Lupus & Connective Tissue Diseases

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

Lupus nephritis (LN) affects approximately 25%-60% of patients with systemic lupus erythematosus. Currently, guideline-directed therapy recommends a combination of steroids plus either mycophenolate mofetil or cyclophosphamide. Despite treatment, about 10%-30% of LN patients will progress to end-stage kidney disease. 

Fortunately, over the past 2 years, the FDA approved two novel agents that expand treatment options for patients with active disease who have received standard-of-care therapy.  

In this ReCAP, Dr Joan Merrill, of the University of Oklahoma Health Sciences Center, reports on the B-lymphocyte stimulator–specific inhibitor belimumab, which was evaluated in the BLISS-LN trial, and the oral calcineurin inhibitor voclosporin, which was assessed in the AURORA trials.  

Dr Merrill discusses how these recently approved medications fit into the standard of care for LN patients. 

--

Joan Merrill, MD, Professor, Department of Medicine, Division of Rheumatology, University of Oklahoma Health Sciences Center; Director of Clinical Projects, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 

Joan Merrill, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a speaker or a member of a speakers bureau for: Biogen 

Received research grant from: Bristol-Myers Squibb; GlaxoSmithKline 

Received income in an amount equal to or greater than $250 from: AbbVie; Alexion; Amgen; AstraZeneca; Aurinia; Bristol-Myers Squibb; EMD Serono; Genentech; Gilead; GlaxoSmithKline; Lilly; Merck; Provention; RemeGen; Sanofi; UCB; Zenas 

Received research grant from: AbbVie; AstraZeneca; BeiGene; Pharmacyclics; TG Therapeutics 

Lupus nephritis (LN) affects approximately 25%-60% of patients with systemic lupus erythematosus. Currently, guideline-directed therapy recommends a combination of steroids plus either mycophenolate mofetil or cyclophosphamide. Despite treatment, about 10%-30% of LN patients will progress to end-stage kidney disease. 

Fortunately, over the past 2 years, the FDA approved two novel agents that expand treatment options for patients with active disease who have received standard-of-care therapy.  

In this ReCAP, Dr Joan Merrill, of the University of Oklahoma Health Sciences Center, reports on the B-lymphocyte stimulator–specific inhibitor belimumab, which was evaluated in the BLISS-LN trial, and the oral calcineurin inhibitor voclosporin, which was assessed in the AURORA trials.  

Dr Merrill discusses how these recently approved medications fit into the standard of care for LN patients. 

--

Joan Merrill, MD, Professor, Department of Medicine, Division of Rheumatology, University of Oklahoma Health Sciences Center; Director of Clinical Projects, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 

Joan Merrill, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a speaker or a member of a speakers bureau for: Biogen 

Received research grant from: Bristol-Myers Squibb; GlaxoSmithKline 

Received income in an amount equal to or greater than $250 from: AbbVie; Alexion; Amgen; AstraZeneca; Aurinia; Bristol-Myers Squibb; EMD Serono; Genentech; Gilead; GlaxoSmithKline; Lilly; Merck; Provention; RemeGen; Sanofi; UCB; Zenas 

Received research grant from: AbbVie; AstraZeneca; BeiGene; Pharmacyclics; TG Therapeutics 

Lupus nephritis (LN) affects approximately 25%-60% of patients with systemic lupus erythematosus. Currently, guideline-directed therapy recommends a combination of steroids plus either mycophenolate mofetil or cyclophosphamide. Despite treatment, about 10%-30% of LN patients will progress to end-stage kidney disease. 

Fortunately, over the past 2 years, the FDA approved two novel agents that expand treatment options for patients with active disease who have received standard-of-care therapy.  

In this ReCAP, Dr Joan Merrill, of the University of Oklahoma Health Sciences Center, reports on the B-lymphocyte stimulator–specific inhibitor belimumab, which was evaluated in the BLISS-LN trial, and the oral calcineurin inhibitor voclosporin, which was assessed in the AURORA trials.  

Dr Merrill discusses how these recently approved medications fit into the standard of care for LN patients. 

--

Joan Merrill, MD, Professor, Department of Medicine, Division of Rheumatology, University of Oklahoma Health Sciences Center; Director of Clinical Projects, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 

Joan Merrill, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a speaker or a member of a speakers bureau for: Biogen 

Received research grant from: Bristol-Myers Squibb; GlaxoSmithKline 

Received income in an amount equal to or greater than $250 from: AbbVie; Alexion; Amgen; AstraZeneca; Aurinia; Bristol-Myers Squibb; EMD Serono; Genentech; Gilead; GlaxoSmithKline; Lilly; Merck; Provention; RemeGen; Sanofi; UCB; Zenas 

Received research grant from: AbbVie; AstraZeneca; BeiGene; Pharmacyclics; TG Therapeutics 

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

The vast majority of children and young people with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 are not hospitalized, according to the most significant global investigation of short-term COVID-19 outcomes in this patient group to date.

In the study, only 1 in 15 (7%) children and young people (younger than 19 years) with RMDs and COVID-19 were hospitalized, and even then, they experienced only mild symptoms; 4 of 5 of those hospitalized did not require supplemental oxygen or ventilatory support.

The study also found that those with severe systemic RMDs and obesity were more likely to be hospitalized than children with juvenile idiopathic arthritis (JIA).

Treatment with biologics, such as tumor necrosis factor inhibitors, did not appear to be associated with more severe COVID-19; however, the study found that children and young people with obesity (body mass index ≥ 30) were more likely to be hospitalized, although only 6% of patients in this study had a BMI in this category. Three patients died – two from areas of lower resources who were diagnosed with systemic lupus erythematosus (SLE) at approximately the same time they were diagnosed with COVID-19, and one with a preexisting autoinflammatory syndrome who was being treated with low-dose glucocorticoids and methotrexate.

Published in Annals of the Rheumatic Diseases, the study was led by Kimme L. Hyrich, MD, PhD, and Lianne Kearsley-Fleet, PhD, both from the University of Manchester (England). Dr. Hyrich is also a consultant rheumatologist at Manchester University Hospitals NHS Foundation Trust.

In an interview, Dr. Hyrich explained that overall these data are reassuring and show that the majority of children and young people with RMDs are not at high risk of severe COVID-19.

“Many parents and families with children who have RMDs have lived with great fear over the pandemic about whether or not their children are at an increased risk of severe COVID-19,” said Dr. Hyrich. “Many are immunosuppressed or take other immunomodulatory medications. This has also had a great impact on schooling and children’s well-being.”

In the study, children with SLE, mixed connective tissue disease (MCTD), or vasculitis were more likely to have severe COVID-19. “[This] is not surprising given the typically greater systemic involvement and need for more aggressive immunosuppressive therapy than the majority of individuals with JIA,” the researchers wrote.

Dr. Hyrich added: “There may be times when children are on particularly high doses of immunosuppression or their disease is particularly active, when they may need more protection, and rheumatology teams can advise parents and young people about this.”

Studies such as those by Zimmerman and Curtis and Viner and colleagues have found that generally, children with no underlying disease are less susceptible to symptomatic COVID-19 and that reports of death are rare. Findings show that the younger the child, the less likely they will be symptomatic.

Adult data suggest a higher risk of COVID-related death among patients with arthritis, lupus, or psoriasis. A recent systematic review of the literature suggested that increased risk of COVID-related death only applies to subgroups of people with RMDs.

However, whether children and young people with RMDs are likely to have more severe COVID-19 and whether there is additional risk attributable to either their underlying disease or its therapy remain unknown. The goal of the study by Dr. Hyrich and colleagues was to address these questions.

The global analysis aimed to describe characteristics of those children and young people (younger than 19 years) with preexisting RMDs who also had COVID-19; to describe outcomes following COVID-19; and to identify characteristics associated with more severe COVID-19 outcomes.

Data were drawn from the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database.

Demographic information included primary RMD diagnosis; RMD disease activity (remission, low, moderate, high, or unknown); RMD treatments, including glucocorticoid use and which disease-modifying antirheumatic drug (DMARD) the patient was taking at the time of COVID-19; and comorbidities (none, ocular inflammation, interstitial lung disease, asthma, diabetes, obesity, hypertension, cerebrovascular accident, renal disease, inflammatory bowel disease, and heart disease).

With respect to COVID-19, information collected included diagnosis date, whether the case was presumptive or confirmed, clinical symptoms, hospitalization and/or death because of COVID-19, and whether the patient stopped receiving rheumatic therapies.

Rheumatology diagnoses were categorized into four groups: JIA; SLE, MCTD, vasculitis, or other RMD; autoinflammatory syndromes; and “other,” including chronic recurrent multifocal osteomyelitis, sarcoidosis, or ocular inflammation.

Of the 607 children and young people with reported SARS-CoV-2 infection from 25 different countries (464 from the EULAR COVID-19 Registry), 499 (82%) cases were polymerase chain reaction confirmed, and 399 (66%) patients were female (median age, 14 years). Most (62%) had JIA: 37%, polyarticular JIA; 30%, oligoarticular JIA; 12%, enthesitis-related JIA; 9%, systemic JIA; 4%, psoriatic JIA; and 9%, JIA of unknown subcategory. Furthermore, 13% of patients had autoinflammatory syndromes, 8% with SLE or MCTD, 3% with vasculitis, and 2% with inflammatory myopathy.

No associations were seen between DMARD treatment (conventional-synthetic, biologic/targeted-synthetic, or combination therapy), compared with no DMARD treatment, glucocorticoid use, and hospitalization.

Owing to substantial differences in reporting of race and ethnicity between data sources, the researchers were unable to analyze whether Black, Asian, and minority ethnic groups with pediatric RMDs are at higher risk of COVID-19–related death, compared with those of White ethnicity, as has been reported for the general population.

The study also did not account for variants of SARS-CoV-2 other than to note that data were collected prior to the spread of the Omicron variant. Also, the registries did not capture vaccination status (though very few children had received vaccines at the time of data collection) or information on long COVID or multisystem inflammatory syndrome in children.

Dr. Hyrich and Dr. Kearsley-Fleet have disclosed no relevant financial relationships.

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

The vast majority of children and young people with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 are not hospitalized, according to the most significant global investigation of short-term COVID-19 outcomes in this patient group to date.

In the study, only 1 in 15 (7%) children and young people (younger than 19 years) with RMDs and COVID-19 were hospitalized, and even then, they experienced only mild symptoms; 4 of 5 of those hospitalized did not require supplemental oxygen or ventilatory support.

The study also found that those with severe systemic RMDs and obesity were more likely to be hospitalized than children with juvenile idiopathic arthritis (JIA).

