MDedge Rheumatology

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

[email protected]

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

[email protected]

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

[email protected]

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

Febuxostat (Uloric) was not associated with increased cardiovascular risk in patients with gout when compared to those who used allopurinol, in an analysis of new users of the drugs in Medicare fee-for-service claims data from the period of 2008-2016.

The findings, published March 25 in the Journal of the American Heart Association, update and echo the results from a similar previous study by the same Brigham and Women’s Hospital research group that covered 2008-2013 Medicare claims data. That original claims data study from 2018 sought to confirm the findings of the postmarketing surveillance CARES (Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities) trial that led to a boxed warning for increased risk of cardiovascular and all-cause mortality vs. allopurinol. The trial, however, did not show a higher rate of major adverse cardiovascular events (MACE) overall with febuxostat.

The recency of the new data with more febuxostat-exposed patients overall provides greater reassurance on the safety of the drug, corresponding author Seoyoung C. Kim, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, said in an interview. “We also were able to get data on cause of death, which we did not have before when we conducted our first paper.”

Dr. Kim said she was not surprised by any of the findings, which were consistent with the results of her earlier work. “Our result on CV death also was consistent and reassuring,” she noted.

The newest Medicare claims study also corroborates results from FAST (Febuxostat Versus Allopurinol Streamlined Trial), a separate postmarketing surveillance study that was ordered by the European Medicines Agency after febuxostat’s approval in 2009. It showed that the two drugs were noninferior to each other for the risk of all-cause mortality or a composite cardiovascular outcome (hospitalization for nonfatal myocardial infarction, biomarker-positive acute coronary syndrome, nonfatal stroke, or cardiovascular death).

“While CARES showed higher CV death and all-cause death rates in febuxostat compared to allopurinol, FAST did not,” Dr. Kim noted. “Our study of more than 111,000 older gout patients treated with either febuxostat or allopurinol in real-world settings also did not find a difference in the risk of MACE, CV mortality, or all-cause mortality,” she added. “Taking these data all together, I think we can be more certain about the CV safety of febuxostat when its use is clinically indicated or needed,” she said.

Study details

Dr. Kim, first author Ajinkya Pawar, PhD, of Brigham and Women’s, and colleagues identified 467,461 people with gout aged 65 years and older who had been enrolled in Medicare for at least a year. They then used propensity-score matching to compare 27,881 first-time users of febuxostat with 83,643 first-time users of allopurinol on the primary outcome of the incidence of major adverse cardiovascular events (MACE), defined as the first occurrence of myocardial infarction, stroke, or cardiovascular mortality.

In the updated study, the mean follow‐up periods for febuxostat and allopurinol were 284 days and 339 days, respectively. Overall, febuxostat was noninferior to allopurinol with regard to MACE (hazard ratio, 0.99; 95% confidence interval, 0.93-1.05), and the results were consistent among patients with baseline CVD (HR, 0.94). In addition, rates of secondary outcomes of MI, stroke, and cardiovascular mortality were not significantly different between febuxostat and allopurinol patients, except for all-cause mortality (HR, 0.92; 95% CI, 0.87-0.98).

The study findings were limited mainly by the potential bias caused by nonadherence to medications, and potential for residual confounding and misclassification bias, the researchers noted.

However, the study was strengthened by its incident new-user design that allowed only patients with no use of either medication for a year before the first dispensing and its active comparator design, and the data are generalizable to the greater population of older gout patients, they said.

Consequently, the data from this large, real-world study support the safety of febuxostat with regard to cardiovascular risk in gout patients, including those with baseline cardiovascular disease, they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed research grants to Brigham and Women’s Hospital from Roche, Pfizer, AbbVie, and Bristol‐Myers Squibb for unrelated studies. Another author reported serving as the principal investigator with research grants from Vertex, Bayer, and Novartis to Brigham and Women’s Hospital for unrelated projects.

Febuxostat (Uloric) was not associated with increased cardiovascular risk in patients with gout when compared to those who used allopurinol, in an analysis of new users of the drugs in Medicare fee-for-service claims data from the period of 2008-2016.

The findings, published March 25 in the Journal of the American Heart Association, update and echo the results from a similar previous study by the same Brigham and Women’s Hospital research group that covered 2008-2013 Medicare claims data. That original claims data study from 2018 sought to confirm the findings of the postmarketing surveillance CARES (Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities) trial that led to a boxed warning for increased risk of cardiovascular and all-cause mortality vs. allopurinol. The trial, however, did not show a higher rate of major adverse cardiovascular events (MACE) overall with febuxostat.

The recency of the new data with more febuxostat-exposed patients overall provides greater reassurance on the safety of the drug, corresponding author Seoyoung C. Kim, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, said in an interview. “We also were able to get data on cause of death, which we did not have before when we conducted our first paper.”

Dr. Kim said she was not surprised by any of the findings, which were consistent with the results of her earlier work. “Our result on CV death also was consistent and reassuring,” she noted.

The newest Medicare claims study also corroborates results from FAST (Febuxostat Versus Allopurinol Streamlined Trial), a separate postmarketing surveillance study that was ordered by the European Medicines Agency after febuxostat’s approval in 2009. It showed that the two drugs were noninferior to each other for the risk of all-cause mortality or a composite cardiovascular outcome (hospitalization for nonfatal myocardial infarction, biomarker-positive acute coronary syndrome, nonfatal stroke, or cardiovascular death).

“While CARES showed higher CV death and all-cause death rates in febuxostat compared to allopurinol, FAST did not,” Dr. Kim noted. “Our study of more than 111,000 older gout patients treated with either febuxostat or allopurinol in real-world settings also did not find a difference in the risk of MACE, CV mortality, or all-cause mortality,” she added. “Taking these data all together, I think we can be more certain about the CV safety of febuxostat when its use is clinically indicated or needed,” she said.

Study details

Dr. Kim, first author Ajinkya Pawar, PhD, of Brigham and Women’s, and colleagues identified 467,461 people with gout aged 65 years and older who had been enrolled in Medicare for at least a year. They then used propensity-score matching to compare 27,881 first-time users of febuxostat with 83,643 first-time users of allopurinol on the primary outcome of the incidence of major adverse cardiovascular events (MACE), defined as the first occurrence of myocardial infarction, stroke, or cardiovascular mortality.

In the updated study, the mean follow‐up periods for febuxostat and allopurinol were 284 days and 339 days, respectively. Overall, febuxostat was noninferior to allopurinol with regard to MACE (hazard ratio, 0.99; 95% confidence interval, 0.93-1.05), and the results were consistent among patients with baseline CVD (HR, 0.94). In addition, rates of secondary outcomes of MI, stroke, and cardiovascular mortality were not significantly different between febuxostat and allopurinol patients, except for all-cause mortality (HR, 0.92; 95% CI, 0.87-0.98).

The study findings were limited mainly by the potential bias caused by nonadherence to medications, and potential for residual confounding and misclassification bias, the researchers noted.

However, the study was strengthened by its incident new-user design that allowed only patients with no use of either medication for a year before the first dispensing and its active comparator design, and the data are generalizable to the greater population of older gout patients, they said.

Consequently, the data from this large, real-world study support the safety of febuxostat with regard to cardiovascular risk in gout patients, including those with baseline cardiovascular disease, they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed research grants to Brigham and Women’s Hospital from Roche, Pfizer, AbbVie, and Bristol‐Myers Squibb for unrelated studies. Another author reported serving as the principal investigator with research grants from Vertex, Bayer, and Novartis to Brigham and Women’s Hospital for unrelated projects.

Febuxostat (Uloric) was not associated with increased cardiovascular risk in patients with gout when compared to those who used allopurinol, in an analysis of new users of the drugs in Medicare fee-for-service claims data from the period of 2008-2016.

The findings, published March 25 in the Journal of the American Heart Association, update and echo the results from a similar previous study by the same Brigham and Women’s Hospital research group that covered 2008-2013 Medicare claims data. That original claims data study from 2018 sought to confirm the findings of the postmarketing surveillance CARES (Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities) trial that led to a boxed warning for increased risk of cardiovascular and all-cause mortality vs. allopurinol. The trial, however, did not show a higher rate of major adverse cardiovascular events (MACE) overall with febuxostat.

The recency of the new data with more febuxostat-exposed patients overall provides greater reassurance on the safety of the drug, corresponding author Seoyoung C. Kim, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, said in an interview. “We also were able to get data on cause of death, which we did not have before when we conducted our first paper.”

Dr. Kim said she was not surprised by any of the findings, which were consistent with the results of her earlier work. “Our result on CV death also was consistent and reassuring,” she noted.

The newest Medicare claims study also corroborates results from FAST (Febuxostat Versus Allopurinol Streamlined Trial), a separate postmarketing surveillance study that was ordered by the European Medicines Agency after febuxostat’s approval in 2009. It showed that the two drugs were noninferior to each other for the risk of all-cause mortality or a composite cardiovascular outcome (hospitalization for nonfatal myocardial infarction, biomarker-positive acute coronary syndrome, nonfatal stroke, or cardiovascular death).

“While CARES showed higher CV death and all-cause death rates in febuxostat compared to allopurinol, FAST did not,” Dr. Kim noted. “Our study of more than 111,000 older gout patients treated with either febuxostat or allopurinol in real-world settings also did not find a difference in the risk of MACE, CV mortality, or all-cause mortality,” she added. “Taking these data all together, I think we can be more certain about the CV safety of febuxostat when its use is clinically indicated or needed,” she said.

Study details

Dr. Kim, first author Ajinkya Pawar, PhD, of Brigham and Women’s, and colleagues identified 467,461 people with gout aged 65 years and older who had been enrolled in Medicare for at least a year. They then used propensity-score matching to compare 27,881 first-time users of febuxostat with 83,643 first-time users of allopurinol on the primary outcome of the incidence of major adverse cardiovascular events (MACE), defined as the first occurrence of myocardial infarction, stroke, or cardiovascular mortality.

In the updated study, the mean follow‐up periods for febuxostat and allopurinol were 284 days and 339 days, respectively. Overall, febuxostat was noninferior to allopurinol with regard to MACE (hazard ratio, 0.99; 95% confidence interval, 0.93-1.05), and the results were consistent among patients with baseline CVD (HR, 0.94). In addition, rates of secondary outcomes of MI, stroke, and cardiovascular mortality were not significantly different between febuxostat and allopurinol patients, except for all-cause mortality (HR, 0.92; 95% CI, 0.87-0.98).

The study findings were limited mainly by the potential bias caused by nonadherence to medications, and potential for residual confounding and misclassification bias, the researchers noted.

However, the study was strengthened by its incident new-user design that allowed only patients with no use of either medication for a year before the first dispensing and its active comparator design, and the data are generalizable to the greater population of older gout patients, they said.

Consequently, the data from this large, real-world study support the safety of febuxostat with regard to cardiovascular risk in gout patients, including those with baseline cardiovascular disease, they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed research grants to Brigham and Women’s Hospital from Roche, Pfizer, AbbVie, and Bristol‐Myers Squibb for unrelated studies. Another author reported serving as the principal investigator with research grants from Vertex, Bayer, and Novartis to Brigham and Women’s Hospital for unrelated projects.

People experiencing long-term symptoms following acute COVID-19 infection are increasingly meeting criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a phenomenon that highlights the need for unified research and clinical approaches, speakers said at a press briefing March 25 held by the advocacy group MEAction.

“Post-COVID lingering illness was predictable. Similar lingering fatigue syndromes have been reported in the scientific literature for nearly 100 years, following a variety of well-documented infections with viruses, bacteria, fungi, and even protozoa,” said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, Boston.

Core criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for at least 6 months, postexertional malaise (PEM), or a worsening of symptoms following even minor exertion (often described as “crashes”), unrefreshing sleep, and cognitive impairment and/or orthostatic intolerance.

Patients with ME/CFS also commonly experience painful headaches, muscle or joint aches, and allergies/other sensitivities. Although many patients can trace their symptoms to an initiating infection, “the cause is often unclear because the diagnosis is often delayed for months or years after symptom onset,” said Lucinda Bateman, MD, founder of the Bateman Horne Center, Salt Lake City, who leads a clinician coalition that aims to improve ME/CFS management.

In an international survey of 3762 COVID-19 “long-haulers” published in a preprint in December of 2020, the most frequent symptoms reported at least 6 months after illness onset were fatigue in 78%, PEM in 72%, and cognitive dysfunction (“brain fog”) in 55%. At the time of the survey, 45% reported requiring reduced work schedules because of their illness, and 22% reported being unable to work at all.

Dr. Bateman said those findings align with her experience so far with 12 COVID-19 “long haulers” who self-referred to her ME/CFS and fibromyalgia specialty clinic. Nine of the 12 met criteria for postural orthostatic tachycardia syndrome (POTS) based on the 10-minute NASA Lean Test, she said, and half also met the 2016 American College of Rheumatology criteria for fibromyalgia.

“Some were severely impaired. We suspect a small fiber polyneuropathy in about half, and mast cell activation syndrome in more than half. We look forward to doing more testing,” Dr. Bateman said.

To be sure, Dr. Komaroff noted, there are some differences. “Long COVID” patients will often experience breathlessness and ongoing anosmia (loss of taste and smell), which aren’t typical of ME/CFS.

