (formerly Robarts Clinical Trials), Celltrion, and Prometheus. Global Academy for Medical Education and this news organization are owned by the same parent company.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of baricitinib tablets for adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Baricitinib (Olumiant) is already approved in the European Union and the United States to treat moderate to severe active rheumatoid arthritis.

If approved in Europe, it will be the first Janus kinase (JAK) inhibitor and first oral medication indicated to treat patients with AD.

The CHMP’s positive opinion on baricitinib for AD was based on three phase 3, randomized, double-blind, placebo-controlled studies where the JAK inhibitor was used alone or in combination with topical treatments in adults with moderate to severe AD for whom topical treatments were insufficient or not tolerated. In all three studies, baricitinib was shown to be more effective than placebo in achieving skin that is “clear” or “almost clear” at 16 weeks.

“Patients living with AD face difficulties on a daily basis, and this CHMP opinion marks an important milestone in providing adult AD patients with a new potential treatment option,” Thomas Bieber, MD, PhD, professor of dermatology and allergy, University of Bonn (Germany), said in a company news release.

The most common side effects with baricitinib in clinical trials include increased LDL cholesterol, upper respiratory tract infections, and headache.

Patients receiving baricitinib, particularly in combination with immunosuppressants, are at risk of developing serious infections that may lead to hospitalization or death. If a serious infection develops, baricitinib should be stopped until the infection is controlled.

The CHMP’s positive opinion will be sent to the European Commission, which will adopt a final decision regarding an European Union–wide marketing authorization. Once granted, each member state will make decisions about price and reimbursement, taking into account the potential role/use of baricitinib in the context of that country’s national health system.

A version of this story originally appeared on Medscape.com.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of baricitinib tablets for adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Baricitinib (Olumiant) is already approved in the European Union and the United States to treat moderate to severe active rheumatoid arthritis.

If approved in Europe, it will be the first Janus kinase (JAK) inhibitor and first oral medication indicated to treat patients with AD.

The CHMP’s positive opinion on baricitinib for AD was based on three phase 3, randomized, double-blind, placebo-controlled studies where the JAK inhibitor was used alone or in combination with topical treatments in adults with moderate to severe AD for whom topical treatments were insufficient or not tolerated. In all three studies, baricitinib was shown to be more effective than placebo in achieving skin that is “clear” or “almost clear” at 16 weeks.

“Patients living with AD face difficulties on a daily basis, and this CHMP opinion marks an important milestone in providing adult AD patients with a new potential treatment option,” Thomas Bieber, MD, PhD, professor of dermatology and allergy, University of Bonn (Germany), said in a company news release.

The most common side effects with baricitinib in clinical trials include increased LDL cholesterol, upper respiratory tract infections, and headache.

Patients receiving baricitinib, particularly in combination with immunosuppressants, are at risk of developing serious infections that may lead to hospitalization or death. If a serious infection develops, baricitinib should be stopped until the infection is controlled.

The CHMP’s positive opinion will be sent to the European Commission, which will adopt a final decision regarding an European Union–wide marketing authorization. Once granted, each member state will make decisions about price and reimbursement, taking into account the potential role/use of baricitinib in the context of that country’s national health system.

A version of this story originally appeared on Medscape.com.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of baricitinib tablets for adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Baricitinib (Olumiant) is already approved in the European Union and the United States to treat moderate to severe active rheumatoid arthritis.

If approved in Europe, it will be the first Janus kinase (JAK) inhibitor and first oral medication indicated to treat patients with AD.

The CHMP’s positive opinion on baricitinib for AD was based on three phase 3, randomized, double-blind, placebo-controlled studies where the JAK inhibitor was used alone or in combination with topical treatments in adults with moderate to severe AD for whom topical treatments were insufficient or not tolerated. In all three studies, baricitinib was shown to be more effective than placebo in achieving skin that is “clear” or “almost clear” at 16 weeks.

“Patients living with AD face difficulties on a daily basis, and this CHMP opinion marks an important milestone in providing adult AD patients with a new potential treatment option,” Thomas Bieber, MD, PhD, professor of dermatology and allergy, University of Bonn (Germany), said in a company news release.

The most common side effects with baricitinib in clinical trials include increased LDL cholesterol, upper respiratory tract infections, and headache.

Patients receiving baricitinib, particularly in combination with immunosuppressants, are at risk of developing serious infections that may lead to hospitalization or death. If a serious infection develops, baricitinib should be stopped until the infection is controlled.

The CHMP’s positive opinion will be sent to the European Commission, which will adopt a final decision regarding an European Union–wide marketing authorization. Once granted, each member state will make decisions about price and reimbursement, taking into account the potential role/use of baricitinib in the context of that country’s national health system.

A version of this story originally appeared on Medscape.com.

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.