Treatment with biologics, such as tumor necrosis factor inhibitors, did not appear to be associated with more severe COVID-19; however, the study found that children and young people with obesity (body mass index ≥ 30) were more likely to be hospitalized, although only 6% of patients in this study had a BMI in this category. Three patients died – two from areas of lower resources who were diagnosed with systemic lupus erythematosus (SLE) at approximately the same time they were diagnosed with COVID-19, and one with a preexisting autoinflammatory syndrome who was being treated with low-dose glucocorticoids and methotrexate.

Published in Annals of the Rheumatic Diseases, the study was led by Kimme L. Hyrich, MD, PhD, and Lianne Kearsley-Fleet, PhD, both from the University of Manchester (England). Dr. Hyrich is also a consultant rheumatologist at Manchester University Hospitals NHS Foundation Trust.

In an interview, Dr. Hyrich explained that overall these data are reassuring and show that the majority of children and young people with RMDs are not at high risk of severe COVID-19.

“Many parents and families with children who have RMDs have lived with great fear over the pandemic about whether or not their children are at an increased risk of severe COVID-19,” said Dr. Hyrich. “Many are immunosuppressed or take other immunomodulatory medications. This has also had a great impact on schooling and children’s well-being.”

In the study, children with SLE, mixed connective tissue disease (MCTD), or vasculitis were more likely to have severe COVID-19. “[This] is not surprising given the typically greater systemic involvement and need for more aggressive immunosuppressive therapy than the majority of individuals with JIA,” the researchers wrote.

Dr. Hyrich added: “There may be times when children are on particularly high doses of immunosuppression or their disease is particularly active, when they may need more protection, and rheumatology teams can advise parents and young people about this.”

Studies such as those by Zimmerman and Curtis and Viner and colleagues have found that generally, children with no underlying disease are less susceptible to symptomatic COVID-19 and that reports of death are rare. Findings show that the younger the child, the less likely they will be symptomatic.

Adult data suggest a higher risk of COVID-related death among patients with arthritis, lupus, or psoriasis. A recent systematic review of the literature suggested that increased risk of COVID-related death only applies to subgroups of people with RMDs.

However, whether children and young people with RMDs are likely to have more severe COVID-19 and whether there is additional risk attributable to either their underlying disease or its therapy remain unknown. The goal of the study by Dr. Hyrich and colleagues was to address these questions.

The global analysis aimed to describe characteristics of those children and young people (younger than 19 years) with preexisting RMDs who also had COVID-19; to describe outcomes following COVID-19; and to identify characteristics associated with more severe COVID-19 outcomes.

Data were drawn from the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database.

Demographic information included primary RMD diagnosis; RMD disease activity (remission, low, moderate, high, or unknown); RMD treatments, including glucocorticoid use and which disease-modifying antirheumatic drug (DMARD) the patient was taking at the time of COVID-19; and comorbidities (none, ocular inflammation, interstitial lung disease, asthma, diabetes, obesity, hypertension, cerebrovascular accident, renal disease, inflammatory bowel disease, and heart disease).

With respect to COVID-19, information collected included diagnosis date, whether the case was presumptive or confirmed, clinical symptoms, hospitalization and/or death because of COVID-19, and whether the patient stopped receiving rheumatic therapies.

Rheumatology diagnoses were categorized into four groups: JIA; SLE, MCTD, vasculitis, or other RMD; autoinflammatory syndromes; and “other,” including chronic recurrent multifocal osteomyelitis, sarcoidosis, or ocular inflammation.

Of the 607 children and young people with reported SARS-CoV-2 infection from 25 different countries (464 from the EULAR COVID-19 Registry), 499 (82%) cases were polymerase chain reaction confirmed, and 399 (66%) patients were female (median age, 14 years). Most (62%) had JIA: 37%, polyarticular JIA; 30%, oligoarticular JIA; 12%, enthesitis-related JIA; 9%, systemic JIA; 4%, psoriatic JIA; and 9%, JIA of unknown subcategory. Furthermore, 13% of patients had autoinflammatory syndromes, 8% with SLE or MCTD, 3% with vasculitis, and 2% with inflammatory myopathy.

No associations were seen between DMARD treatment (conventional-synthetic, biologic/targeted-synthetic, or combination therapy), compared with no DMARD treatment, glucocorticoid use, and hospitalization.

Owing to substantial differences in reporting of race and ethnicity between data sources, the researchers were unable to analyze whether Black, Asian, and minority ethnic groups with pediatric RMDs are at higher risk of COVID-19–related death, compared with those of White ethnicity, as has been reported for the general population.

The study also did not account for variants of SARS-CoV-2 other than to note that data were collected prior to the spread of the Omicron variant. Also, the registries did not capture vaccination status (though very few children had received vaccines at the time of data collection) or information on long COVID or multisystem inflammatory syndrome in children.

Dr. Hyrich and Dr. Kearsley-Fleet have disclosed no relevant financial relationships.

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

The vast majority of children and young people with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 are not hospitalized, according to the most significant global investigation of short-term COVID-19 outcomes in this patient group to date.

In the study, only 1 in 15 (7%) children and young people (younger than 19 years) with RMDs and COVID-19 were hospitalized, and even then, they experienced only mild symptoms; 4 of 5 of those hospitalized did not require supplemental oxygen or ventilatory support.

The study also found that those with severe systemic RMDs and obesity were more likely to be hospitalized than children with juvenile idiopathic arthritis (JIA).

Treatment with biologics, such as tumor necrosis factor inhibitors, did not appear to be associated with more severe COVID-19; however, the study found that children and young people with obesity (body mass index ≥ 30) were more likely to be hospitalized, although only 6% of patients in this study had a BMI in this category. Three patients died – two from areas of lower resources who were diagnosed with systemic lupus erythematosus (SLE) at approximately the same time they were diagnosed with COVID-19, and one with a preexisting autoinflammatory syndrome who was being treated with low-dose glucocorticoids and methotrexate.

Published in Annals of the Rheumatic Diseases, the study was led by Kimme L. Hyrich, MD, PhD, and Lianne Kearsley-Fleet, PhD, both from the University of Manchester (England). Dr. Hyrich is also a consultant rheumatologist at Manchester University Hospitals NHS Foundation Trust.

In an interview, Dr. Hyrich explained that overall these data are reassuring and show that the majority of children and young people with RMDs are not at high risk of severe COVID-19.

“Many parents and families with children who have RMDs have lived with great fear over the pandemic about whether or not their children are at an increased risk of severe COVID-19,” said Dr. Hyrich. “Many are immunosuppressed or take other immunomodulatory medications. This has also had a great impact on schooling and children’s well-being.”

In the study, children with SLE, mixed connective tissue disease (MCTD), or vasculitis were more likely to have severe COVID-19. “[This] is not surprising given the typically greater systemic involvement and need for more aggressive immunosuppressive therapy than the majority of individuals with JIA,” the researchers wrote.

Dr. Hyrich added: “There may be times when children are on particularly high doses of immunosuppression or their disease is particularly active, when they may need more protection, and rheumatology teams can advise parents and young people about this.”

Studies such as those by Zimmerman and Curtis and Viner and colleagues have found that generally, children with no underlying disease are less susceptible to symptomatic COVID-19 and that reports of death are rare. Findings show that the younger the child, the less likely they will be symptomatic.

Adult data suggest a higher risk of COVID-related death among patients with arthritis, lupus, or psoriasis. A recent systematic review of the literature suggested that increased risk of COVID-related death only applies to subgroups of people with RMDs.

However, whether children and young people with RMDs are likely to have more severe COVID-19 and whether there is additional risk attributable to either their underlying disease or its therapy remain unknown. The goal of the study by Dr. Hyrich and colleagues was to address these questions.

The global analysis aimed to describe characteristics of those children and young people (younger than 19 years) with preexisting RMDs who also had COVID-19; to describe outcomes following COVID-19; and to identify characteristics associated with more severe COVID-19 outcomes.

Data were drawn from the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database.

Demographic information included primary RMD diagnosis; RMD disease activity (remission, low, moderate, high, or unknown); RMD treatments, including glucocorticoid use and which disease-modifying antirheumatic drug (DMARD) the patient was taking at the time of COVID-19; and comorbidities (none, ocular inflammation, interstitial lung disease, asthma, diabetes, obesity, hypertension, cerebrovascular accident, renal disease, inflammatory bowel disease, and heart disease).

With respect to COVID-19, information collected included diagnosis date, whether the case was presumptive or confirmed, clinical symptoms, hospitalization and/or death because of COVID-19, and whether the patient stopped receiving rheumatic therapies.

Rheumatology diagnoses were categorized into four groups: JIA; SLE, MCTD, vasculitis, or other RMD; autoinflammatory syndromes; and “other,” including chronic recurrent multifocal osteomyelitis, sarcoidosis, or ocular inflammation.

Of the 607 children and young people with reported SARS-CoV-2 infection from 25 different countries (464 from the EULAR COVID-19 Registry), 499 (82%) cases were polymerase chain reaction confirmed, and 399 (66%) patients were female (median age, 14 years). Most (62%) had JIA: 37%, polyarticular JIA; 30%, oligoarticular JIA; 12%, enthesitis-related JIA; 9%, systemic JIA; 4%, psoriatic JIA; and 9%, JIA of unknown subcategory. Furthermore, 13% of patients had autoinflammatory syndromes, 8% with SLE or MCTD, 3% with vasculitis, and 2% with inflammatory myopathy.

No associations were seen between DMARD treatment (conventional-synthetic, biologic/targeted-synthetic, or combination therapy), compared with no DMARD treatment, glucocorticoid use, and hospitalization.

Owing to substantial differences in reporting of race and ethnicity between data sources, the researchers were unable to analyze whether Black, Asian, and minority ethnic groups with pediatric RMDs are at higher risk of COVID-19–related death, compared with those of White ethnicity, as has been reported for the general population.

The study also did not account for variants of SARS-CoV-2 other than to note that data were collected prior to the spread of the Omicron variant. Also, the registries did not capture vaccination status (though very few children had received vaccines at the time of data collection) or information on long COVID or multisystem inflammatory syndrome in children.

Dr. Hyrich and Dr. Kearsley-Fleet have disclosed no relevant financial relationships.

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

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

New recommendations from the European Alliance of Associations for Rheumatology provide both broad and detailed advice for cardiovascular risk management in various rheumatic and musculoskeletal diseases (RMDs), many of which can lead to an increased possibility of cardiovascular disease (CVD).

“The panel believes that these recommendations will enable health care providers and patients to mutually engage in a long-term care pathway tailored to patients’ needs and expectations for improving cardiovascular health in RMDs,” write George C. Drosos, National and Kapodistrian University of Athens, and colleagues. The recommendations were published in February in Annals of the Rheumatic Diseases).