But, he said, “many of the symptoms are quite similar ... My guess is that ME/CFS is an illness with a final common pathway that can be triggered by different things,” said Dr. Komaroff, a senior physician at Brigham and Women’s Hospital in Boston, and editor-in-chief of the Harvard Health Letter.

Based on previous data about CFS suggesting a 10% rate of symptoms persisting at least a year following a variety of infectious agents and the predicted 200 million COVID-19 cases globally by the end of 2021, Dr. Komaroff estimated that about 20 million cases of “long COVID” would be expected in the next year.

‘A huge investment’

On the research side, the National Institutes of Health recently appropriated $1.15 billion dollars over the next 4 years to investigate “the heterogeneity in the recovery process after COVID and to develop treatments for those suffering from [postacute COVID-19 syndrome]” according to a Feb. 5, 2021, blog from the National Institute of Neurological Disorders and Stroke (NINDS).

That same day, another NINDS blog announced “new resources for large-scale ME/CFS research” and emphasized the tie-in with long–COVID-19 syndrome.

“That’s a huge investment. In my opinion, there will be several lingering illnesses following COVID,” Dr. Komaroff said, adding, “It’s my bet that long COVID will prove to be caused by certain kinds of abnormalities in the brain, some of the same abnormalities already identified in ME/CFS. Research will determine whether that’s right or wrong.”

In 2017, NINDS had announced a large increase in funding for ME/CFS research, including the creation of four dedicated research centers. In April 2019, NINDS held a 2-day conference highlighting that ongoing work, as reported by Medscape Medical News.

During the briefing, NINDS clinical director Avindra Nath, MD, described a comprehensive ongoing ME/CFS intramural study he’s been leading since 2016.

He’s now also overseeing two long–COVID-19 studies, one of which has a protocol similar to that of the ME/CFS study and will include individuals who are still experiencing long-term symptoms following confirmed cases of COVID-19. The aim is to screen about 1,300 patients. Several task forces are now examining all of these data together.

“Each aspect is now being analyzed … What we learn from one applies to the other,” Dr. Nath said.  
 

Advice for clinicians

In interviews, Dr. Bateman and Dr. Nath offered clinical advice for managing patients who meet ME/CFS criteria, whether they had confirmed or suspected COVID-19, a different infection, or unknown trigger(s).

Dr. Bateman advised that clinicians assess patients for each of the symptoms individually. “Besides exercise intolerance and PEM, the most commonly missed is orthostatic intolerance. It really doesn’t matter what the cause is, it’s amenable to supportive treatment. It’s one aspect of the illness that contributes to severely impaired function. My plea to all physicians would be for sure to assess for [orthostatic intolerance], and gain an understanding about activity management and avoiding PEM symptoms.”

Dr. Nath noted that an often-challenging situation is when tests for the infectious agent and other blood work come back negative, yet the patient still reports multiple debilitating symptoms. This has been a particular issue with long COVID-19, since many patients became ill early in the pandemic before the polymerase chain reaction (PCR) tests for SARS-CoV-2 were widely available.

“The physician can only order tests that are available at their labs. I think what the physician should do is handle symptoms symptomatically but also refer patients to specialists who are taking care of these patients or to research studies,” he said.

Dr. Bateman added, “Whether they had a documented COVID infection – we just have to let go of that in 2020. Way too many people didn’t have access to a test or the timing wasn’t amenable. If people meet criteria for ME/CFS, it’s irrelevant … It’s mainly a clinical diagnosis. It’s not reliant on identifying the infectious trigger.” 

Dr. Komaroff, who began caring for then-termed “chronic fatigue syndrome” patients and researching the condition more than 30 years ago, said that “every cloud has its silver lining. The increased focus on postinfectious fatigue syndrome is a silver lining in my mind around the terrible dark cloud that is the pandemic of COVID.”

Dr. Komaroff has received personal fees from Serimmune Inc., Ono Pharma, and Deallus, and grants from the NIH. Dr. Bateman is employed by the Bateman Horne Center, which receives grants from the NIH, and fees from Exagen Inc., and Teva Pharmaceutical. Dr. Nath is an NIH employee.

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

People experiencing long-term symptoms following acute COVID-19 infection are increasingly meeting criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a phenomenon that highlights the need for unified research and clinical approaches, speakers said at a press briefing March 25 held by the advocacy group MEAction.

“Post-COVID lingering illness was predictable. Similar lingering fatigue syndromes have been reported in the scientific literature for nearly 100 years, following a variety of well-documented infections with viruses, bacteria, fungi, and even protozoa,” said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, Boston.

Core criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for at least 6 months, postexertional malaise (PEM), or a worsening of symptoms following even minor exertion (often described as “crashes”), unrefreshing sleep, and cognitive impairment and/or orthostatic intolerance.

Patients with ME/CFS also commonly experience painful headaches, muscle or joint aches, and allergies/other sensitivities. Although many patients can trace their symptoms to an initiating infection, “the cause is often unclear because the diagnosis is often delayed for months or years after symptom onset,” said Lucinda Bateman, MD, founder of the Bateman Horne Center, Salt Lake City, who leads a clinician coalition that aims to improve ME/CFS management.

In an international survey of 3762 COVID-19 “long-haulers” published in a preprint in December of 2020, the most frequent symptoms reported at least 6 months after illness onset were fatigue in 78%, PEM in 72%, and cognitive dysfunction (“brain fog”) in 55%. At the time of the survey, 45% reported requiring reduced work schedules because of their illness, and 22% reported being unable to work at all.

Dr. Bateman said those findings align with her experience so far with 12 COVID-19 “long haulers” who self-referred to her ME/CFS and fibromyalgia specialty clinic. Nine of the 12 met criteria for postural orthostatic tachycardia syndrome (POTS) based on the 10-minute NASA Lean Test, she said, and half also met the 2016 American College of Rheumatology criteria for fibromyalgia.

“Some were severely impaired. We suspect a small fiber polyneuropathy in about half, and mast cell activation syndrome in more than half. We look forward to doing more testing,” Dr. Bateman said.

To be sure, Dr. Komaroff noted, there are some differences. “Long COVID” patients will often experience breathlessness and ongoing anosmia (loss of taste and smell), which aren’t typical of ME/CFS.

But, he said, “many of the symptoms are quite similar ... My guess is that ME/CFS is an illness with a final common pathway that can be triggered by different things,” said Dr. Komaroff, a senior physician at Brigham and Women’s Hospital in Boston, and editor-in-chief of the Harvard Health Letter.

Based on previous data about CFS suggesting a 10% rate of symptoms persisting at least a year following a variety of infectious agents and the predicted 200 million COVID-19 cases globally by the end of 2021, Dr. Komaroff estimated that about 20 million cases of “long COVID” would be expected in the next year.

‘A huge investment’

On the research side, the National Institutes of Health recently appropriated $1.15 billion dollars over the next 4 years to investigate “the heterogeneity in the recovery process after COVID and to develop treatments for those suffering from [postacute COVID-19 syndrome]” according to a Feb. 5, 2021, blog from the National Institute of Neurological Disorders and Stroke (NINDS).

That same day, another NINDS blog announced “new resources for large-scale ME/CFS research” and emphasized the tie-in with long–COVID-19 syndrome.

“That’s a huge investment. In my opinion, there will be several lingering illnesses following COVID,” Dr. Komaroff said, adding, “It’s my bet that long COVID will prove to be caused by certain kinds of abnormalities in the brain, some of the same abnormalities already identified in ME/CFS. Research will determine whether that’s right or wrong.”

In 2017, NINDS had announced a large increase in funding for ME/CFS research, including the creation of four dedicated research centers. In April 2019, NINDS held a 2-day conference highlighting that ongoing work, as reported by Medscape Medical News.

During the briefing, NINDS clinical director Avindra Nath, MD, described a comprehensive ongoing ME/CFS intramural study he’s been leading since 2016.

He’s now also overseeing two long–COVID-19 studies, one of which has a protocol similar to that of the ME/CFS study and will include individuals who are still experiencing long-term symptoms following confirmed cases of COVID-19. The aim is to screen about 1,300 patients. Several task forces are now examining all of these data together.

“Each aspect is now being analyzed … What we learn from one applies to the other,” Dr. Nath said.  
 

Advice for clinicians

In interviews, Dr. Bateman and Dr. Nath offered clinical advice for managing patients who meet ME/CFS criteria, whether they had confirmed or suspected COVID-19, a different infection, or unknown trigger(s).

Dr. Bateman advised that clinicians assess patients for each of the symptoms individually. “Besides exercise intolerance and PEM, the most commonly missed is orthostatic intolerance. It really doesn’t matter what the cause is, it’s amenable to supportive treatment. It’s one aspect of the illness that contributes to severely impaired function. My plea to all physicians would be for sure to assess for [orthostatic intolerance], and gain an understanding about activity management and avoiding PEM symptoms.”

Dr. Nath noted that an often-challenging situation is when tests for the infectious agent and other blood work come back negative, yet the patient still reports multiple debilitating symptoms. This has been a particular issue with long COVID-19, since many patients became ill early in the pandemic before the polymerase chain reaction (PCR) tests for SARS-CoV-2 were widely available.

“The physician can only order tests that are available at their labs. I think what the physician should do is handle symptoms symptomatically but also refer patients to specialists who are taking care of these patients or to research studies,” he said.

Dr. Bateman added, “Whether they had a documented COVID infection – we just have to let go of that in 2020. Way too many people didn’t have access to a test or the timing wasn’t amenable. If people meet criteria for ME/CFS, it’s irrelevant … It’s mainly a clinical diagnosis. It’s not reliant on identifying the infectious trigger.” 

Dr. Komaroff, who began caring for then-termed “chronic fatigue syndrome” patients and researching the condition more than 30 years ago, said that “every cloud has its silver lining. The increased focus on postinfectious fatigue syndrome is a silver lining in my mind around the terrible dark cloud that is the pandemic of COVID.”

Dr. Komaroff has received personal fees from Serimmune Inc., Ono Pharma, and Deallus, and grants from the NIH. Dr. Bateman is employed by the Bateman Horne Center, which receives grants from the NIH, and fees from Exagen Inc., and Teva Pharmaceutical. Dr. Nath is an NIH employee.

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

People experiencing long-term symptoms following acute COVID-19 infection are increasingly meeting criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a phenomenon that highlights the need for unified research and clinical approaches, speakers said at a press briefing March 25 held by the advocacy group MEAction.

“Post-COVID lingering illness was predictable. Similar lingering fatigue syndromes have been reported in the scientific literature for nearly 100 years, following a variety of well-documented infections with viruses, bacteria, fungi, and even protozoa,” said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, Boston.

Core criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for at least 6 months, postexertional malaise (PEM), or a worsening of symptoms following even minor exertion (often described as “crashes”), unrefreshing sleep, and cognitive impairment and/or orthostatic intolerance.

Patients with ME/CFS also commonly experience painful headaches, muscle or joint aches, and allergies/other sensitivities. Although many patients can trace their symptoms to an initiating infection, “the cause is often unclear because the diagnosis is often delayed for months or years after symptom onset,” said Lucinda Bateman, MD, founder of the Bateman Horne Center, Salt Lake City, who leads a clinician coalition that aims to improve ME/CFS management.

In an international survey of 3762 COVID-19 “long-haulers” published in a preprint in December of 2020, the most frequent symptoms reported at least 6 months after illness onset were fatigue in 78%, PEM in 72%, and cognitive dysfunction (“brain fog”) in 55%. At the time of the survey, 45% reported requiring reduced work schedules because of their illness, and 22% reported being unable to work at all.

Dr. Bateman said those findings align with her experience so far with 12 COVID-19 “long haulers” who self-referred to her ME/CFS and fibromyalgia specialty clinic. Nine of the 12 met criteria for postural orthostatic tachycardia syndrome (POTS) based on the 10-minute NASA Lean Test, she said, and half also met the 2016 American College of Rheumatology criteria for fibromyalgia.

“Some were severely impaired. We suspect a small fiber polyneuropathy in about half, and mast cell activation syndrome in more than half. We look forward to doing more testing,” Dr. Bateman said.

To be sure, Dr. Komaroff noted, there are some differences. “Long COVID” patients will often experience breathlessness and ongoing anosmia (loss of taste and smell), which aren’t typical of ME/CFS.

But, he said, “many of the symptoms are quite similar ... My guess is that ME/CFS is an illness with a final common pathway that can be triggered by different things,” said Dr. Komaroff, a senior physician at Brigham and Women’s Hospital in Boston, and editor-in-chief of the Harvard Health Letter.

Based on previous data about CFS suggesting a 10% rate of symptoms persisting at least a year following a variety of infectious agents and the predicted 200 million COVID-19 cases globally by the end of 2021, Dr. Komaroff estimated that about 20 million cases of “long COVID” would be expected in the next year.

‘A huge investment’

On the research side, the National Institutes of Health recently appropriated $1.15 billion dollars over the next 4 years to investigate “the heterogeneity in the recovery process after COVID and to develop treatments for those suffering from [postacute COVID-19 syndrome]” according to a Feb. 5, 2021, blog from the National Institute of Neurological Disorders and Stroke (NINDS).