EULAR assembled a task force to generate best practices for preventing CVD in patients with gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren syndrome (SS), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS).

The cardiovascular risk management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis was covered in prior EULAR recommendations.

The task force included 20 members from 11 European countries, including 12 rheumatologists, 2 cardiologists, 1 metabolic medicine physician, 1 health care professional, 2 patient representatives, and 2 EMEUNET (Emerging EULAR Network) members. One group of task force members conducted a systematic literature review of 105 articles about gout, vasculitis, SSc, myositis, MCTD, and SS, and another group evaluated 75 articles about SLE and APS. Together, they decided on four overarching principles:

Clinicians need to be aware of increased cardiovascular risk in patients with RMDs, with disease reduction likely decreasing risk.

Rheumatologists – in tandem with other health care providers – are responsible for their patients’ cardiovascular risk assessment and management.

Screening for cardiovascular risk should be performed regularly in all patients with RMDs, with an emphasis on factors like smoking and blood pressure management.

Patient education and counseling on cardiovascular risk, including important lifestyle modifications, is key for RMD patients.

Specific recommendations from the gout, vasculitis, SSc, myositis, MCTD, and SS group include deploying existing cardiovascular prediction tools as they are used in the general population, with the European Vasculitis Society model suggesting to supplement the Framingham Risk Score for patients with antineutrophil cytoplasmic antibody–associated vasculitis. They also recommended avoiding diuretics in patients with gout and beta-blockers in patients with SSc, as well as following the same blood pressure and lipid management strategies that are used among the general population.

Recommendations from the SLE and APS group include thoroughly assessing traditional cardiovascular risk factors in all patients, following typical blood pressure management strategies in patients with APS, and setting a blood pressure target of less than 130/80 mm Hg in patients with SLE. They also recommended administering the lowest possible glucocorticoid dose in patients with SLE, along with treatment with hydroxychloroquine – unless contraindicated – and even common preventive strategies like low-dose aspirin if it suits their cardiovascular risk profile.

As for next steps, the task force noted several areas where additional focus is needed, such as identifying patient subgroups with increased cardiovascular risk. This could include patients with a longer disease duration or more flare-ups, older patients, and those with certain disease characteristics like antiphospholipid positivity in SLE.

Can EULAR’s recommendations be implemented in U.S. rheumatology practices?

“We have been hearing for years that patients with rheumatic diseases have an increased risk of cardiovascular disease,” Ali A. Duarte Garcia, MD, a rheumatologist at the Mayo Clinic in Rochester, Minn., told this news organization. “That has been consistently published for more than a decade now. But any further guidance about it has not been issued. I think there was a void there.”

“Certainly, cardiovascular disease risk in rheumatoid and psoriatic arthritis has been front of mind for the last decade or so,” Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, said when asked to comment on the recommendations. “But in some of these other conditions, it hasn’t been.”

When asked if rheumatologists would be ready and willing to implement these recommendations, Dr. Duarte Garcia acknowledged that it could be challenging for some.

“It’s a different workflow,” he said. “You’ve been trained traditionally to assess inflammation, to keep the disease under control, which is something they recommend, by the way. If you control the disease, patients do better. But I think lipid screening, for example, and testing for cholesterol, smoking cessation, those well-established programs are harder to bring to a rheumatology clinic. It’s doable, but it’s something that needs to be implemented within the current workflows and could take a few years to take hold.”

Dr. Bartels, however, noted that her group has done extensive work over the last 5 years incorporating certain interventions into practice, including sending patients with high blood pressure back to primary care.

“It’s a sustainable intervention in our clinic that basically our medical assistants and nurses do as a routine operation,” she said. “Our primary care providers are grateful to get these patients back. Our patients are grateful because otherwise when they come to the rheumatologist, get their blood pressure measured, and don’t get feedback, they assume they’re OK. So, we’re giving them a false signal.

“We have a similar intervention with smoking,” she added. “Often our patients aren’t even aware that they’re at increased risk of cardiovascular disease or that smoking might make their rheumatic disease and their cardiovascular outcomes worse. No one has had that conversation with them. They really welcome engaging in those discussions.

“Our tobacco intervention takes 90 seconds at point of care. Our blood pressure intervention at point of care, we’ve timed it, takes 3 minutes. There are ways that we can hardwire this into care.”

Along those lines, Dr. Duarte Garcia stated that the recommendations – although released by EULAR – are largely intuitive and should be very adaptable to an American health care context. He also recognized this moment as an opportunity for rheumatologists to consider patient outcomes beyond what they usually encounter firsthand.

“I don’t think we have many rheumatologists with patients who get a stroke or heart attack because if that happens, it’s in a hospital context or they go see a cardiologist,” he said. “You may see it once it happens if they survive and come and see you – or perhaps if you’re in a more integrated practice – but I don’t think it’s as apparent in our clinics because it is a predominantly outpatient practice and many times those are emergencies or inpatient complications.

“The bottom line,” he added, “is these are practical guidelines. It’s a push in the right direction, but there is still work to be done. And hopefully some of the recommendations, like measuring high blood pressure and addressing it just as in the general population, are something we can start to implement.”

Dr. Duarte Garcia reported receiving grant funding from the Rheumatology Research Foundation and the Centers for Disease Control and Prevention. Dr. Bartels reported that her group’s tobacco cessation work is funded by Pfizer’s Independent Grants for Learning and Change.

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

New recommendations from the European Alliance of Associations for Rheumatology provide both broad and detailed advice for cardiovascular risk management in various rheumatic and musculoskeletal diseases (RMDs), many of which can lead to an increased possibility of cardiovascular disease (CVD).

“The panel believes that these recommendations will enable health care providers and patients to mutually engage in a long-term care pathway tailored to patients’ needs and expectations for improving cardiovascular health in RMDs,” write George C. Drosos, National and Kapodistrian University of Athens, and colleagues. The recommendations were published in February in Annals of the Rheumatic Diseases).

EULAR assembled a task force to generate best practices for preventing CVD in patients with gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren syndrome (SS), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS).

The cardiovascular risk management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis was covered in prior EULAR recommendations.

The task force included 20 members from 11 European countries, including 12 rheumatologists, 2 cardiologists, 1 metabolic medicine physician, 1 health care professional, 2 patient representatives, and 2 EMEUNET (Emerging EULAR Network) members. One group of task force members conducted a systematic literature review of 105 articles about gout, vasculitis, SSc, myositis, MCTD, and SS, and another group evaluated 75 articles about SLE and APS. Together, they decided on four overarching principles:

Clinicians need to be aware of increased cardiovascular risk in patients with RMDs, with disease reduction likely decreasing risk.

Rheumatologists – in tandem with other health care providers – are responsible for their patients’ cardiovascular risk assessment and management.

Screening for cardiovascular risk should be performed regularly in all patients with RMDs, with an emphasis on factors like smoking and blood pressure management.

Patient education and counseling on cardiovascular risk, including important lifestyle modifications, is key for RMD patients.

Specific recommendations from the gout, vasculitis, SSc, myositis, MCTD, and SS group include deploying existing cardiovascular prediction tools as they are used in the general population, with the European Vasculitis Society model suggesting to supplement the Framingham Risk Score for patients with antineutrophil cytoplasmic antibody–associated vasculitis. They also recommended avoiding diuretics in patients with gout and beta-blockers in patients with SSc, as well as following the same blood pressure and lipid management strategies that are used among the general population.

Recommendations from the SLE and APS group include thoroughly assessing traditional cardiovascular risk factors in all patients, following typical blood pressure management strategies in patients with APS, and setting a blood pressure target of less than 130/80 mm Hg in patients with SLE. They also recommended administering the lowest possible glucocorticoid dose in patients with SLE, along with treatment with hydroxychloroquine – unless contraindicated – and even common preventive strategies like low-dose aspirin if it suits their cardiovascular risk profile.

As for next steps, the task force noted several areas where additional focus is needed, such as identifying patient subgroups with increased cardiovascular risk. This could include patients with a longer disease duration or more flare-ups, older patients, and those with certain disease characteristics like antiphospholipid positivity in SLE.

Can EULAR’s recommendations be implemented in U.S. rheumatology practices?

“We have been hearing for years that patients with rheumatic diseases have an increased risk of cardiovascular disease,” Ali A. Duarte Garcia, MD, a rheumatologist at the Mayo Clinic in Rochester, Minn., told this news organization. “That has been consistently published for more than a decade now. But any further guidance about it has not been issued. I think there was a void there.”

“Certainly, cardiovascular disease risk in rheumatoid and psoriatic arthritis has been front of mind for the last decade or so,” Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, said when asked to comment on the recommendations. “But in some of these other conditions, it hasn’t been.”

When asked if rheumatologists would be ready and willing to implement these recommendations, Dr. Duarte Garcia acknowledged that it could be challenging for some.

“It’s a different workflow,” he said. “You’ve been trained traditionally to assess inflammation, to keep the disease under control, which is something they recommend, by the way. If you control the disease, patients do better. But I think lipid screening, for example, and testing for cholesterol, smoking cessation, those well-established programs are harder to bring to a rheumatology clinic. It’s doable, but it’s something that needs to be implemented within the current workflows and could take a few years to take hold.”

Dr. Bartels, however, noted that her group has done extensive work over the last 5 years incorporating certain interventions into practice, including sending patients with high blood pressure back to primary care.

“It’s a sustainable intervention in our clinic that basically our medical assistants and nurses do as a routine operation,” she said. “Our primary care providers are grateful to get these patients back. Our patients are grateful because otherwise when they come to the rheumatologist, get their blood pressure measured, and don’t get feedback, they assume they’re OK. So, we’re giving them a false signal.

“We have a similar intervention with smoking,” she added. “Often our patients aren’t even aware that they’re at increased risk of cardiovascular disease or that smoking might make their rheumatic disease and their cardiovascular outcomes worse. No one has had that conversation with them. They really welcome engaging in those discussions.

“Our tobacco intervention takes 90 seconds at point of care. Our blood pressure intervention at point of care, we’ve timed it, takes 3 minutes. There are ways that we can hardwire this into care.”

Along those lines, Dr. Duarte Garcia stated that the recommendations – although released by EULAR – are largely intuitive and should be very adaptable to an American health care context. He also recognized this moment as an opportunity for rheumatologists to consider patient outcomes beyond what they usually encounter firsthand.

“I don’t think we have many rheumatologists with patients who get a stroke or heart attack because if that happens, it’s in a hospital context or they go see a cardiologist,” he said. “You may see it once it happens if they survive and come and see you – or perhaps if you’re in a more integrated practice – but I don’t think it’s as apparent in our clinics because it is a predominantly outpatient practice and many times those are emergencies or inpatient complications.

“The bottom line,” he added, “is these are practical guidelines. It’s a push in the right direction, but there is still work to be done. And hopefully some of the recommendations, like measuring high blood pressure and addressing it just as in the general population, are something we can start to implement.”

Dr. Duarte Garcia reported receiving grant funding from the Rheumatology Research Foundation and the Centers for Disease Control and Prevention. Dr. Bartels reported that her group’s tobacco cessation work is funded by Pfizer’s Independent Grants for Learning and Change.

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

New recommendations from the European Alliance of Associations for Rheumatology provide both broad and detailed advice for cardiovascular risk management in various rheumatic and musculoskeletal diseases (RMDs), many of which can lead to an increased possibility of cardiovascular disease (CVD).

“The panel believes that these recommendations will enable health care providers and patients to mutually engage in a long-term care pathway tailored to patients’ needs and expectations for improving cardiovascular health in RMDs,” write George C. Drosos, National and Kapodistrian University of Athens, and colleagues. The recommendations were published in February in Annals of the Rheumatic Diseases).

EULAR assembled a task force to generate best practices for preventing CVD in patients with gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren syndrome (SS), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS).

The cardiovascular risk management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis was covered in prior EULAR recommendations.

The task force included 20 members from 11 European countries, including 12 rheumatologists, 2 cardiologists, 1 metabolic medicine physician, 1 health care professional, 2 patient representatives, and 2 EMEUNET (Emerging EULAR Network) members. One group of task force members conducted a systematic literature review of 105 articles about gout, vasculitis, SSc, myositis, MCTD, and SS, and another group evaluated 75 articles about SLE and APS. Together, they decided on four overarching principles:

Clinicians need to be aware of increased cardiovascular risk in patients with RMDs, with disease reduction likely decreasing risk.

Rheumatologists – in tandem with other health care providers – are responsible for their patients’ cardiovascular risk assessment and management.

Screening for cardiovascular risk should be performed regularly in all patients with RMDs, with an emphasis on factors like smoking and blood pressure management.

Patient education and counseling on cardiovascular risk, including important lifestyle modifications, is key for RMD patients.

Specific recommendations from the gout, vasculitis, SSc, myositis, MCTD, and SS group include deploying existing cardiovascular prediction tools as they are used in the general population, with the European Vasculitis Society model suggesting to supplement the Framingham Risk Score for patients with antineutrophil cytoplasmic antibody–associated vasculitis. They also recommended avoiding diuretics in patients with gout and beta-blockers in patients with SSc, as well as following the same blood pressure and lipid management strategies that are used among the general population.

Recommendations from the SLE and APS group include thoroughly assessing traditional cardiovascular risk factors in all patients, following typical blood pressure management strategies in patients with APS, and setting a blood pressure target of less than 130/80 mm Hg in patients with SLE. They also recommended administering the lowest possible glucocorticoid dose in patients with SLE, along with treatment with hydroxychloroquine – unless contraindicated – and even common preventive strategies like low-dose aspirin if it suits their cardiovascular risk profile.

As for next steps, the task force noted several areas where additional focus is needed, such as identifying patient subgroups with increased cardiovascular risk. This could include patients with a longer disease duration or more flare-ups, older patients, and those with certain disease characteristics like antiphospholipid positivity in SLE.

Can EULAR’s recommendations be implemented in U.S. rheumatology practices?

“We have been hearing for years that patients with rheumatic diseases have an increased risk of cardiovascular disease,” Ali A. Duarte Garcia, MD, a rheumatologist at the Mayo Clinic in Rochester, Minn., told this news organization. “That has been consistently published for more than a decade now. But any further guidance about it has not been issued. I think there was a void there.”

“Certainly, cardiovascular disease risk in rheumatoid and psoriatic arthritis has been front of mind for the last decade or so,” Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison, said when asked to comment on the recommendations. “But in some of these other conditions, it hasn’t been.”

When asked if rheumatologists would be ready and willing to implement these recommendations, Dr. Duarte Garcia acknowledged that it could be challenging for some.

“It’s a different workflow,” he said. “You’ve been trained traditionally to assess inflammation, to keep the disease under control, which is something they recommend, by the way. If you control the disease, patients do better. But I think lipid screening, for example, and testing for cholesterol, smoking cessation, those well-established programs are harder to bring to a rheumatology clinic. It’s doable, but it’s something that needs to be implemented within the current workflows and could take a few years to take hold.”

Dr. Bartels, however, noted that her group has done extensive work over the last 5 years incorporating certain interventions into practice, including sending patients with high blood pressure back to primary care.

“It’s a sustainable intervention in our clinic that basically our medical assistants and nurses do as a routine operation,” she said. “Our primary care providers are grateful to get these patients back. Our patients are grateful because otherwise when they come to the rheumatologist, get their blood pressure measured, and don’t get feedback, they assume they’re OK. So, we’re giving them a false signal.

“We have a similar intervention with smoking,” she added. “Often our patients aren’t even aware that they’re at increased risk of cardiovascular disease or that smoking might make their rheumatic disease and their cardiovascular outcomes worse. No one has had that conversation with them. They really welcome engaging in those discussions.

“Our tobacco intervention takes 90 seconds at point of care. Our blood pressure intervention at point of care, we’ve timed it, takes 3 minutes. There are ways that we can hardwire this into care.”

Along those lines, Dr. Duarte Garcia stated that the recommendations – although released by EULAR – are largely intuitive and should be very adaptable to an American health care context. He also recognized this moment as an opportunity for rheumatologists to consider patient outcomes beyond what they usually encounter firsthand.

“I don’t think we have many rheumatologists with patients who get a stroke or heart attack because if that happens, it’s in a hospital context or they go see a cardiologist,” he said. “You may see it once it happens if they survive and come and see you – or perhaps if you’re in a more integrated practice – but I don’t think it’s as apparent in our clinics because it is a predominantly outpatient practice and many times those are emergencies or inpatient complications.

“The bottom line,” he added, “is these are practical guidelines. It’s a push in the right direction, but there is still work to be done. And hopefully some of the recommendations, like measuring high blood pressure and addressing it just as in the general population, are something we can start to implement.”

Dr. Duarte Garcia reported receiving grant funding from the Rheumatology Research Foundation and the Centers for Disease Control and Prevention. Dr. Bartels reported that her group’s tobacco cessation work is funded by Pfizer’s Independent Grants for Learning and Change.

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

New prescriptions of hydroxychloroquine (HCQ) and ivermectin increased in 2020, driven particularly by rates in counties with the highest proportion of Republican votes in the 2020 U.S. presidential election, according to a cross-sectional study published in JAMA Internal Medicine.

“Our findings are consistent with the hypothesis that U.S. prescribing of hydroxychloroquine and ivermectin during the COVID-19 pandemic may have been influenced by political affiliation,” wrote Michael L. Barnett, MD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.
 

The researchers used data from the OptumLabs Data Warehouse to analyze commercial and Medicare Advantage medical claims from January 2019 through December 2020 for more than 18.5 million adults living in counties with at least 50 enrollees.

Marc Bruxelle/Getty Images

The Food and Drug Administration issued an emergency use authorization (EUA) for HCQ as a COVID-19 treatment on March 28, 2020, but the agency revoked the EUA 3 months later on June 15. Ivermectin never received an EUA for COVID treatment, but an in vitro study published April 3, 2020 claimed it had an antiviral effect.

The National Institutes of Health recommended against using ivermectin as a COVID-19 treatment on Aug. 1, 2020, but a few months later, on Nov. 13, a flawed clinical trial – later retracted – claimed ivermectin was 90% effective in treating COVID-19. Despite the lack of evidence for ivermectin’s efficacy, a Senate committee meeting on Dec. 8, 2020, included testimony from a physician who promoted its use.

Mario Olaya/Pixabay

In comparing ivermectin and HCQ prescription rates with counties’ political composition, the researchers adjusted their findings to account for differences in the counties’ racial composition and COVID-19 incidence as well as enrollees’ age, sex, insurance type, income, comorbidity burden, and home in a rural or urban area.

The results showed an average of 20 new HCQ prescriptions per 100,000 enrollees in 2019, but 2020 saw a sharp increase and drop in new HCQ prescriptions in March-April 2020, independent of counties’ breakdown of political affiliation.

“However, after June 2020, coinciding with the revocation of the U.S. Food and Drug Administration’s emergency use authorization for hydroxychloroquine, prescribing volume was significantly higher in the highest vs. lowest Republican vote share counties,” the authors report. The gradual increase from June through December 2020 averaged to 42 new prescriptions per 100,000, a 146% increase over 2019 rates that was driven largely by the 25% of counties with the highest proportion of Republican voters.

Similarly, rates of new ivermectin prescriptions in December 2020 were more than nine times higher in counties with the highest Republican vote share, compared with new prescriptions throughout 2019. The researchers found no differences in new prescriptions for methotrexate or albendazole in 2020 based on counties’ proportion of Republican votes.

Since the study is an ecological, observational one, it cannot show causation or shed light on what role patients, physicians, or other factors might have played in prescribing patterns. Nevertheless, the authors noted the potentially negative implications of their findings.

“Because political affiliation should not be a factor in clinical treatment decisions, our findings raise concerns for public trust in a nonpartisan health care system,” the authors write.

Coauthor Ateev Mehrotra, MD, MPH, reported personal fees from Sanofi-Aventis, and coauthor Anupam B. Jena, MD, PhD, reported personal fees from Bioverativ, Merck, Janssen, Edwards Lifesciences, Novartis, Amgen, Eisai, Otsuka, Vertex, Celgene, Sanofi-Aventis, Precision Health Economics (now PRECISIONheor), Analysis Group, and Doubleday and hosting the podcast Freakonomics, M.D. The other coauthors have disclosed no relevant financial relationships. No external funding source was noted.

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

New prescriptions of hydroxychloroquine (HCQ) and ivermectin increased in 2020, driven particularly by rates in counties with the highest proportion of Republican votes in the 2020 U.S. presidential election, according to a cross-sectional study published in JAMA Internal Medicine.

“Our findings are consistent with the hypothesis that U.S. prescribing of hydroxychloroquine and ivermectin during the COVID-19 pandemic may have been influenced by political affiliation,” wrote Michael L. Barnett, MD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.
 

The researchers used data from the OptumLabs Data Warehouse to analyze commercial and Medicare Advantage medical claims from January 2019 through December 2020 for more than 18.5 million adults living in counties with at least 50 enrollees.