That same day, another NINDS blog announced “new resources for large-scale ME/CFS research” and emphasized the tie-in with long–COVID-19 syndrome.

“That’s a huge investment. In my opinion, there will be several lingering illnesses following COVID,” Dr. Komaroff said, adding, “It’s my bet that long COVID will prove to be caused by certain kinds of abnormalities in the brain, some of the same abnormalities already identified in ME/CFS. Research will determine whether that’s right or wrong.”

In 2017, NINDS had announced a large increase in funding for ME/CFS research, including the creation of four dedicated research centers. In April 2019, NINDS held a 2-day conference highlighting that ongoing work, as reported by Medscape Medical News.

During the briefing, NINDS clinical director Avindra Nath, MD, described a comprehensive ongoing ME/CFS intramural study he’s been leading since 2016.

He’s now also overseeing two long–COVID-19 studies, one of which has a protocol similar to that of the ME/CFS study and will include individuals who are still experiencing long-term symptoms following confirmed cases of COVID-19. The aim is to screen about 1,300 patients. Several task forces are now examining all of these data together.

“Each aspect is now being analyzed … What we learn from one applies to the other,” Dr. Nath said.  
 

Advice for clinicians

In interviews, Dr. Bateman and Dr. Nath offered clinical advice for managing patients who meet ME/CFS criteria, whether they had confirmed or suspected COVID-19, a different infection, or unknown trigger(s).

Dr. Bateman advised that clinicians assess patients for each of the symptoms individually. “Besides exercise intolerance and PEM, the most commonly missed is orthostatic intolerance. It really doesn’t matter what the cause is, it’s amenable to supportive treatment. It’s one aspect of the illness that contributes to severely impaired function. My plea to all physicians would be for sure to assess for [orthostatic intolerance], and gain an understanding about activity management and avoiding PEM symptoms.”

Dr. Nath noted that an often-challenging situation is when tests for the infectious agent and other blood work come back negative, yet the patient still reports multiple debilitating symptoms. This has been a particular issue with long COVID-19, since many patients became ill early in the pandemic before the polymerase chain reaction (PCR) tests for SARS-CoV-2 were widely available.

“The physician can only order tests that are available at their labs. I think what the physician should do is handle symptoms symptomatically but also refer patients to specialists who are taking care of these patients or to research studies,” he said.

Dr. Bateman added, “Whether they had a documented COVID infection – we just have to let go of that in 2020. Way too many people didn’t have access to a test or the timing wasn’t amenable. If people meet criteria for ME/CFS, it’s irrelevant … It’s mainly a clinical diagnosis. It’s not reliant on identifying the infectious trigger.” 

Dr. Komaroff, who began caring for then-termed “chronic fatigue syndrome” patients and researching the condition more than 30 years ago, said that “every cloud has its silver lining. The increased focus on postinfectious fatigue syndrome is a silver lining in my mind around the terrible dark cloud that is the pandemic of COVID.”

Dr. Komaroff has received personal fees from Serimmune Inc., Ono Pharma, and Deallus, and grants from the NIH. Dr. Bateman is employed by the Bateman Horne Center, which receives grants from the NIH, and fees from Exagen Inc., and Teva Pharmaceutical. Dr. Nath is an NIH employee.

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

Every day Melissa Fulton, RN, MSN, FNP, APRN-C, shows up to work, she’s ready for another fight. An advanced practice nurse who specializes in multiple sclerosis care, Ms. Fulton said she typically spends more than a third of her time battling it out with insurance companies over drugs she knows her patients need but that insurers don’t want to cover. Instead, they want the patient to first receive less expensive and often less efficacious drugs, even if that goes against recommendations and, in some cases, against the patient’s medical history.

The maddening protocol – familiar to health care providers everywhere – is known as “step therapy.” It forces patients to try alternative medications – medications that often fail – before receiving the one initially prescribed. The process can take weeks or months, which is time that some patients don’t have. Step therapy was sold as a way to lower costs. However, beyond the ethically problematic notion of forcing sick patients to receiver cheaper alternatives that are ineffective, research has also shown it may actually be more costly in the long run.

Ms. Fulton, who works at Saunders Medical Center in Wahoo, Neb., is a veteran in the war against step therapy. She is used to pushing her appeals up the insurance company chain of command, past nonmedical reviewers, until her patient’s case finally lands on the desk of someone with a neurology background. She said that can take three or four appeals – a judge might even get involved – and the patient could still lose. “This happens constantly,” she said, “but we fight like hell.”

Fortunately, life may soon get a little easier for Ms. Fulton. In late March, a bill to restrict step therapy made it through the Nebraska state legislature and is on its way to the governor’s desk. The Step Therapy Reform Act doesn’t outright ban the practice; however, it will put guardrails in place. It requires that insurers respond to appeals within certain time frames, and it creates key exemptions.

When the governor signs off, Nebraska will join more than two dozen other states that already have step therapy restrictions on the books, according to Hannah Lynch, MPS, associate director of federal government relations and health policy at the National Psoriasis Foundation, a leading advocate to reform and protect against the insurance practice. “There’s a lot of frustration out there,” Ms. Lynch said. “It really hinders providers’ ability to make decisions they think will have the best outcomes.”

Driven by coalitions of doctors, nurses, and patients, laws reining in step therapy have been adopted at a relatively quick clip, mostly within the past 5 years. Recent additions include South Dakota and North Carolina, which adopted step therapy laws in 2020, and Arkansas, which passed a law earlier this year.

Ms. Lynch attributed growing support to rising out-of-pocket drug costs and the introduction of biologic drugs, which are often more effective but also more expensive. Like Nebraska’s law, most step therapy reform legislation carves out exemptions and requires timely appeals processes; however, many of the laws still have significant gaps, such as not including certain types of insurance plans.

Ideally, Ms. Lynch said, the protections would apply to all types of health plans that are regulated at the state level, such as Medicaid, state employee health plans, and coverage sold through state insurance exchanges. Closing loopholes in the laws is a top priority for advocates, she added, pointing to work currently underway in Arkansas to extend its new protections to Medicaid expansion patients.

“With so many outside stakeholders, you have to compromise – it’s a give and take,” Ms. Lynch said. Still, when it comes to fighting step therapy, she says, “Any protection on the books is always our first goal when we go into a state.”

Putting patients first

Lisa Arkin, MD, a pediatric dermatologist at the University of Wisconsin–Madison, said she finds herself “swimming upstream every day in the fight with insurance.” Her patients are typically on their second or third stop and have more complex disorders. Dr. Arkin said that the problem with step therapy is that it tries to squeeze all patients into the same box, even if the circumstances don’t fit.

Her state passed restrictions on step therapy in 2019, but the measures only went into effect last year. Under the Wisconsin law, patients can be granted an exemption if an alternative treatment is contraindicated, likely to cause harm, or expected to be ineffective. Patients can also be exempt if their current treatment is working.

Dr. Arkin, an outspoken advocate for curbing step therapy, says the Wisconsin law is “very strong.” However, because it only applies to certain health plans – state employee health plans and those purchased in the state’s health insurance exchange – fewer than half the state’s patients benefit from its protections. She notes that some of the most severe presentations she treats occur in patients who rely on Medicaid coverage and already face barriers to care.

“I’m a doctor who puts up a fuss [with insurers], but that’s not fair – we shouldn’t have to do that,” Dr. Arkin said. “To me, it’s really critical to make this an even playing field so this law affords protection to everyone I see in the clinic.”

Major medical associations caution against step therapy as well. The American Society of Clinical Oncology and the American Medical Association have called out the risks to patient safety and health. In fact, in 2019, after the Centers for Medicare & Medicaid Services gave new authority to Medicare Advantage plans to start using step therapy, dozens of national medical groups called out the agency for allowing a practice that could potentially hurt patients and undercut the physician-patient decision-making process.

Last year, in a new position paper from the American College of Physicians, authors laid out recommendations for combating step therapy’s side effects. These recommendations included making related data transparent to the public and minimizing the policy’s disruptions to care. Jacqueline W. Fincher, MD, MACP, a member of the committee that issued the position paper and who is a primary care physician in Georgia, said such insurance practices need to be designed with “strong input from frontline physicians, not clipboard physicians.

“What we want from insurers is understanding, transparency, and the least burdensome protocol to provide patients the care they need at a cost-effective price they can afford,” said Dr. Fincher, who is also the current president of the ACP. “The focus needs to be on what’s in the patient’s best interest.”
 

Every year a new fight

“We all dread January,” said Dr. Fincher. That is the worst month, she added, because new health benefits go into effect, which means patients who are responding well to certain treatments may suddenly face new restrictions.

Another aggravating aspect of step therapy? It is often difficult – if not impossible – to access information on specific step therapy protocols in a patient’s health plan in real time in the exam room, where treatment conversations actually take place. In a more patient-centered world, Dr. Fincher said, she would be able to use the electronic health record system to quickly identify whether a patient’s plan covers a particular treatment and, if not, what the alternatives are.

Georgia’s new step therapy law went into effect last year. Like laws in other states, it spells out step therapy exemptions and sets time frames in which insurers must respond to exceptions and appeals. Dr. Fincher, who spoke in favor of the new law, said she’s “happy for any step forward.” Still, the growing burden of prior authorization rules are an utter “time sink” for her and her staff.

“I have to justify my decisions to nondoctors before I even get to a doctor, and that’s really frustrating,” she said. “We’re talking about people here, not widgets.”

Advocates in Nevada are hoping this is the year a step therapy bill will make it into law in their state. As of March, one had yet to be introduced in the state legislature. Tom McCoy, director of state government affairs at the Nevada Chronic Care Collaborative, said existing Nevada law already prohibits nonmedical drug switching during a policy year; however, insurers can still make changes the following year.

A bill to rein in step therapy was proposed previously, Mr. McCoy said, but it never got off the ground. The collaborative, as well as about two dozen organizations representing Nevada providers and patients, are now calling on state lawmakers to make the issue a priority in the current session.

“The health plans have a lot of power – a lot,” Mr. McCoy said. “We’re hoping to get a [legislative] sponsor in 2021 ... but it’s also been a really hard year to connect legislators with patients and doctors, and being able to hear their stories really does make a difference.”

In Nebraska, Marcus Snow, MD, a rheumatologist at Nebraska Medicine, in Omaha, said that the state’s new step therapy law will be a “great first step in helping to provide some guardrails” around the practice. He noted that turnaround requirements for insurer responses are “sorely needed.” However, he said that, because the bill doesn’t apply to all health plans, many Nebraskans still won’t benefit.

Dealing with step therapy is a daily “headache” for Dr. Snow, who says navigating the bureaucracy of prior authorization seems to be getting worse every year. Like his peers around the country, he spends an inordinate amount of time pushing appeals up the insurance company ranks to get access to treatments he believes will be most effective. But Snow says that, more than just being a mountain of tiresome red tape, these practices also intrude on the patient-provider relationship, casting an unsettling sense of uncertainty that the ultimate decision about the best course of action isn’t up to the doctor and patient at all.

“In the end, the insurance company is the judge and jury of my prescription,” Dr. Snow said. “They’d argue I can still prescribe it, but if it costs $70,000 a year – I don’t know who can afford that.”

Ms. Lynch, at the National Psoriasis Foundation, said their step therapy advocacy will continue to take a two-pronged approach. They will push for new and expanded protections at both state and federal levels. Protections are needed at both levels to make sure that all health plans regulated by all entities are covered. In the U.S. Senate and the House, step therapy bills were reintroduced this year. They would apply to health plans subject to the federal Employee Retirement Income Security Act, which governs employer-sponsored health coverage, and could close a big gap in existing protections. Oregon, New Jersey, and Arizona are at the top of the foundation’s advocacy list this year, according to Ms. Lynch.

“Folks are really starting to pay more attention to this issue,” she said. “And hearing those real-world stories and frustrations is definitely one of the most effective tools we have.”

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

Every day Melissa Fulton, RN, MSN, FNP, APRN-C, shows up to work, she’s ready for another fight. An advanced practice nurse who specializes in multiple sclerosis care, Ms. Fulton said she typically spends more than a third of her time battling it out with insurance companies over drugs she knows her patients need but that insurers don’t want to cover. Instead, they want the patient to first receive less expensive and often less efficacious drugs, even if that goes against recommendations and, in some cases, against the patient’s medical history.

The maddening protocol – familiar to health care providers everywhere – is known as “step therapy.” It forces patients to try alternative medications – medications that often fail – before receiving the one initially prescribed. The process can take weeks or months, which is time that some patients don’t have. Step therapy was sold as a way to lower costs. However, beyond the ethically problematic notion of forcing sick patients to receiver cheaper alternatives that are ineffective, research has also shown it may actually be more costly in the long run.

Ms. Fulton, who works at Saunders Medical Center in Wahoo, Neb., is a veteran in the war against step therapy. She is used to pushing her appeals up the insurance company chain of command, past nonmedical reviewers, until her patient’s case finally lands on the desk of someone with a neurology background. She said that can take three or four appeals – a judge might even get involved – and the patient could still lose. “This happens constantly,” she said, “but we fight like hell.”