Marc Bruxelle/Getty Images

The Food and Drug Administration issued an emergency use authorization (EUA) for HCQ as a COVID-19 treatment on March 28, 2020, but the agency revoked the EUA 3 months later on June 15. Ivermectin never received an EUA for COVID treatment, but an in vitro study published April 3, 2020 claimed it had an antiviral effect.

The National Institutes of Health recommended against using ivermectin as a COVID-19 treatment on Aug. 1, 2020, but a few months later, on Nov. 13, a flawed clinical trial – later retracted – claimed ivermectin was 90% effective in treating COVID-19. Despite the lack of evidence for ivermectin’s efficacy, a Senate committee meeting on Dec. 8, 2020, included testimony from a physician who promoted its use.

Mario Olaya/Pixabay

In comparing ivermectin and HCQ prescription rates with counties’ political composition, the researchers adjusted their findings to account for differences in the counties’ racial composition and COVID-19 incidence as well as enrollees’ age, sex, insurance type, income, comorbidity burden, and home in a rural or urban area.

The results showed an average of 20 new HCQ prescriptions per 100,000 enrollees in 2019, but 2020 saw a sharp increase and drop in new HCQ prescriptions in March-April 2020, independent of counties’ breakdown of political affiliation.

“However, after June 2020, coinciding with the revocation of the U.S. Food and Drug Administration’s emergency use authorization for hydroxychloroquine, prescribing volume was significantly higher in the highest vs. lowest Republican vote share counties,” the authors report. The gradual increase from June through December 2020 averaged to 42 new prescriptions per 100,000, a 146% increase over 2019 rates that was driven largely by the 25% of counties with the highest proportion of Republican voters.

Similarly, rates of new ivermectin prescriptions in December 2020 were more than nine times higher in counties with the highest Republican vote share, compared with new prescriptions throughout 2019. The researchers found no differences in new prescriptions for methotrexate or albendazole in 2020 based on counties’ proportion of Republican votes.

Since the study is an ecological, observational one, it cannot show causation or shed light on what role patients, physicians, or other factors might have played in prescribing patterns. Nevertheless, the authors noted the potentially negative implications of their findings.

“Because political affiliation should not be a factor in clinical treatment decisions, our findings raise concerns for public trust in a nonpartisan health care system,” the authors write.

Coauthor Ateev Mehrotra, MD, MPH, reported personal fees from Sanofi-Aventis, and coauthor Anupam B. Jena, MD, PhD, reported personal fees from Bioverativ, Merck, Janssen, Edwards Lifesciences, Novartis, Amgen, Eisai, Otsuka, Vertex, Celgene, Sanofi-Aventis, Precision Health Economics (now PRECISIONheor), Analysis Group, and Doubleday and hosting the podcast Freakonomics, M.D. The other coauthors have disclosed no relevant financial relationships. No external funding source was noted.

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

New prescriptions of hydroxychloroquine (HCQ) and ivermectin increased in 2020, driven particularly by rates in counties with the highest proportion of Republican votes in the 2020 U.S. presidential election, according to a cross-sectional study published in JAMA Internal Medicine.

“Our findings are consistent with the hypothesis that U.S. prescribing of hydroxychloroquine and ivermectin during the COVID-19 pandemic may have been influenced by political affiliation,” wrote Michael L. Barnett, MD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.
 

The researchers used data from the OptumLabs Data Warehouse to analyze commercial and Medicare Advantage medical claims from January 2019 through December 2020 for more than 18.5 million adults living in counties with at least 50 enrollees.

Marc Bruxelle/Getty Images

The Food and Drug Administration issued an emergency use authorization (EUA) for HCQ as a COVID-19 treatment on March 28, 2020, but the agency revoked the EUA 3 months later on June 15. Ivermectin never received an EUA for COVID treatment, but an in vitro study published April 3, 2020 claimed it had an antiviral effect.

The National Institutes of Health recommended against using ivermectin as a COVID-19 treatment on Aug. 1, 2020, but a few months later, on Nov. 13, a flawed clinical trial – later retracted – claimed ivermectin was 90% effective in treating COVID-19. Despite the lack of evidence for ivermectin’s efficacy, a Senate committee meeting on Dec. 8, 2020, included testimony from a physician who promoted its use.

Mario Olaya/Pixabay

In comparing ivermectin and HCQ prescription rates with counties’ political composition, the researchers adjusted their findings to account for differences in the counties’ racial composition and COVID-19 incidence as well as enrollees’ age, sex, insurance type, income, comorbidity burden, and home in a rural or urban area.

The results showed an average of 20 new HCQ prescriptions per 100,000 enrollees in 2019, but 2020 saw a sharp increase and drop in new HCQ prescriptions in March-April 2020, independent of counties’ breakdown of political affiliation.

“However, after June 2020, coinciding with the revocation of the U.S. Food and Drug Administration’s emergency use authorization for hydroxychloroquine, prescribing volume was significantly higher in the highest vs. lowest Republican vote share counties,” the authors report. The gradual increase from June through December 2020 averaged to 42 new prescriptions per 100,000, a 146% increase over 2019 rates that was driven largely by the 25% of counties with the highest proportion of Republican voters.

Similarly, rates of new ivermectin prescriptions in December 2020 were more than nine times higher in counties with the highest Republican vote share, compared with new prescriptions throughout 2019. The researchers found no differences in new prescriptions for methotrexate or albendazole in 2020 based on counties’ proportion of Republican votes.

Since the study is an ecological, observational one, it cannot show causation or shed light on what role patients, physicians, or other factors might have played in prescribing patterns. Nevertheless, the authors noted the potentially negative implications of their findings.

“Because political affiliation should not be a factor in clinical treatment decisions, our findings raise concerns for public trust in a nonpartisan health care system,” the authors write.

Coauthor Ateev Mehrotra, MD, MPH, reported personal fees from Sanofi-Aventis, and coauthor Anupam B. Jena, MD, PhD, reported personal fees from Bioverativ, Merck, Janssen, Edwards Lifesciences, Novartis, Amgen, Eisai, Otsuka, Vertex, Celgene, Sanofi-Aventis, Precision Health Economics (now PRECISIONheor), Analysis Group, and Doubleday and hosting the podcast Freakonomics, M.D. The other coauthors have disclosed no relevant financial relationships. No external funding source was noted.

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

The COVID-19 pandemic led to a decrease in the proportion of patients with rheumatic diseases who stopped taking their disease-modifying antirheumatic drugs (DMARDs), but the percentage who interrupted DMARD treatment increased later in the pandemic, according to speakers at the 2022 Rheumatology Winter Clinical Symposium.

“People seem to be less anxious, but they’re interrupting their DMARD therapy more, more recently than in the pits of COVID, if you will,” said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, and director of RWCS.

RWCS 2022 screenshot

Dr. Kavanaugh and his copresenter Jack Cush, MD, were discussing the results of a recent study published in Arthritis Care & Research that evaluated 2,424 patients with rheumatic diseases who completed a baseline and at least one follow-up survey issued by patient organizations between March 2020 and May 2021, with a median of five follow-up surveys completed. The patients included in the study were aged a mean of 57 years, 86.6% were women, 90.5% were White, 41.8% had rheumatoid arthritis (RA), 14.8% had antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and 12.4% had psoriatic arthritis. Overall, 52.6% were on biologics or a Janus kinase (JAK) inhibitor, 30.0% were receiving methotrexate, 21.4% were taking hydroxychloroquine, and 28.6% were receiving low-dose (24.0%) or high-dose (4.6%) glucocorticoids.

Patients’ T-scores on the anxiety short form Patient-Reported Outcomes Measurement Information System (PROMIS) survey significantly decreased from a score of 58.7 in April 2020 to a score of 53.7 in May 2021 (P < .001), but there was a significant decrease in the interruption of DMARD treatment between April and December 2020 (11.2% vs. 7.5%; P < .001). This percentage rose significantly to 14.0% by May 2021 (P < .001). Patients who stopped using DMARDs were significantly associated with predicted incidence of severe flare in the next survey in adjusted models (12.9% vs. 8.0%; odds ratio, 1.71; 95% confidence interval, 1.23-2.36).

The results tell us “that we as a discipline are not doing a good job educating our patients,” said Dr. Cush, a rheumatologist based in Dallas, Tex., and executive editor of RheumNow.com.

“I wish we – and I’m really talking about myself – but myself and my practice were more proactive when COVID happened [in] sending out regular bulletins: ‘Don’t stop your therapy; these are the things you get; get the test that you need to get done,’ ” he said. “We let a lot of things go on autopilot with the patient driving throughout COVID. Even now, it’s happening. And this is a problem, and there are going to be consequences to this.”

Dr. Kavanaugh agreed with Dr. Cush’s assessment, suggesting that the pandemic came up quickly enough that it was difficult to be proactive with the situation.
 

Patients on JAK inhibitors as new COVID-19 risk group?

Another standout study on COVID-19 from 2021 was an analysis of the COVID-19 Global Rheumatology Alliance physician registry that examined risk of COVID-19 severity for patients with RA taking biologic or targeted synthetic DMARDs (tsDMARDs), which was presented at the 2021 EULAR congress and later published in Annals of the Rheumatic Diseases.

The researchers evaluated 2,869 patients March 2020 and April 2021 who were receiving abatacept (237 patients), rituximab (364 patients), interleukin (IL)-6 inhibitors (317 patients), JAK inhibitors (563 patients), or tumor necrosis factor (TNF) inhibitors such as infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab (1,388 patients) before developing COVID-19. Data about biologics or tsDMARDs were collected as a drug class. Patients in the study were mostly White (69.0%) women (80.8%) with a mean age of 56.7 years who lived in Europe (51.8%) or North America (35.0%). The researchers examined the severity of COVID-19 among all patients studied and calculated odds ratios based on drug class, with the TNF inhibitor group serving as a reference.

“[I]n this case, they said that the baseline use of rituximab was associated with more severity, and you see the severity being hospitalization and ICU and deaths. They found a signal for the JAK inhibitors that is not found in the other studies,” Dr. Kavanaugh said.

Overall, they found 21% of patients in the registry were hospitalized and 5.5% died, with rituximab (OR, 4.15; 95% CI, 3.16-5.44) and JAK inhibitors (OR, 2.06; 95% CI, 1.60-2.65) associated with more severe COVID-19 outcomes. Specifically, rituximab was associated with greater likelihood of hospitalization (OR, 4.53; 95% CI, 3.32-6.18), hospitalization with oxygen/ventilation (OR, 2.87; 95% CI, 2.03-4.06), need for mechanical ventilation (OR, 4.05; 95% CI, 3.08-5.33), and mortality (OR, 4.57; 95% CI, 3.32-9.01), compared with TNF inhibitors. For JAK inhibitors, there was also a greater likelihood of hospitalization (OR, 2.40; 95% CI, 1.78-3.24), hospitalization with oxygen/ventilation (OR, 1.55; 95% CI, 1.04-2.18), need for mechanical ventilation (OR, 2.03; 95% CI, 1.56-2.62), and mortality (OR, 2.04; 95% CI, 1.58-2.65), compared with the TNF inhibitors group. Associations between COVID-19 severity and abatacept or IL-6 inhibitors were not identified.