Fortunately, life may soon get a little easier for Ms. Fulton. In late March, a bill to restrict step therapy made it through the Nebraska state legislature and is on its way to the governor’s desk. The Step Therapy Reform Act doesn’t outright ban the practice; however, it will put guardrails in place. It requires that insurers respond to appeals within certain time frames, and it creates key exemptions.

When the governor signs off, Nebraska will join more than two dozen other states that already have step therapy restrictions on the books, according to Hannah Lynch, MPS, associate director of federal government relations and health policy at the National Psoriasis Foundation, a leading advocate to reform and protect against the insurance practice. “There’s a lot of frustration out there,” Ms. Lynch said. “It really hinders providers’ ability to make decisions they think will have the best outcomes.”

Driven by coalitions of doctors, nurses, and patients, laws reining in step therapy have been adopted at a relatively quick clip, mostly within the past 5 years. Recent additions include South Dakota and North Carolina, which adopted step therapy laws in 2020, and Arkansas, which passed a law earlier this year.

Ms. Lynch attributed growing support to rising out-of-pocket drug costs and the introduction of biologic drugs, which are often more effective but also more expensive. Like Nebraska’s law, most step therapy reform legislation carves out exemptions and requires timely appeals processes; however, many of the laws still have significant gaps, such as not including certain types of insurance plans.

Ideally, Ms. Lynch said, the protections would apply to all types of health plans that are regulated at the state level, such as Medicaid, state employee health plans, and coverage sold through state insurance exchanges. Closing loopholes in the laws is a top priority for advocates, she added, pointing to work currently underway in Arkansas to extend its new protections to Medicaid expansion patients.

“With so many outside stakeholders, you have to compromise – it’s a give and take,” Ms. Lynch said. Still, when it comes to fighting step therapy, she says, “Any protection on the books is always our first goal when we go into a state.”

Putting patients first

Lisa Arkin, MD, a pediatric dermatologist at the University of Wisconsin–Madison, said she finds herself “swimming upstream every day in the fight with insurance.” Her patients are typically on their second or third stop and have more complex disorders. Dr. Arkin said that the problem with step therapy is that it tries to squeeze all patients into the same box, even if the circumstances don’t fit.

Her state passed restrictions on step therapy in 2019, but the measures only went into effect last year. Under the Wisconsin law, patients can be granted an exemption if an alternative treatment is contraindicated, likely to cause harm, or expected to be ineffective. Patients can also be exempt if their current treatment is working.

Dr. Arkin, an outspoken advocate for curbing step therapy, says the Wisconsin law is “very strong.” However, because it only applies to certain health plans – state employee health plans and those purchased in the state’s health insurance exchange – fewer than half the state’s patients benefit from its protections. She notes that some of the most severe presentations she treats occur in patients who rely on Medicaid coverage and already face barriers to care.

“I’m a doctor who puts up a fuss [with insurers], but that’s not fair – we shouldn’t have to do that,” Dr. Arkin said. “To me, it’s really critical to make this an even playing field so this law affords protection to everyone I see in the clinic.”

Major medical associations caution against step therapy as well. The American Society of Clinical Oncology and the American Medical Association have called out the risks to patient safety and health. In fact, in 2019, after the Centers for Medicare & Medicaid Services gave new authority to Medicare Advantage plans to start using step therapy, dozens of national medical groups called out the agency for allowing a practice that could potentially hurt patients and undercut the physician-patient decision-making process.

Last year, in a new position paper from the American College of Physicians, authors laid out recommendations for combating step therapy’s side effects. These recommendations included making related data transparent to the public and minimizing the policy’s disruptions to care. Jacqueline W. Fincher, MD, MACP, a member of the committee that issued the position paper and who is a primary care physician in Georgia, said such insurance practices need to be designed with “strong input from frontline physicians, not clipboard physicians.

“What we want from insurers is understanding, transparency, and the least burdensome protocol to provide patients the care they need at a cost-effective price they can afford,” said Dr. Fincher, who is also the current president of the ACP. “The focus needs to be on what’s in the patient’s best interest.”
 

Every year a new fight

“We all dread January,” said Dr. Fincher. That is the worst month, she added, because new health benefits go into effect, which means patients who are responding well to certain treatments may suddenly face new restrictions.

Another aggravating aspect of step therapy? It is often difficult – if not impossible – to access information on specific step therapy protocols in a patient’s health plan in real time in the exam room, where treatment conversations actually take place. In a more patient-centered world, Dr. Fincher said, she would be able to use the electronic health record system to quickly identify whether a patient’s plan covers a particular treatment and, if not, what the alternatives are.

Georgia’s new step therapy law went into effect last year. Like laws in other states, it spells out step therapy exemptions and sets time frames in which insurers must respond to exceptions and appeals. Dr. Fincher, who spoke in favor of the new law, said she’s “happy for any step forward.” Still, the growing burden of prior authorization rules are an utter “time sink” for her and her staff.

“I have to justify my decisions to nondoctors before I even get to a doctor, and that’s really frustrating,” she said. “We’re talking about people here, not widgets.”

Advocates in Nevada are hoping this is the year a step therapy bill will make it into law in their state. As of March, one had yet to be introduced in the state legislature. Tom McCoy, director of state government affairs at the Nevada Chronic Care Collaborative, said existing Nevada law already prohibits nonmedical drug switching during a policy year; however, insurers can still make changes the following year.

A bill to rein in step therapy was proposed previously, Mr. McCoy said, but it never got off the ground. The collaborative, as well as about two dozen organizations representing Nevada providers and patients, are now calling on state lawmakers to make the issue a priority in the current session.

“The health plans have a lot of power – a lot,” Mr. McCoy said. “We’re hoping to get a [legislative] sponsor in 2021 ... but it’s also been a really hard year to connect legislators with patients and doctors, and being able to hear their stories really does make a difference.”

In Nebraska, Marcus Snow, MD, a rheumatologist at Nebraska Medicine, in Omaha, said that the state’s new step therapy law will be a “great first step in helping to provide some guardrails” around the practice. He noted that turnaround requirements for insurer responses are “sorely needed.” However, he said that, because the bill doesn’t apply to all health plans, many Nebraskans still won’t benefit.

Dealing with step therapy is a daily “headache” for Dr. Snow, who says navigating the bureaucracy of prior authorization seems to be getting worse every year. Like his peers around the country, he spends an inordinate amount of time pushing appeals up the insurance company ranks to get access to treatments he believes will be most effective. But Snow says that, more than just being a mountain of tiresome red tape, these practices also intrude on the patient-provider relationship, casting an unsettling sense of uncertainty that the ultimate decision about the best course of action isn’t up to the doctor and patient at all.

“In the end, the insurance company is the judge and jury of my prescription,” Dr. Snow said. “They’d argue I can still prescribe it, but if it costs $70,000 a year – I don’t know who can afford that.”

Ms. Lynch, at the National Psoriasis Foundation, said their step therapy advocacy will continue to take a two-pronged approach. They will push for new and expanded protections at both state and federal levels. Protections are needed at both levels to make sure that all health plans regulated by all entities are covered. In the U.S. Senate and the House, step therapy bills were reintroduced this year. They would apply to health plans subject to the federal Employee Retirement Income Security Act, which governs employer-sponsored health coverage, and could close a big gap in existing protections. Oregon, New Jersey, and Arizona are at the top of the foundation’s advocacy list this year, according to Ms. Lynch.

“Folks are really starting to pay more attention to this issue,” she said. “And hearing those real-world stories and frustrations is definitely one of the most effective tools we have.”

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

Every day Melissa Fulton, RN, MSN, FNP, APRN-C, shows up to work, she’s ready for another fight. An advanced practice nurse who specializes in multiple sclerosis care, Ms. Fulton said she typically spends more than a third of her time battling it out with insurance companies over drugs she knows her patients need but that insurers don’t want to cover. Instead, they want the patient to first receive less expensive and often less efficacious drugs, even if that goes against recommendations and, in some cases, against the patient’s medical history.

The maddening protocol – familiar to health care providers everywhere – is known as “step therapy.” It forces patients to try alternative medications – medications that often fail – before receiving the one initially prescribed. The process can take weeks or months, which is time that some patients don’t have. Step therapy was sold as a way to lower costs. However, beyond the ethically problematic notion of forcing sick patients to receiver cheaper alternatives that are ineffective, research has also shown it may actually be more costly in the long run.

Ms. Fulton, who works at Saunders Medical Center in Wahoo, Neb., is a veteran in the war against step therapy. She is used to pushing her appeals up the insurance company chain of command, past nonmedical reviewers, until her patient’s case finally lands on the desk of someone with a neurology background. She said that can take three or four appeals – a judge might even get involved – and the patient could still lose. “This happens constantly,” she said, “but we fight like hell.”

Fortunately, life may soon get a little easier for Ms. Fulton. In late March, a bill to restrict step therapy made it through the Nebraska state legislature and is on its way to the governor’s desk. The Step Therapy Reform Act doesn’t outright ban the practice; however, it will put guardrails in place. It requires that insurers respond to appeals within certain time frames, and it creates key exemptions.

When the governor signs off, Nebraska will join more than two dozen other states that already have step therapy restrictions on the books, according to Hannah Lynch, MPS, associate director of federal government relations and health policy at the National Psoriasis Foundation, a leading advocate to reform and protect against the insurance practice. “There’s a lot of frustration out there,” Ms. Lynch said. “It really hinders providers’ ability to make decisions they think will have the best outcomes.”

Driven by coalitions of doctors, nurses, and patients, laws reining in step therapy have been adopted at a relatively quick clip, mostly within the past 5 years. Recent additions include South Dakota and North Carolina, which adopted step therapy laws in 2020, and Arkansas, which passed a law earlier this year.

Ms. Lynch attributed growing support to rising out-of-pocket drug costs and the introduction of biologic drugs, which are often more effective but also more expensive. Like Nebraska’s law, most step therapy reform legislation carves out exemptions and requires timely appeals processes; however, many of the laws still have significant gaps, such as not including certain types of insurance plans.

Ideally, Ms. Lynch said, the protections would apply to all types of health plans that are regulated at the state level, such as Medicaid, state employee health plans, and coverage sold through state insurance exchanges. Closing loopholes in the laws is a top priority for advocates, she added, pointing to work currently underway in Arkansas to extend its new protections to Medicaid expansion patients.

“With so many outside stakeholders, you have to compromise – it’s a give and take,” Ms. Lynch said. Still, when it comes to fighting step therapy, she says, “Any protection on the books is always our first goal when we go into a state.”

Putting patients first

Lisa Arkin, MD, a pediatric dermatologist at the University of Wisconsin–Madison, said she finds herself “swimming upstream every day in the fight with insurance.” Her patients are typically on their second or third stop and have more complex disorders. Dr. Arkin said that the problem with step therapy is that it tries to squeeze all patients into the same box, even if the circumstances don’t fit.

Her state passed restrictions on step therapy in 2019, but the measures only went into effect last year. Under the Wisconsin law, patients can be granted an exemption if an alternative treatment is contraindicated, likely to cause harm, or expected to be ineffective. Patients can also be exempt if their current treatment is working.

Dr. Arkin, an outspoken advocate for curbing step therapy, says the Wisconsin law is “very strong.” However, because it only applies to certain health plans – state employee health plans and those purchased in the state’s health insurance exchange – fewer than half the state’s patients benefit from its protections. She notes that some of the most severe presentations she treats occur in patients who rely on Medicaid coverage and already face barriers to care.

“I’m a doctor who puts up a fuss [with insurers], but that’s not fair – we shouldn’t have to do that,” Dr. Arkin said. “To me, it’s really critical to make this an even playing field so this law affords protection to everyone I see in the clinic.”

Major medical associations caution against step therapy as well. The American Society of Clinical Oncology and the American Medical Association have called out the risks to patient safety and health. In fact, in 2019, after the Centers for Medicare & Medicaid Services gave new authority to Medicare Advantage plans to start using step therapy, dozens of national medical groups called out the agency for allowing a practice that could potentially hurt patients and undercut the physician-patient decision-making process.

Last year, in a new position paper from the American College of Physicians, authors laid out recommendations for combating step therapy’s side effects. These recommendations included making related data transparent to the public and minimizing the policy’s disruptions to care. Jacqueline W. Fincher, MD, MACP, a member of the committee that issued the position paper and who is a primary care physician in Georgia, said such insurance practices need to be designed with “strong input from frontline physicians, not clipboard physicians.

“What we want from insurers is understanding, transparency, and the least burdensome protocol to provide patients the care they need at a cost-effective price they can afford,” said Dr. Fincher, who is also the current president of the ACP. “The focus needs to be on what’s in the patient’s best interest.”
 

Every year a new fight

“We all dread January,” said Dr. Fincher. That is the worst month, she added, because new health benefits go into effect, which means patients who are responding well to certain treatments may suddenly face new restrictions.

Another aggravating aspect of step therapy? It is often difficult – if not impossible – to access information on specific step therapy protocols in a patient’s health plan in real time in the exam room, where treatment conversations actually take place. In a more patient-centered world, Dr. Fincher said, she would be able to use the electronic health record system to quickly identify whether a patient’s plan covers a particular treatment and, if not, what the alternatives are.

Georgia’s new step therapy law went into effect last year. Like laws in other states, it spells out step therapy exemptions and sets time frames in which insurers must respond to exceptions and appeals. Dr. Fincher, who spoke in favor of the new law, said she’s “happy for any step forward.” Still, the growing burden of prior authorization rules are an utter “time sink” for her and her staff.