Commenting on the study in a question-and-answer session, Roy Fleischmann, MD, said the part of the study that identified a signal for JAK inhibitors was “very interesting.” He called attention to a rapid response comment to the study, which questioned if it was the drug class itself that caused the risk for severe disease. “This is very important, because actually, the patients who stop the JAK [inhibitor], that’s what drove the illness. The patients [who] continued the JAK [inhibitor], very few of them had illness,” said Dr. Fleischmann, clinical professor of medicine at the University of Texas Southwestern Medical School and codirector of the Metroplex Clinical Research Center, both in Dallas, Tex.
 

Confusion among patients during COVID-19

Alvin Wells, MD, PhD, asked the copresenters during the Q&A session whether they had any clinical pearls for the audience on how they manage treatment of patients with rheumatic disease with potential COVID-19 risk. “I think the confusion with our patients and COVID is what the ACR has put out with their guidelines,” said Dr. Wells, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc.

Dr. Cush said he has three rules he follows: lower and discontinue steroids, avoid rituximab as a starting treatment and negotiate if patients are already taking it, and don’t stop any therapy.

“I want disease control. I think being under control is what keeps you away from risk of COVID and hospitalization,” Dr. Cush said. “I think being uncontrolled and inflamed, whether it’s our [patients with] inflammatory arthritis or lupus or, worse, vasculitis [or] myositis, those are the ones at high risk of progression from being just infected to being sick and in the hospital.”

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, posed the question of getting somewhat back to normal during COVID-19 with regard to recently infected patients presenting at infusion centers, whether patients are more likely to continue testing positive, and when patients are cleared to come back. Dr. Ruderman said his center has a 20-day rule for returning after having COVID-19, while Dr. Cush said his center allows patients to come in if they test negative after 7-10 days.

“One of the things we’re struggling with is our infusion center, and one of the questions that keeps coming up is when can people come back after a COVID infection?” he said. “If you’re on a drug at home, that’s up to you and the patient. But in the infusion [center], then you have other people sitting around there.”

Dr. Kavanaugh said there is no current data for how long patients with rheumatic disease shed virus, or how long a positive test can be measured. “You definitely will continue to shed, and you’ll be detectable for a while,” he said.

Dr. Cush and Dr. Kavanaugh reported having financial relationships with numerous pharmaceutical companies.

The COVID-19 pandemic led to a decrease in the proportion of patients with rheumatic diseases who stopped taking their disease-modifying antirheumatic drugs (DMARDs), but the percentage who interrupted DMARD treatment increased later in the pandemic, according to speakers at the 2022 Rheumatology Winter Clinical Symposium.

“People seem to be less anxious, but they’re interrupting their DMARD therapy more, more recently than in the pits of COVID, if you will,” said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, and director of RWCS.

RWCS 2022 screenshot

Dr. Kavanaugh and his copresenter Jack Cush, MD, were discussing the results of a recent study published in Arthritis Care & Research that evaluated 2,424 patients with rheumatic diseases who completed a baseline and at least one follow-up survey issued by patient organizations between March 2020 and May 2021, with a median of five follow-up surveys completed. The patients included in the study were aged a mean of 57 years, 86.6% were women, 90.5% were White, 41.8% had rheumatoid arthritis (RA), 14.8% had antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and 12.4% had psoriatic arthritis. Overall, 52.6% were on biologics or a Janus kinase (JAK) inhibitor, 30.0% were receiving methotrexate, 21.4% were taking hydroxychloroquine, and 28.6% were receiving low-dose (24.0%) or high-dose (4.6%) glucocorticoids.

Patients’ T-scores on the anxiety short form Patient-Reported Outcomes Measurement Information System (PROMIS) survey significantly decreased from a score of 58.7 in April 2020 to a score of 53.7 in May 2021 (P < .001), but there was a significant decrease in the interruption of DMARD treatment between April and December 2020 (11.2% vs. 7.5%; P < .001). This percentage rose significantly to 14.0% by May 2021 (P < .001). Patients who stopped using DMARDs were significantly associated with predicted incidence of severe flare in the next survey in adjusted models (12.9% vs. 8.0%; odds ratio, 1.71; 95% confidence interval, 1.23-2.36).

The results tell us “that we as a discipline are not doing a good job educating our patients,” said Dr. Cush, a rheumatologist based in Dallas, Tex., and executive editor of RheumNow.com.

“I wish we – and I’m really talking about myself – but myself and my practice were more proactive when COVID happened [in] sending out regular bulletins: ‘Don’t stop your therapy; these are the things you get; get the test that you need to get done,’ ” he said. “We let a lot of things go on autopilot with the patient driving throughout COVID. Even now, it’s happening. And this is a problem, and there are going to be consequences to this.”

Dr. Kavanaugh agreed with Dr. Cush’s assessment, suggesting that the pandemic came up quickly enough that it was difficult to be proactive with the situation.
 

Patients on JAK inhibitors as new COVID-19 risk group?

Another standout study on COVID-19 from 2021 was an analysis of the COVID-19 Global Rheumatology Alliance physician registry that examined risk of COVID-19 severity for patients with RA taking biologic or targeted synthetic DMARDs (tsDMARDs), which was presented at the 2021 EULAR congress and later published in Annals of the Rheumatic Diseases.

The researchers evaluated 2,869 patients March 2020 and April 2021 who were receiving abatacept (237 patients), rituximab (364 patients), interleukin (IL)-6 inhibitors (317 patients), JAK inhibitors (563 patients), or tumor necrosis factor (TNF) inhibitors such as infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab (1,388 patients) before developing COVID-19. Data about biologics or tsDMARDs were collected as a drug class. Patients in the study were mostly White (69.0%) women (80.8%) with a mean age of 56.7 years who lived in Europe (51.8%) or North America (35.0%). The researchers examined the severity of COVID-19 among all patients studied and calculated odds ratios based on drug class, with the TNF inhibitor group serving as a reference.

“[I]n this case, they said that the baseline use of rituximab was associated with more severity, and you see the severity being hospitalization and ICU and deaths. They found a signal for the JAK inhibitors that is not found in the other studies,” Dr. Kavanaugh said.

Overall, they found 21% of patients in the registry were hospitalized and 5.5% died, with rituximab (OR, 4.15; 95% CI, 3.16-5.44) and JAK inhibitors (OR, 2.06; 95% CI, 1.60-2.65) associated with more severe COVID-19 outcomes. Specifically, rituximab was associated with greater likelihood of hospitalization (OR, 4.53; 95% CI, 3.32-6.18), hospitalization with oxygen/ventilation (OR, 2.87; 95% CI, 2.03-4.06), need for mechanical ventilation (OR, 4.05; 95% CI, 3.08-5.33), and mortality (OR, 4.57; 95% CI, 3.32-9.01), compared with TNF inhibitors. For JAK inhibitors, there was also a greater likelihood of hospitalization (OR, 2.40; 95% CI, 1.78-3.24), hospitalization with oxygen/ventilation (OR, 1.55; 95% CI, 1.04-2.18), need for mechanical ventilation (OR, 2.03; 95% CI, 1.56-2.62), and mortality (OR, 2.04; 95% CI, 1.58-2.65), compared with the TNF inhibitors group. Associations between COVID-19 severity and abatacept or IL-6 inhibitors were not identified.

Commenting on the study in a question-and-answer session, Roy Fleischmann, MD, said the part of the study that identified a signal for JAK inhibitors was “very interesting.” He called attention to a rapid response comment to the study, which questioned if it was the drug class itself that caused the risk for severe disease. “This is very important, because actually, the patients who stop the JAK [inhibitor], that’s what drove the illness. The patients [who] continued the JAK [inhibitor], very few of them had illness,” said Dr. Fleischmann, clinical professor of medicine at the University of Texas Southwestern Medical School and codirector of the Metroplex Clinical Research Center, both in Dallas, Tex.
 

Confusion among patients during COVID-19

Alvin Wells, MD, PhD, asked the copresenters during the Q&A session whether they had any clinical pearls for the audience on how they manage treatment of patients with rheumatic disease with potential COVID-19 risk. “I think the confusion with our patients and COVID is what the ACR has put out with their guidelines,” said Dr. Wells, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc.

Dr. Cush said he has three rules he follows: lower and discontinue steroids, avoid rituximab as a starting treatment and negotiate if patients are already taking it, and don’t stop any therapy.

“I want disease control. I think being under control is what keeps you away from risk of COVID and hospitalization,” Dr. Cush said. “I think being uncontrolled and inflamed, whether it’s our [patients with] inflammatory arthritis or lupus or, worse, vasculitis [or] myositis, those are the ones at high risk of progression from being just infected to being sick and in the hospital.”

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, posed the question of getting somewhat back to normal during COVID-19 with regard to recently infected patients presenting at infusion centers, whether patients are more likely to continue testing positive, and when patients are cleared to come back. Dr. Ruderman said his center has a 20-day rule for returning after having COVID-19, while Dr. Cush said his center allows patients to come in if they test negative after 7-10 days.

“One of the things we’re struggling with is our infusion center, and one of the questions that keeps coming up is when can people come back after a COVID infection?” he said. “If you’re on a drug at home, that’s up to you and the patient. But in the infusion [center], then you have other people sitting around there.”

Dr. Kavanaugh said there is no current data for how long patients with rheumatic disease shed virus, or how long a positive test can be measured. “You definitely will continue to shed, and you’ll be detectable for a while,” he said.

Dr. Cush and Dr. Kavanaugh reported having financial relationships with numerous pharmaceutical companies.

The COVID-19 pandemic led to a decrease in the proportion of patients with rheumatic diseases who stopped taking their disease-modifying antirheumatic drugs (DMARDs), but the percentage who interrupted DMARD treatment increased later in the pandemic, according to speakers at the 2022 Rheumatology Winter Clinical Symposium.

“People seem to be less anxious, but they’re interrupting their DMARD therapy more, more recently than in the pits of COVID, if you will,” said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, and director of RWCS.