“I have to justify my decisions to nondoctors before I even get to a doctor, and that’s really frustrating,” she said. “We’re talking about people here, not widgets.”

Advocates in Nevada are hoping this is the year a step therapy bill will make it into law in their state. As of March, one had yet to be introduced in the state legislature. Tom McCoy, director of state government affairs at the Nevada Chronic Care Collaborative, said existing Nevada law already prohibits nonmedical drug switching during a policy year; however, insurers can still make changes the following year.

A bill to rein in step therapy was proposed previously, Mr. McCoy said, but it never got off the ground. The collaborative, as well as about two dozen organizations representing Nevada providers and patients, are now calling on state lawmakers to make the issue a priority in the current session.

“The health plans have a lot of power – a lot,” Mr. McCoy said. “We’re hoping to get a [legislative] sponsor in 2021 ... but it’s also been a really hard year to connect legislators with patients and doctors, and being able to hear their stories really does make a difference.”

In Nebraska, Marcus Snow, MD, a rheumatologist at Nebraska Medicine, in Omaha, said that the state’s new step therapy law will be a “great first step in helping to provide some guardrails” around the practice. He noted that turnaround requirements for insurer responses are “sorely needed.” However, he said that, because the bill doesn’t apply to all health plans, many Nebraskans still won’t benefit.

Dealing with step therapy is a daily “headache” for Dr. Snow, who says navigating the bureaucracy of prior authorization seems to be getting worse every year. Like his peers around the country, he spends an inordinate amount of time pushing appeals up the insurance company ranks to get access to treatments he believes will be most effective. But Snow says that, more than just being a mountain of tiresome red tape, these practices also intrude on the patient-provider relationship, casting an unsettling sense of uncertainty that the ultimate decision about the best course of action isn’t up to the doctor and patient at all.

“In the end, the insurance company is the judge and jury of my prescription,” Dr. Snow said. “They’d argue I can still prescribe it, but if it costs $70,000 a year – I don’t know who can afford that.”

Ms. Lynch, at the National Psoriasis Foundation, said their step therapy advocacy will continue to take a two-pronged approach. They will push for new and expanded protections at both state and federal levels. Protections are needed at both levels to make sure that all health plans regulated by all entities are covered. In the U.S. Senate and the House, step therapy bills were reintroduced this year. They would apply to health plans subject to the federal Employee Retirement Income Security Act, which governs employer-sponsored health coverage, and could close a big gap in existing protections. Oregon, New Jersey, and Arizona are at the top of the foundation’s advocacy list this year, according to Ms. Lynch.

“Folks are really starting to pay more attention to this issue,” she said. “And hearing those real-world stories and frustrations is definitely one of the most effective tools we have.”

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

Toxic metabolic encephalopathy (TME) is common and often lethal in hospitalized patients with COVID-19, new research shows. Results of a retrospective study show that of almost 4,500 patients with COVID-19, 12% were diagnosed with TME. Of these, 78% developed encephalopathy immediately prior to hospital admission. Septic encephalopathy, hypoxic-ischemic encephalopathy (HIE), and uremia were the most common causes, although multiple causes were present in close to 80% of patients. TME was also associated with a 24% higher risk of in-hospital death.

“We found that close to one in eight patients who were hospitalized with COVID-19 had TME that was not attributed to the effects of sedatives, and that this is incredibly common among these patients who are critically ill” said lead author Jennifer A. Frontera, MD, New York University.

“The general principle of our findings is to be more aggressive in TME; and from a neurologist perspective, the way to do this is to eliminate the effects of sedation, which is a confounder,” she said.

The study was published online March 16 in Neurocritical Care.
 

Drilling down

“Many neurological complications of COVID-19 are sequelae of severe illness or secondary effects of multisystem organ failure, but our previous work identified TME as the most common neurological complication,” Dr. Frontera said.

Previous research investigating encephalopathy among patients with COVID-19 included patients who may have been sedated or have had a positive Confusion Assessment Method (CAM) result.

“A lot of the delirium literature is effectively heterogeneous because there are a number of patients who are on sedative medication that, if you could turn it off, these patients would return to normal. Some may have underlying neurological issues that can be addressed, but you can›t get to the bottom of this unless you turn off the sedation,” Dr. Frontera noted.

“We wanted to be specific and try to drill down to see what the underlying cause of the encephalopathy was,” she said.

The researchers retrospectively analyzed data on 4,491 patients (≥ 18 years old) with COVID-19 who were admitted to four New York City hospitals between March 1, 2020, and May 20, 2020. Of these, 559 (12%) with TME were compared with 3,932 patients without TME.

The researchers looked at index admissions and included patients who had:

• New changes in mental status or significant worsening of mental status (in patients with baseline abnormal mental status).
• Hyperglycemia or  with transient focal neurologic deficits that resolved with glucose correction.
• An adequate washout of sedating medications (when relevant) prior to mental status assessment.

Potential etiologies included electrolyte abnormalities, organ failure, hypertensive encephalopathy, sepsis or active infection, fever, nutritional deficiency, and environmental injury.
 

Foreign environment

Most (78%) of the 559 patients diagnosed with TME had already developed encephalopathy immediately prior to hospital admission, the authors report. The most common etiologies of TME among hospitalized patients with COVID-19 are listed below.

Compared with patients without TME, those with TME – (all Ps < .001):

• Were older (76 vs. 62 years).
• Had higher rates of dementia (27% vs. 3%).
• Had higher rates of psychiatric history (20% vs. 10%).
• Were more often intubated (37% vs. 20%).
• Had a longer length of hospital stay (7.9 vs. 6.0 days).
• Were less often discharged home (25% vs. 66%).

“It’s no surprise that older patients and people with dementia or psychiatric illness are predisposed to becoming encephalopathic,” said Dr. Frontera. “Being in a foreign environment, such as a hospital, or being sleep-deprived in the ICU is likely to make them more confused during their hospital stay.”
 

Delirium as a symptom

In-hospital mortality or discharge to hospice was considerably higher in the TME versus non-TME patients (44% vs. 18%, respectively).

When the researchers adjusted for confounders (age, sex, race, worse Sequential Organ Failure Assessment score during hospitalization, ventilator status, study week, hospital location, and ICU care level) and excluded patients receiving only comfort care, they found that TME was associated with a 24% increased risk of in-hospital death (30% in patients with TME vs. 16% in those without TME).

The highest mortality risk was associated with hypoxemia, with 42% of patients with HIE dying during hospitalization, compared with 16% of patients without HIE (adjusted hazard ratio 1.56; 95% confidence interval, 1.21-2.00; P = .001).

“Not all patients who are intubated require sedation, but there’s generally a lot of hesitation in reducing or stopping sedation in some patients,” Dr. Frontera observed.

She acknowledged there are “many extremely sick patients whom you can’t ventilate without sedation.”

Nevertheless, “delirium in and of itself does not cause death. It’s a symptom, not a disease, and we have to figure out what causes it. Delirium might not need to be sedated, and it’s more important to see what the causal problem is.”
 

Independent predictor of death

Commenting on the study, Panayiotis N. Varelas, MD, PhD, vice president of the Neurocritical Care Society, said the study “approached the TME issue better than previously, namely allowing time for sedatives to wear off to have a better sample of patients with this syndrome.”

Dr. Varelas, who is chairman of the department of neurology and professor of neurology at Albany (N.Y.) Medical College, emphasized that TME “is not benign and, in patients with COVID-19, it is an independent predictor of in-hospital mortality.”

“One should take all possible measures … to avoid desaturation and hypotensive episodes and also aggressively treat SAE and uremic encephalopathy in hopes of improving the outcomes,” added Dr. Varelas, who was not involved with the study.

Also commenting on the study, Mitchell Elkind, MD, professor of neurology and epidemiology at Columbia University in New York, who was not associated with the research, said it “nicely distinguishes among the different causes of encephalopathy, including sepsis, hypoxia, and kidney failure … emphasizing just how sick these patients are.”

The study received no direct funding. Individual investigators were supported by grants from the National Institute on Aging and the National Institute of Neurological Disorders and Stroke. The investigators, Dr. Varelas, and Dr. Elkind have disclosed no relevant financial relationships.

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

Toxic metabolic encephalopathy (TME) is common and often lethal in hospitalized patients with COVID-19, new research shows. Results of a retrospective study show that of almost 4,500 patients with COVID-19, 12% were diagnosed with TME. Of these, 78% developed encephalopathy immediately prior to hospital admission. Septic encephalopathy, hypoxic-ischemic encephalopathy (HIE), and uremia were the most common causes, although multiple causes were present in close to 80% of patients. TME was also associated with a 24% higher risk of in-hospital death.

“We found that close to one in eight patients who were hospitalized with COVID-19 had TME that was not attributed to the effects of sedatives, and that this is incredibly common among these patients who are critically ill” said lead author Jennifer A. Frontera, MD, New York University.

“The general principle of our findings is to be more aggressive in TME; and from a neurologist perspective, the way to do this is to eliminate the effects of sedation, which is a confounder,” she said.

The study was published online March 16 in Neurocritical Care.
 

Drilling down

“Many neurological complications of COVID-19 are sequelae of severe illness or secondary effects of multisystem organ failure, but our previous work identified TME as the most common neurological complication,” Dr. Frontera said.

Previous research investigating encephalopathy among patients with COVID-19 included patients who may have been sedated or have had a positive Confusion Assessment Method (CAM) result.

“A lot of the delirium literature is effectively heterogeneous because there are a number of patients who are on sedative medication that, if you could turn it off, these patients would return to normal. Some may have underlying neurological issues that can be addressed, but you can›t get to the bottom of this unless you turn off the sedation,” Dr. Frontera noted.

“We wanted to be specific and try to drill down to see what the underlying cause of the encephalopathy was,” she said.

The researchers retrospectively analyzed data on 4,491 patients (≥ 18 years old) with COVID-19 who were admitted to four New York City hospitals between March 1, 2020, and May 20, 2020. Of these, 559 (12%) with TME were compared with 3,932 patients without TME.

The researchers looked at index admissions and included patients who had:

• New changes in mental status or significant worsening of mental status (in patients with baseline abnormal mental status).
• Hyperglycemia or  with transient focal neurologic deficits that resolved with glucose correction.
• An adequate washout of sedating medications (when relevant) prior to mental status assessment.

Potential etiologies included electrolyte abnormalities, organ failure, hypertensive encephalopathy, sepsis or active infection, fever, nutritional deficiency, and environmental injury.
 

Foreign environment

Most (78%) of the 559 patients diagnosed with TME had already developed encephalopathy immediately prior to hospital admission, the authors report. The most common etiologies of TME among hospitalized patients with COVID-19 are listed below.

Compared with patients without TME, those with TME – (all Ps < .001):

• Were older (76 vs. 62 years).
• Had higher rates of dementia (27% vs. 3%).
• Had higher rates of psychiatric history (20% vs. 10%).
• Were more often intubated (37% vs. 20%).
• Had a longer length of hospital stay (7.9 vs. 6.0 days).
• Were less often discharged home (25% vs. 66%).

“It’s no surprise that older patients and people with dementia or psychiatric illness are predisposed to becoming encephalopathic,” said Dr. Frontera. “Being in a foreign environment, such as a hospital, or being sleep-deprived in the ICU is likely to make them more confused during their hospital stay.”
 

Delirium as a symptom

In-hospital mortality or discharge to hospice was considerably higher in the TME versus non-TME patients (44% vs. 18%, respectively).

When the researchers adjusted for confounders (age, sex, race, worse Sequential Organ Failure Assessment score during hospitalization, ventilator status, study week, hospital location, and ICU care level) and excluded patients receiving only comfort care, they found that TME was associated with a 24% increased risk of in-hospital death (30% in patients with TME vs. 16% in those without TME).

The highest mortality risk was associated with hypoxemia, with 42% of patients with HIE dying during hospitalization, compared with 16% of patients without HIE (adjusted hazard ratio 1.56; 95% confidence interval, 1.21-2.00; P = .001).

“Not all patients who are intubated require sedation, but there’s generally a lot of hesitation in reducing or stopping sedation in some patients,” Dr. Frontera observed.

She acknowledged there are “many extremely sick patients whom you can’t ventilate without sedation.”

Nevertheless, “delirium in and of itself does not cause death. It’s a symptom, not a disease, and we have to figure out what causes it. Delirium might not need to be sedated, and it’s more important to see what the causal problem is.”
 

Independent predictor of death

Commenting on the study, Panayiotis N. Varelas, MD, PhD, vice president of the Neurocritical Care Society, said the study “approached the TME issue better than previously, namely allowing time for sedatives to wear off to have a better sample of patients with this syndrome.”

Dr. Varelas, who is chairman of the department of neurology and professor of neurology at Albany (N.Y.) Medical College, emphasized that TME “is not benign and, in patients with COVID-19, it is an independent predictor of in-hospital mortality.”

“One should take all possible measures … to avoid desaturation and hypotensive episodes and also aggressively treat SAE and uremic encephalopathy in hopes of improving the outcomes,” added Dr. Varelas, who was not involved with the study.

Also commenting on the study, Mitchell Elkind, MD, professor of neurology and epidemiology at Columbia University in New York, who was not associated with the research, said it “nicely distinguishes among the different causes of encephalopathy, including sepsis, hypoxia, and kidney failure … emphasizing just how sick these patients are.”

The study received no direct funding. Individual investigators were supported by grants from the National Institute on Aging and the National Institute of Neurological Disorders and Stroke. The investigators, Dr. Varelas, and Dr. Elkind have disclosed no relevant financial relationships.

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

Toxic metabolic encephalopathy (TME) is common and often lethal in hospitalized patients with COVID-19, new research shows. Results of a retrospective study show that of almost 4,500 patients with COVID-19, 12% were diagnosed with TME. Of these, 78% developed encephalopathy immediately prior to hospital admission. Septic encephalopathy, hypoxic-ischemic encephalopathy (HIE), and uremia were the most common causes, although multiple causes were present in close to 80% of patients. TME was also associated with a 24% higher risk of in-hospital death.

“We found that close to one in eight patients who were hospitalized with COVID-19 had TME that was not attributed to the effects of sedatives, and that this is incredibly common among these patients who are critically ill” said lead author Jennifer A. Frontera, MD, New York University.

“The general principle of our findings is to be more aggressive in TME; and from a neurologist perspective, the way to do this is to eliminate the effects of sedation, which is a confounder,” she said.

The study was published online March 16 in Neurocritical Care.
 

Drilling down

“Many neurological complications of COVID-19 are sequelae of severe illness or secondary effects of multisystem organ failure, but our previous work identified TME as the most common neurological complication,” Dr. Frontera said.

Previous research investigating encephalopathy among patients with COVID-19 included patients who may have been sedated or have had a positive Confusion Assessment Method (CAM) result.

“A lot of the delirium literature is effectively heterogeneous because there are a number of patients who are on sedative medication that, if you could turn it off, these patients would return to normal. Some may have underlying neurological issues that can be addressed, but you can›t get to the bottom of this unless you turn off the sedation,” Dr. Frontera noted.

“We wanted to be specific and try to drill down to see what the underlying cause of the encephalopathy was,” she said.

The researchers retrospectively analyzed data on 4,491 patients (≥ 18 years old) with COVID-19 who were admitted to four New York City hospitals between March 1, 2020, and May 20, 2020. Of these, 559 (12%) with TME were compared with 3,932 patients without TME.

The researchers looked at index admissions and included patients who had:

• New changes in mental status or significant worsening of mental status (in patients with baseline abnormal mental status).
• Hyperglycemia or  with transient focal neurologic deficits that resolved with glucose correction.
• An adequate washout of sedating medications (when relevant) prior to mental status assessment.

Potential etiologies included electrolyte abnormalities, organ failure, hypertensive encephalopathy, sepsis or active infection, fever, nutritional deficiency, and environmental injury.
 

Foreign environment

Most (78%) of the 559 patients diagnosed with TME had already developed encephalopathy immediately prior to hospital admission, the authors report. The most common etiologies of TME among hospitalized patients with COVID-19 are listed below.

Compared with patients without TME, those with TME – (all Ps < .001):

• Were older (76 vs. 62 years).
• Had higher rates of dementia (27% vs. 3%).
• Had higher rates of psychiatric history (20% vs. 10%).
• Were more often intubated (37% vs. 20%).
• Had a longer length of hospital stay (7.9 vs. 6.0 days).
• Were less often discharged home (25% vs. 66%).

“It’s no surprise that older patients and people with dementia or psychiatric illness are predisposed to becoming encephalopathic,” said Dr. Frontera. “Being in a foreign environment, such as a hospital, or being sleep-deprived in the ICU is likely to make them more confused during their hospital stay.”
 

Delirium as a symptom

In-hospital mortality or discharge to hospice was considerably higher in the TME versus non-TME patients (44% vs. 18%, respectively).

When the researchers adjusted for confounders (age, sex, race, worse Sequential Organ Failure Assessment score during hospitalization, ventilator status, study week, hospital location, and ICU care level) and excluded patients receiving only comfort care, they found that TME was associated with a 24% increased risk of in-hospital death (30% in patients with TME vs. 16% in those without TME).

The highest mortality risk was associated with hypoxemia, with 42% of patients with HIE dying during hospitalization, compared with 16% of patients without HIE (adjusted hazard ratio 1.56; 95% confidence interval, 1.21-2.00; P = .001).

“Not all patients who are intubated require sedation, but there’s generally a lot of hesitation in reducing or stopping sedation in some patients,” Dr. Frontera observed.

She acknowledged there are “many extremely sick patients whom you can’t ventilate without sedation.”

Nevertheless, “delirium in and of itself does not cause death. It’s a symptom, not a disease, and we have to figure out what causes it. Delirium might not need to be sedated, and it’s more important to see what the causal problem is.”
 

Independent predictor of death

Commenting on the study, Panayiotis N. Varelas, MD, PhD, vice president of the Neurocritical Care Society, said the study “approached the TME issue better than previously, namely allowing time for sedatives to wear off to have a better sample of patients with this syndrome.”

Dr. Varelas, who is chairman of the department of neurology and professor of neurology at Albany (N.Y.) Medical College, emphasized that TME “is not benign and, in patients with COVID-19, it is an independent predictor of in-hospital mortality.”

“One should take all possible measures … to avoid desaturation and hypotensive episodes and also aggressively treat SAE and uremic encephalopathy in hopes of improving the outcomes,” added Dr. Varelas, who was not involved with the study.

Also commenting on the study, Mitchell Elkind, MD, professor of neurology and epidemiology at Columbia University in New York, who was not associated with the research, said it “nicely distinguishes among the different causes of encephalopathy, including sepsis, hypoxia, and kidney failure … emphasizing just how sick these patients are.”

The study received no direct funding. Individual investigators were supported by grants from the National Institute on Aging and the National Institute of Neurological Disorders and Stroke. The investigators, Dr. Varelas, and Dr. Elkind have disclosed no relevant financial relationships.

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

Apremilast (Otezla) monotherapy may be an effective option in oligoarticular psoriatic arthritis, Alexis R. Ogdie, MD, reported at the 2021 Rheumatology Winter Clinical Symposium.

Her analysis of apremilast data from the CORRONA Registry was among several recent highlights in psoriatic arthritis (PsA) cited by speakers at the meeting. Other significant developments included a large pan-Scandinavian study that reassuringly found no increased risk of solid cancers in tumor necrosis factor (TNF) inhibitor–treated patients with PsA, and evidence to suggest a sex difference in the efficacy of both secukinumab (Cosentyx) and adalimumab (Humira), with men responding better than women to two biologics with differing mechanisms of action.
 

A role for apremilast in oligoarticular disease?

Dr. Ogdie presented an analysis of 150 patients in the U.S. observational CORRONA Registry who initiated monotherapy for oligoarticular PsA and were followed for 6 months. Thirty-four started on apremilast, 15 on methotrexate, and 101 on a biologic. Even though the apremilast group had higher baseline disease activity than did those who started on methotrexate, at 6 months a swollen joint count of 1 or 0 was present in 41% of the apremilast-treated patients, compared with none on methotrexate and 15% on a biologic agent.

A tender joint count of 0-1 was documented at 6 months in 24% of patients on apremilast, 13% with methotrexate, and 21% on a biologic agent. Apremilast’s numeric superiority in outcomes compared to methotrexate in this exploratory study wasn’t subjected to statistical analysis because of the small sample size. However, the ongoing phase 4, double-blind, placebo-controlled, multicenter FOREMOST trial in 330 patients with early oligoarticular PsA should provide more definitive efficacy data, noted Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia.

RWCS program director Arthur Kavanaugh, MD, said, “The most recent EULAR [European Alliance of Associations for Rheumatology] PsA guidelines totally discount apremilast, and I think mostly on the basis of cost, but then they also say that in groups of people it’s not as effective as methotrexate.”

“This study shows to me that, even though it’s a registry, with all the caveats about getting data from registries, apremilast certainly can be an effective drug,” said Dr. Kavanaugh, a rheumatologist and professor of medicine at the University of California, San Diego.

Another valuable piece of information from the CORRONA analysis is that it zeros in on patients with oligoarticular PsA.

“Almost all of our PsA studies are focused on people with polyarticular disease. What about those who have lesser involvement? That, of course, is important in the clinic,” he noted.

Dr. Ogdie concurred.

“If we study only polyarticular disease and we make all of our assumptions based on polyarticular disease, we might be leaving out at least half of the patients with PsA. And those patients may not need a bigger gun. Apremilast and methotrexate are kind of in the same group for that mild oligoarticular disease, and they probably work just fine,” she said.

A final point: “We really don’t have good outcome measures to study oligoarticular disease well. The ACR20 is not good because a 20% improvement in three joints is not readily measurable. That’s why trialists enroll patients with high joint count numbers,” according to the rheumatologist.

No increased risk of solid cancers in PsA patients treated with TNF inhibitors

A new analysis of clinical rheumatology registries in five Nordic countries finally puts to rest any concerns that treatment of PsA with TNF inhibitors is associated with increased risk of solid cancers. The same group previously reported no link between TNF inhibitors and lymphoma in PsA.

The solid cancers study included 9,655 PsA patients who started a first TNF inhibitor during 2001-2017, 14,809 others not treated with biologics, and 31,350 matched general population controls. Linkage to Swedish, Norwegian, Danish, Icelandic, and Finnish national cancer registries showed that the adjusted risk for solid cancer in TNF inhibitor–treated, compared with biologic-naive PsA patients, was 1.0. Similarly, the pooled standardized incidence ratio of solid cancer in TNF inhibitor–treated PsA patients compared to the general population was 1.0. There was no signal of a differential risk for incident cancer for any of the eight malignancies studied: lung, colorectal, breast, prostate, uterine, brain, liver, and pancreatic cancer.

“I like this study a lot because it’s specific to PsA rather than extrapolating from rheumatoid arthritis data, where we have a bunch more information for a much longer period of time, but it’s a different population,” Dr. Kavanaugh said.

Dr. Ogdie said, “I talk to my patients about this particular study or the same group’s earlier lymphoma study all the time.”

“I have to say, these are important data for the dermatology world because there are dermatologists who are still not convinced that TNF inhibitors don’t have an increased risk of malignancy. This kind of information is going to be helpful,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.
 

Greater efficacy for biologics in males than females with PsA?

A secondary analysis of the phase 3b EXCEED trial raised the intriguing possibility that both secukinumab, an interleukin-17A inhibitor, and adalimumab, a TNF inhibitor, have greater efficacy in men than in women with PsA. In this randomized trial of 853 biologic-naive patients with PsA, the ACR20 response rate to secukinumab at week 52 was 61% in females versus 74% in males, with ACR50 rates of 43% in females and 55.3% in males. The ACR20 rate with adalimumab was 51.5% in females and 70.2% in males. Similarly, the corresponding ACR50s were 32.6% and 55.3%, respectively. Minimal disease activity was achieved in 36.2% of women and 51% of men on secukinumab, and in 24.2% of women and 49.8% of men on adalimumab.

“These are randomized patients, so you really shouldn’t see these big differences in minimal disease activity,” Dr. Ogdie noted. “The question is why do men seem to respond better to therapy than women? I don’t think it’s the fibromyalgia-ness. There’s probably some biologic rationale for this that we just don’t understand yet. Maybe hormonal interactions.”

This gender difference in response is an important issue because it can potentially distort outcomes in head-to-head drug trials, Dr. Ruderman added.

“That gender difference is not likely to be huge if you’re looking at a placebo-controlled trial because the difference between the active drug and placebo is going to outweigh it. But when you have two active drugs, if there’s an imbalance in terms of how many men or women there are on each of the two drugs, you may end up with an efficacy difference that’s not real but is based on gender and not response to the drug,” he explained.

Roy M. Fleischmann, MD, a rheumatologist and clinical trialist at the University of Texas, Dallas, rose from the audience to pronounce the EXCEED male-versus-female analysis “very interesting.”

“We should go back and look at other trials and see if that occurred, and if it did, then we have to think about that going forward,” he proposed.

Dr. Ogdie, Dr. Kavanaugh, and Dr. Ruderman reported having financial relationships with numerous pharmaceutical companies.

[email protected]

Apremilast (Otezla) monotherapy may be an effective option in oligoarticular psoriatic arthritis, Alexis R. Ogdie, MD, reported at the 2021 Rheumatology Winter Clinical Symposium.

Her analysis of apremilast data from the CORRONA Registry was among several recent highlights in psoriatic arthritis (PsA) cited by speakers at the meeting. Other significant developments included a large pan-Scandinavian study that reassuringly found no increased risk of solid cancers in tumor necrosis factor (TNF) inhibitor–treated patients with PsA, and evidence to suggest a sex difference in the efficacy of both secukinumab (Cosentyx) and adalimumab (Humira), with men responding better than women to two biologics with differing mechanisms of action.
 

A role for apremilast in oligoarticular disease?

Dr. Ogdie presented an analysis of 150 patients in the U.S. observational CORRONA Registry who initiated monotherapy for oligoarticular PsA and were followed for 6 months. Thirty-four started on apremilast, 15 on methotrexate, and 101 on a biologic. Even though the apremilast group had higher baseline disease activity than did those who started on methotrexate, at 6 months a swollen joint count of 1 or 0 was present in 41% of the apremilast-treated patients, compared with none on methotrexate and 15% on a biologic agent.