RWCS 2022 screenshot

Dr. Kavanaugh and his copresenter Jack Cush, MD, were discussing the results of a recent study published in Arthritis Care & Research that evaluated 2,424 patients with rheumatic diseases who completed a baseline and at least one follow-up survey issued by patient organizations between March 2020 and May 2021, with a median of five follow-up surveys completed. The patients included in the study were aged a mean of 57 years, 86.6% were women, 90.5% were White, 41.8% had rheumatoid arthritis (RA), 14.8% had antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and 12.4% had psoriatic arthritis. Overall, 52.6% were on biologics or a Janus kinase (JAK) inhibitor, 30.0% were receiving methotrexate, 21.4% were taking hydroxychloroquine, and 28.6% were receiving low-dose (24.0%) or high-dose (4.6%) glucocorticoids.

Patients’ T-scores on the anxiety short form Patient-Reported Outcomes Measurement Information System (PROMIS) survey significantly decreased from a score of 58.7 in April 2020 to a score of 53.7 in May 2021 (P < .001), but there was a significant decrease in the interruption of DMARD treatment between April and December 2020 (11.2% vs. 7.5%; P < .001). This percentage rose significantly to 14.0% by May 2021 (P < .001). Patients who stopped using DMARDs were significantly associated with predicted incidence of severe flare in the next survey in adjusted models (12.9% vs. 8.0%; odds ratio, 1.71; 95% confidence interval, 1.23-2.36).

The results tell us “that we as a discipline are not doing a good job educating our patients,” said Dr. Cush, a rheumatologist based in Dallas, Tex., and executive editor of RheumNow.com.

“I wish we – and I’m really talking about myself – but myself and my practice were more proactive when COVID happened [in] sending out regular bulletins: ‘Don’t stop your therapy; these are the things you get; get the test that you need to get done,’ ” he said. “We let a lot of things go on autopilot with the patient driving throughout COVID. Even now, it’s happening. And this is a problem, and there are going to be consequences to this.”

Dr. Kavanaugh agreed with Dr. Cush’s assessment, suggesting that the pandemic came up quickly enough that it was difficult to be proactive with the situation.
 

Patients on JAK inhibitors as new COVID-19 risk group?

Another standout study on COVID-19 from 2021 was an analysis of the COVID-19 Global Rheumatology Alliance physician registry that examined risk of COVID-19 severity for patients with RA taking biologic or targeted synthetic DMARDs (tsDMARDs), which was presented at the 2021 EULAR congress and later published in Annals of the Rheumatic Diseases.

The researchers evaluated 2,869 patients March 2020 and April 2021 who were receiving abatacept (237 patients), rituximab (364 patients), interleukin (IL)-6 inhibitors (317 patients), JAK inhibitors (563 patients), or tumor necrosis factor (TNF) inhibitors such as infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab (1,388 patients) before developing COVID-19. Data about biologics or tsDMARDs were collected as a drug class. Patients in the study were mostly White (69.0%) women (80.8%) with a mean age of 56.7 years who lived in Europe (51.8%) or North America (35.0%). The researchers examined the severity of COVID-19 among all patients studied and calculated odds ratios based on drug class, with the TNF inhibitor group serving as a reference.

“[I]n this case, they said that the baseline use of rituximab was associated with more severity, and you see the severity being hospitalization and ICU and deaths. They found a signal for the JAK inhibitors that is not found in the other studies,” Dr. Kavanaugh said.

Overall, they found 21% of patients in the registry were hospitalized and 5.5% died, with rituximab (OR, 4.15; 95% CI, 3.16-5.44) and JAK inhibitors (OR, 2.06; 95% CI, 1.60-2.65) associated with more severe COVID-19 outcomes. Specifically, rituximab was associated with greater likelihood of hospitalization (OR, 4.53; 95% CI, 3.32-6.18), hospitalization with oxygen/ventilation (OR, 2.87; 95% CI, 2.03-4.06), need for mechanical ventilation (OR, 4.05; 95% CI, 3.08-5.33), and mortality (OR, 4.57; 95% CI, 3.32-9.01), compared with TNF inhibitors. For JAK inhibitors, there was also a greater likelihood of hospitalization (OR, 2.40; 95% CI, 1.78-3.24), hospitalization with oxygen/ventilation (OR, 1.55; 95% CI, 1.04-2.18), need for mechanical ventilation (OR, 2.03; 95% CI, 1.56-2.62), and mortality (OR, 2.04; 95% CI, 1.58-2.65), compared with the TNF inhibitors group. Associations between COVID-19 severity and abatacept or IL-6 inhibitors were not identified.

Commenting on the study in a question-and-answer session, Roy Fleischmann, MD, said the part of the study that identified a signal for JAK inhibitors was “very interesting.” He called attention to a rapid response comment to the study, which questioned if it was the drug class itself that caused the risk for severe disease. “This is very important, because actually, the patients who stop the JAK [inhibitor], that’s what drove the illness. The patients [who] continued the JAK [inhibitor], very few of them had illness,” said Dr. Fleischmann, clinical professor of medicine at the University of Texas Southwestern Medical School and codirector of the Metroplex Clinical Research Center, both in Dallas, Tex.
 

Confusion among patients during COVID-19

Alvin Wells, MD, PhD, asked the copresenters during the Q&A session whether they had any clinical pearls for the audience on how they manage treatment of patients with rheumatic disease with potential COVID-19 risk. “I think the confusion with our patients and COVID is what the ACR has put out with their guidelines,” said Dr. Wells, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc.

Dr. Cush said he has three rules he follows: lower and discontinue steroids, avoid rituximab as a starting treatment and negotiate if patients are already taking it, and don’t stop any therapy.

“I want disease control. I think being under control is what keeps you away from risk of COVID and hospitalization,” Dr. Cush said. “I think being uncontrolled and inflamed, whether it’s our [patients with] inflammatory arthritis or lupus or, worse, vasculitis [or] myositis, those are the ones at high risk of progression from being just infected to being sick and in the hospital.”

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, posed the question of getting somewhat back to normal during COVID-19 with regard to recently infected patients presenting at infusion centers, whether patients are more likely to continue testing positive, and when patients are cleared to come back. Dr. Ruderman said his center has a 20-day rule for returning after having COVID-19, while Dr. Cush said his center allows patients to come in if they test negative after 7-10 days.

“One of the things we’re struggling with is our infusion center, and one of the questions that keeps coming up is when can people come back after a COVID infection?” he said. “If you’re on a drug at home, that’s up to you and the patient. But in the infusion [center], then you have other people sitting around there.”

Dr. Kavanaugh said there is no current data for how long patients with rheumatic disease shed virus, or how long a positive test can be measured. “You definitely will continue to shed, and you’ll be detectable for a while,” he said.

Dr. Cush and Dr. Kavanaugh reported having financial relationships with numerous pharmaceutical companies.

Current selection criteria for autologous hematopoietic stem cell transplant (AHSCT) in patients with rapidly progressing systemic sclerosis were validated in a study presented at the annual meeting of the Canadian Rheumatology Association.

The study, which associated AHSCT with improvement in overall survival and an acceptable risk of adverse events, “provides valuable real-world, long-term data pertaining to key clinical outcomes to support the use of AHSCT in patients with rapidly progressing systemic sclerosis,” reported Nancy Maltez, MD, a rheumatologist and clinical investigator who is on the faculty of the University of Ottawa.

Fnaq / Wikimedia Commons / CC BY-SA 4.0

The prospective study enrolled 85 patients in Canada and 41 patients in France with rapidly progressing systemic sclerosis. The patients in both countries were enrolled with the same eligibility criteria for AHSCT, but patients in France underwent AHSCT while the patients in Canada were treated with conventional therapies, such as cyclophosphamide.

On the primary outcome of overall survival, the Kaplan-Meier curve split almost immediately in favor of AHSCT. At 4 years, more than 25% of patients in the conventional therapy group had died versus less than 5% of those who underwent AHSCT. Although the mortality curve did slope downwards in the AHSCT group over the subsequent 6 years of follow-up, it largely paralleled and remained superior to convention therapy.
 

About 50% survival advantage seen for AHSCT

In this nonrandomized study, the statistical survival advantage of AHSCT was not provided, but the survival graph showed about 75% survival at 8 years of follow-up in the AHSCT group, compared with about 50% survival in the conventional-therapy group.

Many of the secondary outcomes, including those evaluating skin involvement, preservation of lung function, and absence of renal complications also favored AHSCT, according to Dr. Maltez.

On the modified Rodnan skin score, a significant difference (P < .001) observed at 12 months was sustained at 36 months, when the score was 4.48 points lower among patients treated with AHSCT. The difference in forced vital capacity (FVC) was about 10% higher (P < .0001) in the AHSCT group.

Over long-term follow-up, the incidence of scleroderma renal crisis per 100 person-years was 6.02 cases in the conventional therapy group versus 0.58 cases (P < .001) in the AHSCT group. There was no significant difference in the proportion of patients in the two groups receiving a pacemaker over the course of follow-up, but the rate of new malignancies per 100 person-years was 3.71 in the conventional care group versus 0.58 (P < .001) in the AHSCT group.

Significant complications attributed to AHSCT were uncommon. This is important, because AHSCT was not uniformly well tolerated in the initial trials. The first of three randomized trials with AHSCT in progressive systemic sclerosis was published more than 10 years ago after a series of promising early phase trials. Each associated AHSCT with benefit, but patient selection appeared to be important.

In the ASSIST trial of 2011, AHSCT was associated with significant reductions in skin involvement and improvements in pulmonary function relative to cyclophosphamide, but enrollment was stopped after only 19 patients, and follow-up extended to only 2 years.

Substantial AHSCT-related mortality in ASTIS

In the second trial, called ASTIS, AHSCT was associated with a higher rate of mortality than cyclophosphamide after 1 year of follow-up, although there was a significantly greater long-term event-free survival for AHSCT when patients were followed out to 4 years. This study reinforced the need for cardiac screening because of because of concern that severe cardiac compromise contributed to the increased risk of AHSCT-related mortality.

The SCOT trial employed a high-intensity myeloablative conditioning regimen and total body irradiation prior to AHSCT. It is not clear that these contributed to improved survival, particularly because of the risk for irradiation to exacerbate complications in the lung and kidney, but AHSCT-related mortality was only 3% at 54 months. Patient enrollment criteria in this trial were also suspected of having played a role in the favorable results.

In the Canadian-French collaborative study, patients were considered eligible for AHSCT if they met the enrollment criteria used in the ASTIS trial, according to Dr. Maltez. She attributed the low rates of early mortality and relative absence of transplant-related death to the lessons learned in the published trials.

Overall, the data support the routine but selective use of AHSCT in rapidly progressing systemic sclerosis, Dr. Maltez concluded.