A tender joint count of 0-1 was documented at 6 months in 24% of patients on apremilast, 13% with methotrexate, and 21% on a biologic agent. Apremilast’s numeric superiority in outcomes compared to methotrexate in this exploratory study wasn’t subjected to statistical analysis because of the small sample size. However, the ongoing phase 4, double-blind, placebo-controlled, multicenter FOREMOST trial in 330 patients with early oligoarticular PsA should provide more definitive efficacy data, noted Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia.

RWCS program director Arthur Kavanaugh, MD, said, “The most recent EULAR [European Alliance of Associations for Rheumatology] PsA guidelines totally discount apremilast, and I think mostly on the basis of cost, but then they also say that in groups of people it’s not as effective as methotrexate.”

“This study shows to me that, even though it’s a registry, with all the caveats about getting data from registries, apremilast certainly can be an effective drug,” said Dr. Kavanaugh, a rheumatologist and professor of medicine at the University of California, San Diego.

Another valuable piece of information from the CORRONA analysis is that it zeros in on patients with oligoarticular PsA.

“Almost all of our PsA studies are focused on people with polyarticular disease. What about those who have lesser involvement? That, of course, is important in the clinic,” he noted.

Dr. Ogdie concurred.

“If we study only polyarticular disease and we make all of our assumptions based on polyarticular disease, we might be leaving out at least half of the patients with PsA. And those patients may not need a bigger gun. Apremilast and methotrexate are kind of in the same group for that mild oligoarticular disease, and they probably work just fine,” she said.

A final point: “We really don’t have good outcome measures to study oligoarticular disease well. The ACR20 is not good because a 20% improvement in three joints is not readily measurable. That’s why trialists enroll patients with high joint count numbers,” according to the rheumatologist.

No increased risk of solid cancers in PsA patients treated with TNF inhibitors

A new analysis of clinical rheumatology registries in five Nordic countries finally puts to rest any concerns that treatment of PsA with TNF inhibitors is associated with increased risk of solid cancers. The same group previously reported no link between TNF inhibitors and lymphoma in PsA.

The solid cancers study included 9,655 PsA patients who started a first TNF inhibitor during 2001-2017, 14,809 others not treated with biologics, and 31,350 matched general population controls. Linkage to Swedish, Norwegian, Danish, Icelandic, and Finnish national cancer registries showed that the adjusted risk for solid cancer in TNF inhibitor–treated, compared with biologic-naive PsA patients, was 1.0. Similarly, the pooled standardized incidence ratio of solid cancer in TNF inhibitor–treated PsA patients compared to the general population was 1.0. There was no signal of a differential risk for incident cancer for any of the eight malignancies studied: lung, colorectal, breast, prostate, uterine, brain, liver, and pancreatic cancer.

“I like this study a lot because it’s specific to PsA rather than extrapolating from rheumatoid arthritis data, where we have a bunch more information for a much longer period of time, but it’s a different population,” Dr. Kavanaugh said.

Dr. Ogdie said, “I talk to my patients about this particular study or the same group’s earlier lymphoma study all the time.”

“I have to say, these are important data for the dermatology world because there are dermatologists who are still not convinced that TNF inhibitors don’t have an increased risk of malignancy. This kind of information is going to be helpful,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.
 

Greater efficacy for biologics in males than females with PsA?

A secondary analysis of the phase 3b EXCEED trial raised the intriguing possibility that both secukinumab, an interleukin-17A inhibitor, and adalimumab, a TNF inhibitor, have greater efficacy in men than in women with PsA. In this randomized trial of 853 biologic-naive patients with PsA, the ACR20 response rate to secukinumab at week 52 was 61% in females versus 74% in males, with ACR50 rates of 43% in females and 55.3% in males. The ACR20 rate with adalimumab was 51.5% in females and 70.2% in males. Similarly, the corresponding ACR50s were 32.6% and 55.3%, respectively. Minimal disease activity was achieved in 36.2% of women and 51% of men on secukinumab, and in 24.2% of women and 49.8% of men on adalimumab.

“These are randomized patients, so you really shouldn’t see these big differences in minimal disease activity,” Dr. Ogdie noted. “The question is why do men seem to respond better to therapy than women? I don’t think it’s the fibromyalgia-ness. There’s probably some biologic rationale for this that we just don’t understand yet. Maybe hormonal interactions.”

This gender difference in response is an important issue because it can potentially distort outcomes in head-to-head drug trials, Dr. Ruderman added.

“That gender difference is not likely to be huge if you’re looking at a placebo-controlled trial because the difference between the active drug and placebo is going to outweigh it. But when you have two active drugs, if there’s an imbalance in terms of how many men or women there are on each of the two drugs, you may end up with an efficacy difference that’s not real but is based on gender and not response to the drug,” he explained.

Roy M. Fleischmann, MD, a rheumatologist and clinical trialist at the University of Texas, Dallas, rose from the audience to pronounce the EXCEED male-versus-female analysis “very interesting.”

“We should go back and look at other trials and see if that occurred, and if it did, then we have to think about that going forward,” he proposed.

Dr. Ogdie, Dr. Kavanaugh, and Dr. Ruderman reported having financial relationships with numerous pharmaceutical companies.

[email protected]

Apremilast (Otezla) monotherapy may be an effective option in oligoarticular psoriatic arthritis, Alexis R. Ogdie, MD, reported at the 2021 Rheumatology Winter Clinical Symposium.

Her analysis of apremilast data from the CORRONA Registry was among several recent highlights in psoriatic arthritis (PsA) cited by speakers at the meeting. Other significant developments included a large pan-Scandinavian study that reassuringly found no increased risk of solid cancers in tumor necrosis factor (TNF) inhibitor–treated patients with PsA, and evidence to suggest a sex difference in the efficacy of both secukinumab (Cosentyx) and adalimumab (Humira), with men responding better than women to two biologics with differing mechanisms of action.
 

A role for apremilast in oligoarticular disease?

Dr. Ogdie presented an analysis of 150 patients in the U.S. observational CORRONA Registry who initiated monotherapy for oligoarticular PsA and were followed for 6 months. Thirty-four started on apremilast, 15 on methotrexate, and 101 on a biologic. Even though the apremilast group had higher baseline disease activity than did those who started on methotrexate, at 6 months a swollen joint count of 1 or 0 was present in 41% of the apremilast-treated patients, compared with none on methotrexate and 15% on a biologic agent.

A tender joint count of 0-1 was documented at 6 months in 24% of patients on apremilast, 13% with methotrexate, and 21% on a biologic agent. Apremilast’s numeric superiority in outcomes compared to methotrexate in this exploratory study wasn’t subjected to statistical analysis because of the small sample size. However, the ongoing phase 4, double-blind, placebo-controlled, multicenter FOREMOST trial in 330 patients with early oligoarticular PsA should provide more definitive efficacy data, noted Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia.

RWCS program director Arthur Kavanaugh, MD, said, “The most recent EULAR [European Alliance of Associations for Rheumatology] PsA guidelines totally discount apremilast, and I think mostly on the basis of cost, but then they also say that in groups of people it’s not as effective as methotrexate.”

“This study shows to me that, even though it’s a registry, with all the caveats about getting data from registries, apremilast certainly can be an effective drug,” said Dr. Kavanaugh, a rheumatologist and professor of medicine at the University of California, San Diego.

Another valuable piece of information from the CORRONA analysis is that it zeros in on patients with oligoarticular PsA.

“Almost all of our PsA studies are focused on people with polyarticular disease. What about those who have lesser involvement? That, of course, is important in the clinic,” he noted.

Dr. Ogdie concurred.

“If we study only polyarticular disease and we make all of our assumptions based on polyarticular disease, we might be leaving out at least half of the patients with PsA. And those patients may not need a bigger gun. Apremilast and methotrexate are kind of in the same group for that mild oligoarticular disease, and they probably work just fine,” she said.

A final point: “We really don’t have good outcome measures to study oligoarticular disease well. The ACR20 is not good because a 20% improvement in three joints is not readily measurable. That’s why trialists enroll patients with high joint count numbers,” according to the rheumatologist.

No increased risk of solid cancers in PsA patients treated with TNF inhibitors

A new analysis of clinical rheumatology registries in five Nordic countries finally puts to rest any concerns that treatment of PsA with TNF inhibitors is associated with increased risk of solid cancers. The same group previously reported no link between TNF inhibitors and lymphoma in PsA.

The solid cancers study included 9,655 PsA patients who started a first TNF inhibitor during 2001-2017, 14,809 others not treated with biologics, and 31,350 matched general population controls. Linkage to Swedish, Norwegian, Danish, Icelandic, and Finnish national cancer registries showed that the adjusted risk for solid cancer in TNF inhibitor–treated, compared with biologic-naive PsA patients, was 1.0. Similarly, the pooled standardized incidence ratio of solid cancer in TNF inhibitor–treated PsA patients compared to the general population was 1.0. There was no signal of a differential risk for incident cancer for any of the eight malignancies studied: lung, colorectal, breast, prostate, uterine, brain, liver, and pancreatic cancer.

“I like this study a lot because it’s specific to PsA rather than extrapolating from rheumatoid arthritis data, where we have a bunch more information for a much longer period of time, but it’s a different population,” Dr. Kavanaugh said.

Dr. Ogdie said, “I talk to my patients about this particular study or the same group’s earlier lymphoma study all the time.”

“I have to say, these are important data for the dermatology world because there are dermatologists who are still not convinced that TNF inhibitors don’t have an increased risk of malignancy. This kind of information is going to be helpful,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.
 

Greater efficacy for biologics in males than females with PsA?

A secondary analysis of the phase 3b EXCEED trial raised the intriguing possibility that both secukinumab, an interleukin-17A inhibitor, and adalimumab, a TNF inhibitor, have greater efficacy in men than in women with PsA. In this randomized trial of 853 biologic-naive patients with PsA, the ACR20 response rate to secukinumab at week 52 was 61% in females versus 74% in males, with ACR50 rates of 43% in females and 55.3% in males. The ACR20 rate with adalimumab was 51.5% in females and 70.2% in males. Similarly, the corresponding ACR50s were 32.6% and 55.3%, respectively. Minimal disease activity was achieved in 36.2% of women and 51% of men on secukinumab, and in 24.2% of women and 49.8% of men on adalimumab.

“These are randomized patients, so you really shouldn’t see these big differences in minimal disease activity,” Dr. Ogdie noted. “The question is why do men seem to respond better to therapy than women? I don’t think it’s the fibromyalgia-ness. There’s probably some biologic rationale for this that we just don’t understand yet. Maybe hormonal interactions.”

This gender difference in response is an important issue because it can potentially distort outcomes in head-to-head drug trials, Dr. Ruderman added.

“That gender difference is not likely to be huge if you’re looking at a placebo-controlled trial because the difference between the active drug and placebo is going to outweigh it. But when you have two active drugs, if there’s an imbalance in terms of how many men or women there are on each of the two drugs, you may end up with an efficacy difference that’s not real but is based on gender and not response to the drug,” he explained.

Roy M. Fleischmann, MD, a rheumatologist and clinical trialist at the University of Texas, Dallas, rose from the audience to pronounce the EXCEED male-versus-female analysis “very interesting.”

“We should go back and look at other trials and see if that occurred, and if it did, then we have to think about that going forward,” he proposed.

Dr. Ogdie, Dr. Kavanaugh, and Dr. Ruderman reported having financial relationships with numerous pharmaceutical companies.

[email protected]

Two reports support the safety and immunogenicity of SARS-CoV-2 mRNA vaccines in patients with rheumatic and musculoskeletal diseases (RMDs) and represent the first available data on such patients.

peterschreiber_media/iStock/Getty Images

In an observational cohort study published in Annals of the Rheumatic Diseases, Caoilfhionn M. Connolly, MD, of Johns Hopkins University, Baltimore, and colleagues reviewed data from 325 adults with RMDs who received the first dose of SARS-CoV-2 mRNA vaccine during the period of Dec. 17, 2020, to Feb. 11, 2021. Of these, 51% received the Pfizer/BioNTech vaccine and 49% received the Moderna vaccine.

The patients, who were invited to participate on social media, were aged 34-54 years, 96% were women, and 89% were White. Inflammatory arthritis was the most common RMD condition (38%), followed by systemic lupus erythematosus (28%) and overlap connective tissue disease (19%). The patients were using a range of immunomodulatory treatment regimens, including nonbiologic disease modifying antirheumatic drugs (DMARDs) in 44%, biologics in 19%, and combination therapy in 37%.

Overall, 89% of patients reported localized symptoms of pain, swelling, and erythema, and 69% reported systemic symptoms. Fatigue was the most common systemic symptom, and 7.4% reported severe fatigue.

None of the patients experienced allergic reactions requiring epinephrine, and 3% reported new infections that required treatment.

“These early, reassuring results may ameliorate concern among patients and provide guidance for rheumatology providers in critical discussions regarding vaccine hesitancy or refusal,” they concluded.