Maria Carolina Oliveira, MD, of the department of internal medicine at the University of São Paulo, generally agreed. A coauthor of a recent review of AHSCT for systemic sclerosis, Dr. Oliveira emphasized that patient selection is critical.

“AHSCT for systemic sclerosis has very specific inclusion criteria. Indeed, it is indicated for patients with severe and progressive disease but under two specific conditions: severe and progressive diffuse skin involvement and/or progressive interstitial lung disease,” she said in an interview.

Because of the thin line between benefit and risk according to disease subtypes and comorbidities, she said that it is important to be aware of relative contraindications and to recognize the risks of AHSCT.

At this time, and in the absence of better biomarkers to identify those most likely to benefit, “patients with other forms of severe scleroderma, such as those with pulmonary hypertension, scleroderma renal crisis, or severe cardiac involvement, for example, are not eligible,” she said.

Dr. Maltez and Dr. Oliveira reported having no potential conflicts of interest.

Current selection criteria for autologous hematopoietic stem cell transplant (AHSCT) in patients with rapidly progressing systemic sclerosis were validated in a study presented at the annual meeting of the Canadian Rheumatology Association.

The study, which associated AHSCT with improvement in overall survival and an acceptable risk of adverse events, “provides valuable real-world, long-term data pertaining to key clinical outcomes to support the use of AHSCT in patients with rapidly progressing systemic sclerosis,” reported Nancy Maltez, MD, a rheumatologist and clinical investigator who is on the faculty of the University of Ottawa.

Fnaq / Wikimedia Commons / CC BY-SA 4.0

The prospective study enrolled 85 patients in Canada and 41 patients in France with rapidly progressing systemic sclerosis. The patients in both countries were enrolled with the same eligibility criteria for AHSCT, but patients in France underwent AHSCT while the patients in Canada were treated with conventional therapies, such as cyclophosphamide.

On the primary outcome of overall survival, the Kaplan-Meier curve split almost immediately in favor of AHSCT. At 4 years, more than 25% of patients in the conventional therapy group had died versus less than 5% of those who underwent AHSCT. Although the mortality curve did slope downwards in the AHSCT group over the subsequent 6 years of follow-up, it largely paralleled and remained superior to convention therapy.
 

About 50% survival advantage seen for AHSCT

In this nonrandomized study, the statistical survival advantage of AHSCT was not provided, but the survival graph showed about 75% survival at 8 years of follow-up in the AHSCT group, compared with about 50% survival in the conventional-therapy group.

Many of the secondary outcomes, including those evaluating skin involvement, preservation of lung function, and absence of renal complications also favored AHSCT, according to Dr. Maltez.

On the modified Rodnan skin score, a significant difference (P < .001) observed at 12 months was sustained at 36 months, when the score was 4.48 points lower among patients treated with AHSCT. The difference in forced vital capacity (FVC) was about 10% higher (P < .0001) in the AHSCT group.

Over long-term follow-up, the incidence of scleroderma renal crisis per 100 person-years was 6.02 cases in the conventional therapy group versus 0.58 cases (P < .001) in the AHSCT group. There was no significant difference in the proportion of patients in the two groups receiving a pacemaker over the course of follow-up, but the rate of new malignancies per 100 person-years was 3.71 in the conventional care group versus 0.58 (P < .001) in the AHSCT group.

Significant complications attributed to AHSCT were uncommon. This is important, because AHSCT was not uniformly well tolerated in the initial trials. The first of three randomized trials with AHSCT in progressive systemic sclerosis was published more than 10 years ago after a series of promising early phase trials. Each associated AHSCT with benefit, but patient selection appeared to be important.

In the ASSIST trial of 2011, AHSCT was associated with significant reductions in skin involvement and improvements in pulmonary function relative to cyclophosphamide, but enrollment was stopped after only 19 patients, and follow-up extended to only 2 years.

Substantial AHSCT-related mortality in ASTIS

In the second trial, called ASTIS, AHSCT was associated with a higher rate of mortality than cyclophosphamide after 1 year of follow-up, although there was a significantly greater long-term event-free survival for AHSCT when patients were followed out to 4 years. This study reinforced the need for cardiac screening because of because of concern that severe cardiac compromise contributed to the increased risk of AHSCT-related mortality.

The SCOT trial employed a high-intensity myeloablative conditioning regimen and total body irradiation prior to AHSCT. It is not clear that these contributed to improved survival, particularly because of the risk for irradiation to exacerbate complications in the lung and kidney, but AHSCT-related mortality was only 3% at 54 months. Patient enrollment criteria in this trial were also suspected of having played a role in the favorable results.

In the Canadian-French collaborative study, patients were considered eligible for AHSCT if they met the enrollment criteria used in the ASTIS trial, according to Dr. Maltez. She attributed the low rates of early mortality and relative absence of transplant-related death to the lessons learned in the published trials.

Overall, the data support the routine but selective use of AHSCT in rapidly progressing systemic sclerosis, Dr. Maltez concluded.

Maria Carolina Oliveira, MD, of the department of internal medicine at the University of São Paulo, generally agreed. A coauthor of a recent review of AHSCT for systemic sclerosis, Dr. Oliveira emphasized that patient selection is critical.

“AHSCT for systemic sclerosis has very specific inclusion criteria. Indeed, it is indicated for patients with severe and progressive disease but under two specific conditions: severe and progressive diffuse skin involvement and/or progressive interstitial lung disease,” she said in an interview.

Because of the thin line between benefit and risk according to disease subtypes and comorbidities, she said that it is important to be aware of relative contraindications and to recognize the risks of AHSCT.

At this time, and in the absence of better biomarkers to identify those most likely to benefit, “patients with other forms of severe scleroderma, such as those with pulmonary hypertension, scleroderma renal crisis, or severe cardiac involvement, for example, are not eligible,” she said.

Dr. Maltez and Dr. Oliveira reported having no potential conflicts of interest.

Current selection criteria for autologous hematopoietic stem cell transplant (AHSCT) in patients with rapidly progressing systemic sclerosis were validated in a study presented at the annual meeting of the Canadian Rheumatology Association.

The study, which associated AHSCT with improvement in overall survival and an acceptable risk of adverse events, “provides valuable real-world, long-term data pertaining to key clinical outcomes to support the use of AHSCT in patients with rapidly progressing systemic sclerosis,” reported Nancy Maltez, MD, a rheumatologist and clinical investigator who is on the faculty of the University of Ottawa.

Fnaq / Wikimedia Commons / CC BY-SA 4.0

The prospective study enrolled 85 patients in Canada and 41 patients in France with rapidly progressing systemic sclerosis. The patients in both countries were enrolled with the same eligibility criteria for AHSCT, but patients in France underwent AHSCT while the patients in Canada were treated with conventional therapies, such as cyclophosphamide.

On the primary outcome of overall survival, the Kaplan-Meier curve split almost immediately in favor of AHSCT. At 4 years, more than 25% of patients in the conventional therapy group had died versus less than 5% of those who underwent AHSCT. Although the mortality curve did slope downwards in the AHSCT group over the subsequent 6 years of follow-up, it largely paralleled and remained superior to convention therapy.
 

About 50% survival advantage seen for AHSCT

In this nonrandomized study, the statistical survival advantage of AHSCT was not provided, but the survival graph showed about 75% survival at 8 years of follow-up in the AHSCT group, compared with about 50% survival in the conventional-therapy group.

Many of the secondary outcomes, including those evaluating skin involvement, preservation of lung function, and absence of renal complications also favored AHSCT, according to Dr. Maltez.

On the modified Rodnan skin score, a significant difference (P < .001) observed at 12 months was sustained at 36 months, when the score was 4.48 points lower among patients treated with AHSCT. The difference in forced vital capacity (FVC) was about 10% higher (P < .0001) in the AHSCT group.

Over long-term follow-up, the incidence of scleroderma renal crisis per 100 person-years was 6.02 cases in the conventional therapy group versus 0.58 cases (P < .001) in the AHSCT group. There was no significant difference in the proportion of patients in the two groups receiving a pacemaker over the course of follow-up, but the rate of new malignancies per 100 person-years was 3.71 in the conventional care group versus 0.58 (P < .001) in the AHSCT group.

Significant complications attributed to AHSCT were uncommon. This is important, because AHSCT was not uniformly well tolerated in the initial trials. The first of three randomized trials with AHSCT in progressive systemic sclerosis was published more than 10 years ago after a series of promising early phase trials. Each associated AHSCT with benefit, but patient selection appeared to be important.

In the ASSIST trial of 2011, AHSCT was associated with significant reductions in skin involvement and improvements in pulmonary function relative to cyclophosphamide, but enrollment was stopped after only 19 patients, and follow-up extended to only 2 years.

Substantial AHSCT-related mortality in ASTIS

In the second trial, called ASTIS, AHSCT was associated with a higher rate of mortality than cyclophosphamide after 1 year of follow-up, although there was a significantly greater long-term event-free survival for AHSCT when patients were followed out to 4 years. This study reinforced the need for cardiac screening because of because of concern that severe cardiac compromise contributed to the increased risk of AHSCT-related mortality.

The SCOT trial employed a high-intensity myeloablative conditioning regimen and total body irradiation prior to AHSCT. It is not clear that these contributed to improved survival, particularly because of the risk for irradiation to exacerbate complications in the lung and kidney, but AHSCT-related mortality was only 3% at 54 months. Patient enrollment criteria in this trial were also suspected of having played a role in the favorable results.

In the Canadian-French collaborative study, patients were considered eligible for AHSCT if they met the enrollment criteria used in the ASTIS trial, according to Dr. Maltez. She attributed the low rates of early mortality and relative absence of transplant-related death to the lessons learned in the published trials.

Overall, the data support the routine but selective use of AHSCT in rapidly progressing systemic sclerosis, Dr. Maltez concluded.

Maria Carolina Oliveira, MD, of the department of internal medicine at the University of São Paulo, generally agreed. A coauthor of a recent review of AHSCT for systemic sclerosis, Dr. Oliveira emphasized that patient selection is critical.

“AHSCT for systemic sclerosis has very specific inclusion criteria. Indeed, it is indicated for patients with severe and progressive disease but under two specific conditions: severe and progressive diffuse skin involvement and/or progressive interstitial lung disease,” she said in an interview.

Because of the thin line between benefit and risk according to disease subtypes and comorbidities, she said that it is important to be aware of relative contraindications and to recognize the risks of AHSCT.

At this time, and in the absence of better biomarkers to identify those most likely to benefit, “patients with other forms of severe scleroderma, such as those with pulmonary hypertension, scleroderma renal crisis, or severe cardiac involvement, for example, are not eligible,” she said.

Dr. Maltez and Dr. Oliveira reported having no potential conflicts of interest.