Antibody responses

In another study published in Annals of the Rheumatic Diseases by the same group of researchers, antibody responses against the receptor binding domain of the SARS-CoV-2 spike protein were seen in 74% of 123 adults with an RMD at 18-26 days after receiving a first dose of SARS-CoV-2 mRNA vaccine (52% Pfizer vaccine and 48% Moderna) between Jan. 8, 2021, and Feb. 12, 2021.

The most common diagnoses in these patients were inflammatory arthritis (28%), systemic lupus erythematosus (20%), and Sjögren’s syndrome (13%). A total of 28% of participants reported taking no immunomodulatory agents, 19% reported nonbiologic DMARDs, 14% reported biologic DMARDs, and 19% reported combination therapy.

Although no differences appeared based on disease groups or overall categories of immunomodulatory therapies, patients whose treatment included mycophenolate or rituximab were significantly less likely to develop antibody responses than were patients not taking these medications (P = .001 and P = .04, respectively). Although rituximab and methotrexate have been associated with reduced responses to vaccines such as the flu vaccine, methotrexate was not associated with reduced vaccine response in this study. A total of 94% of patients taking a tumor necrosis factor inhibitor had detectable antibodies.

The studies’ findings were limited by several factors including a lack of longer-term safety data; the small, nonrandomized sample of mainly white women; limited information on immunomodulatory drug dosage and timing; lack of serial antibody measurements; use of an enzyme immunoassay designed to detect antibody response after natural infection; and the inclusion of data only on the first dose of a two-dose vaccine series, the researchers noted. However, the data should provide additional reassurance to RMD patients and their health care teams about vaccination against COVID-19, they said.

Both studies were supported by the Ben-Dov family. In addition, the studies were supported by grants to various study authors from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Transplantation and Immunology Research Network of the American Society of Transplantation. One author disclosed financial relationships with Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. The other researchers had no financial conflicts to disclose.

Two reports support the safety and immunogenicity of SARS-CoV-2 mRNA vaccines in patients with rheumatic and musculoskeletal diseases (RMDs) and represent the first available data on such patients.

peterschreiber_media/iStock/Getty Images

In an observational cohort study published in Annals of the Rheumatic Diseases, Caoilfhionn M. Connolly, MD, of Johns Hopkins University, Baltimore, and colleagues reviewed data from 325 adults with RMDs who received the first dose of SARS-CoV-2 mRNA vaccine during the period of Dec. 17, 2020, to Feb. 11, 2021. Of these, 51% received the Pfizer/BioNTech vaccine and 49% received the Moderna vaccine.

The patients, who were invited to participate on social media, were aged 34-54 years, 96% were women, and 89% were White. Inflammatory arthritis was the most common RMD condition (38%), followed by systemic lupus erythematosus (28%) and overlap connective tissue disease (19%). The patients were using a range of immunomodulatory treatment regimens, including nonbiologic disease modifying antirheumatic drugs (DMARDs) in 44%, biologics in 19%, and combination therapy in 37%.

Overall, 89% of patients reported localized symptoms of pain, swelling, and erythema, and 69% reported systemic symptoms. Fatigue was the most common systemic symptom, and 7.4% reported severe fatigue.

None of the patients experienced allergic reactions requiring epinephrine, and 3% reported new infections that required treatment.

“These early, reassuring results may ameliorate concern among patients and provide guidance for rheumatology providers in critical discussions regarding vaccine hesitancy or refusal,” they concluded.

Antibody responses

In another study published in Annals of the Rheumatic Diseases by the same group of researchers, antibody responses against the receptor binding domain of the SARS-CoV-2 spike protein were seen in 74% of 123 adults with an RMD at 18-26 days after receiving a first dose of SARS-CoV-2 mRNA vaccine (52% Pfizer vaccine and 48% Moderna) between Jan. 8, 2021, and Feb. 12, 2021.

The most common diagnoses in these patients were inflammatory arthritis (28%), systemic lupus erythematosus (20%), and Sjögren’s syndrome (13%). A total of 28% of participants reported taking no immunomodulatory agents, 19% reported nonbiologic DMARDs, 14% reported biologic DMARDs, and 19% reported combination therapy.

Although no differences appeared based on disease groups or overall categories of immunomodulatory therapies, patients whose treatment included mycophenolate or rituximab were significantly less likely to develop antibody responses than were patients not taking these medications (P = .001 and P = .04, respectively). Although rituximab and methotrexate have been associated with reduced responses to vaccines such as the flu vaccine, methotrexate was not associated with reduced vaccine response in this study. A total of 94% of patients taking a tumor necrosis factor inhibitor had detectable antibodies.

The studies’ findings were limited by several factors including a lack of longer-term safety data; the small, nonrandomized sample of mainly white women; limited information on immunomodulatory drug dosage and timing; lack of serial antibody measurements; use of an enzyme immunoassay designed to detect antibody response after natural infection; and the inclusion of data only on the first dose of a two-dose vaccine series, the researchers noted. However, the data should provide additional reassurance to RMD patients and their health care teams about vaccination against COVID-19, they said.

Both studies were supported by the Ben-Dov family. In addition, the studies were supported by grants to various study authors from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Transplantation and Immunology Research Network of the American Society of Transplantation. One author disclosed financial relationships with Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. The other researchers had no financial conflicts to disclose.

Two reports support the safety and immunogenicity of SARS-CoV-2 mRNA vaccines in patients with rheumatic and musculoskeletal diseases (RMDs) and represent the first available data on such patients.

peterschreiber_media/iStock/Getty Images

In an observational cohort study published in Annals of the Rheumatic Diseases, Caoilfhionn M. Connolly, MD, of Johns Hopkins University, Baltimore, and colleagues reviewed data from 325 adults with RMDs who received the first dose of SARS-CoV-2 mRNA vaccine during the period of Dec. 17, 2020, to Feb. 11, 2021. Of these, 51% received the Pfizer/BioNTech vaccine and 49% received the Moderna vaccine.

The patients, who were invited to participate on social media, were aged 34-54 years, 96% were women, and 89% were White. Inflammatory arthritis was the most common RMD condition (38%), followed by systemic lupus erythematosus (28%) and overlap connective tissue disease (19%). The patients were using a range of immunomodulatory treatment regimens, including nonbiologic disease modifying antirheumatic drugs (DMARDs) in 44%, biologics in 19%, and combination therapy in 37%.

Overall, 89% of patients reported localized symptoms of pain, swelling, and erythema, and 69% reported systemic symptoms. Fatigue was the most common systemic symptom, and 7.4% reported severe fatigue.

None of the patients experienced allergic reactions requiring epinephrine, and 3% reported new infections that required treatment.

“These early, reassuring results may ameliorate concern among patients and provide guidance for rheumatology providers in critical discussions regarding vaccine hesitancy or refusal,” they concluded.

Antibody responses

In another study published in Annals of the Rheumatic Diseases by the same group of researchers, antibody responses against the receptor binding domain of the SARS-CoV-2 spike protein were seen in 74% of 123 adults with an RMD at 18-26 days after receiving a first dose of SARS-CoV-2 mRNA vaccine (52% Pfizer vaccine and 48% Moderna) between Jan. 8, 2021, and Feb. 12, 2021.

The most common diagnoses in these patients were inflammatory arthritis (28%), systemic lupus erythematosus (20%), and Sjögren’s syndrome (13%). A total of 28% of participants reported taking no immunomodulatory agents, 19% reported nonbiologic DMARDs, 14% reported biologic DMARDs, and 19% reported combination therapy.

Although no differences appeared based on disease groups or overall categories of immunomodulatory therapies, patients whose treatment included mycophenolate or rituximab were significantly less likely to develop antibody responses than were patients not taking these medications (P = .001 and P = .04, respectively). Although rituximab and methotrexate have been associated with reduced responses to vaccines such as the flu vaccine, methotrexate was not associated with reduced vaccine response in this study. A total of 94% of patients taking a tumor necrosis factor inhibitor had detectable antibodies.

The studies’ findings were limited by several factors including a lack of longer-term safety data; the small, nonrandomized sample of mainly white women; limited information on immunomodulatory drug dosage and timing; lack of serial antibody measurements; use of an enzyme immunoassay designed to detect antibody response after natural infection; and the inclusion of data only on the first dose of a two-dose vaccine series, the researchers noted. However, the data should provide additional reassurance to RMD patients and their health care teams about vaccination against COVID-19, they said.

Both studies were supported by the Ben-Dov family. In addition, the studies were supported by grants to various study authors from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Transplantation and Immunology Research Network of the American Society of Transplantation. One author disclosed financial relationships with Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. The other researchers had no financial conflicts to disclose.

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

The Food and Drug Administration has approved rilonacept (Arcalyst) to treat recurrent pericarditis and reduce the risk for recurrence in adults and children 12 years and older.

Approval of the weekly subcutaneous injection offers patients the first and only FDA-approved therapy for recurrent pericarditis, the agency said in a release.

Recurrent pericarditis is characterized by a remitting relapsing inflammation of the pericardium, and therapeutic options have been limited to NSAIDs, colchicine, and corticosteroids.

Rilonacept is a recombinant fusion protein that blocks interleukin-1 alpha and interleukin-1 beta signaling. It is already approved by the FDA to treat a group of rare inherited inflammatory diseases called cryopyrin-associated periodic syndromes.

The new indication is based on the pivotal phase 3 RHAPSODY trial in 86 patients with acute symptoms of recurrent pericarditis and systemic inflammation. After randomization, pericarditis recurred in 2 of 30 patients (7%) treated with rilonacept and in 23 of 31 patients (74%) treated with placebo, representing a 96% reduction in the relative risk for recurrence with rilonacept.

Patients who received rilonacept were also pain free or had minimal pain on 98% of trial days, whereas those who received placebo had minimal or no pain on 46% of trial days.

The most common adverse effects of rilonacept are injection-site reactions and upper-respiratory tract infections.

Serious, life-threatening infections have been reported in patients taking rilonacept, according to the FDA. Patients with active or chronic infections should not take the drug.

The FDA label also advises that patients should avoid live vaccines while taking rilonacept and that it should be discontinued if a hypersensitivity reaction occurs.

The commercial launch is expected in April, according to the company.

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

The Food and Drug Administration has approved rilonacept (Arcalyst) to treat recurrent pericarditis and reduce the risk for recurrence in adults and children 12 years and older.

Approval of the weekly subcutaneous injection offers patients the first and only FDA-approved therapy for recurrent pericarditis, the agency said in a release.

Recurrent pericarditis is characterized by a remitting relapsing inflammation of the pericardium, and therapeutic options have been limited to NSAIDs, colchicine, and corticosteroids.

Rilonacept is a recombinant fusion protein that blocks interleukin-1 alpha and interleukin-1 beta signaling. It is already approved by the FDA to treat a group of rare inherited inflammatory diseases called cryopyrin-associated periodic syndromes.

The new indication is based on the pivotal phase 3 RHAPSODY trial in 86 patients with acute symptoms of recurrent pericarditis and systemic inflammation. After randomization, pericarditis recurred in 2 of 30 patients (7%) treated with rilonacept and in 23 of 31 patients (74%) treated with placebo, representing a 96% reduction in the relative risk for recurrence with rilonacept.

Patients who received rilonacept were also pain free or had minimal pain on 98% of trial days, whereas those who received placebo had minimal or no pain on 46% of trial days.

The most common adverse effects of rilonacept are injection-site reactions and upper-respiratory tract infections.

Serious, life-threatening infections have been reported in patients taking rilonacept, according to the FDA. Patients with active or chronic infections should not take the drug.

The FDA label also advises that patients should avoid live vaccines while taking rilonacept and that it should be discontinued if a hypersensitivity reaction occurs.

The commercial launch is expected in April, according to the company.

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

The Food and Drug Administration has approved rilonacept (Arcalyst) to treat recurrent pericarditis and reduce the risk for recurrence in adults and children 12 years and older.

Approval of the weekly subcutaneous injection offers patients the first and only FDA-approved therapy for recurrent pericarditis, the agency said in a release.

Recurrent pericarditis is characterized by a remitting relapsing inflammation of the pericardium, and therapeutic options have been limited to NSAIDs, colchicine, and corticosteroids.

Rilonacept is a recombinant fusion protein that blocks interleukin-1 alpha and interleukin-1 beta signaling. It is already approved by the FDA to treat a group of rare inherited inflammatory diseases called cryopyrin-associated periodic syndromes.

The new indication is based on the pivotal phase 3 RHAPSODY trial in 86 patients with acute symptoms of recurrent pericarditis and systemic inflammation. After randomization, pericarditis recurred in 2 of 30 patients (7%) treated with rilonacept and in 23 of 31 patients (74%) treated with placebo, representing a 96% reduction in the relative risk for recurrence with rilonacept.

Patients who received rilonacept were also pain free or had minimal pain on 98% of trial days, whereas those who received placebo had minimal or no pain on 46% of trial days.

The most common adverse effects of rilonacept are injection-site reactions and upper-respiratory tract infections.

Serious, life-threatening infections have been reported in patients taking rilonacept, according to the FDA. Patients with active or chronic infections should not take the drug.

The FDA label also advises that patients should avoid live vaccines while taking rilonacept and that it should be discontinued if a hypersensitivity reaction occurs.

The commercial launch is expected in April, according to the company.

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