Lupus & Connective Tissue Diseases

An alternative disease activity index for patients with systemic lupus erythematosus called the SLE-DAS (Disease Activity Score) has shown similar results to the Lupus Low Disease Activity State (LLDAS) in classifying low disease activity but may be easier to potentially apply in daily clinical practice in treat-to-target strategies, according to research presented at the annual European Congress of Rheumatology, held online this year because of COVID-19.

A treat-to-target approach, in which therapies are adjusted and the patient monitored to achieve the desired endpoint, has been proposed for patients with SLE. Clinical remission is the ideal goal, followed by achieving low disease activity (LDA) when clinical remission is unattainable, the first author of the SLE-DAS study, Helena Assunção, MD, of the department of rheumatology at Centro Hospitalar e Universitário de Coimbra (Portugal), said in an interview prior to the presentation of the study at the e-congress.

But to conduct a treat-to-target approach in the clinical setting, clinicians must have reliable, user-friendly targets to assess a patient’s progress, she said. But that’s not available right now. Proposed definitions of LDA, such as the LLDAS, are based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). This index doesn’t address some important manifestations of SLE and it is scored dichotomously – for example, giving a similar score for thrombocytopenia when platelet count is reduced to 100,000 or to 10,000.

To compensate for these limitations, the current LLDAS definition also requires the Physician Global Assessment and other steps, including a review of medication and changes to treatment or clinical status since the previous visit.

“It is not easy to apply,” Dr. Assunção said.

The SLE-DAS is a continuous index involving 17 parameters (4 continuous: arthritis, proteinuria, thrombocytopenia, and leukopenia), assigning higher scores when a manifestation is more severe, and has manifestation information that SLEDAI-2K lacks (cardiopulmonary involvement, lupus enteritis, and hemolytic anemia).

In contrast, the LLDAS is defined as:
 

• A SLEDAI-2k score of 4 or less with no major organ involvement
• No new disease activity
• A physician global assessment of the patient of 1 or less on a 0-3 scale
• Maintenance on a prednisolone dosage of 7.5 mg/day or less
• Maintenance on a standard immunosuppressive regimen

A previous study validated the SLE-DAS (Ann Rheum Dis. 2019 Mar;78[3]:365-71), and another exploratory study identified a cutoff SLE-DAS value of 3.77 or lower for LDA with SLE-DAS (Ann Rheum Dis. 2019;78:411-2).

Her group compared LDA status as measured with LLDAS versus the SLE-DAS in a cross-sectional study of 292 consecutive patients at their hospital. LDA on the SLE-DAS was defined as a score 3.77 or lower and a prednisolone dose of 7.5 mg/day or less. A total of 85% of patients were in LDA with SLE-DAS and 83.9% with LLDAS, and the agreement between LLDAS and SLE-DAS LDA was very high (Cohen’s kappa coefficient test; kappa = 0.831; P < .01). Out of 292 patients, only 13 were classified differently by the two definitions, 8 of which were classified as LDA by SLE-DAS, and 5 by LLDAS. Overall, 87% of patients were women and had a mean age of nearly 49 years, with a mean disease duration of about 14 years.

Dr. Assunção feels that the SLE-DAS LDA should be sufficient to monitor disease activity without adding the Physician Global Assessment and other steps, which would make it easier to apply than LLDAS. The fact that it is based on a continuous index is also an important difference. “Especially for low disease activity, it’s very good to be able to define it with a continuous index, because you are not that bad, but not that good, you’re in the middle,” she said.

The study should be regarded as exploratory, she said, but the results were encouraging. “We got similar results, and it’s definitely easier to apply.” She can also personally attest that the new model is easier to use, since she personally collected data for LLDAS assignment. “I had to check this, and this, and this … [SLE-DAS] is easier.”

Future work from her group will aim at deriving and validating a more robust definition of LDA, which will again be compared with the current LLDAS definition.

Her colleagues have already developed and validated a definition for clinical remission using SLE-DAS, although those results have not yet been published. They hope to define activity states using SLE-DAS, including mild, moderate, and high disease activity.

The team has produced an online SLE-DAS calculator (http://sle-das.eu/) where clinicians can score the 17 parameters. “You just input the values and it gives a number reflecting disease activity. Using this definition of SLE-DAS LDA you only need that number and to verify that the prednisolone dose is equal to or inferior to 7.5 mg/day,” said Dr. Assunção.

The study received no funding. Dr. Assunção has no financial disclosures, but one coauthor reported receiving grant/research support from Pfizer and AbbVie and serving as a consultant to Pfizer, AbbVie, Roche, Lilly, and Novartis.

SOURCE: Assunção H et al. Ann Rheum Dis 2020;79[suppl 1]:60, Abstract OP0092.

An alternative disease activity index for patients with systemic lupus erythematosus called the SLE-DAS (Disease Activity Score) has shown similar results to the Lupus Low Disease Activity State (LLDAS) in classifying low disease activity but may be easier to potentially apply in daily clinical practice in treat-to-target strategies, according to research presented at the annual European Congress of Rheumatology, held online this year because of COVID-19.

A treat-to-target approach, in which therapies are adjusted and the patient monitored to achieve the desired endpoint, has been proposed for patients with SLE. Clinical remission is the ideal goal, followed by achieving low disease activity (LDA) when clinical remission is unattainable, the first author of the SLE-DAS study, Helena Assunção, MD, of the department of rheumatology at Centro Hospitalar e Universitário de Coimbra (Portugal), said in an interview prior to the presentation of the study at the e-congress.

But to conduct a treat-to-target approach in the clinical setting, clinicians must have reliable, user-friendly targets to assess a patient’s progress, she said. But that’s not available right now. Proposed definitions of LDA, such as the LLDAS, are based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). This index doesn’t address some important manifestations of SLE and it is scored dichotomously – for example, giving a similar score for thrombocytopenia when platelet count is reduced to 100,000 or to 10,000.

To compensate for these limitations, the current LLDAS definition also requires the Physician Global Assessment and other steps, including a review of medication and changes to treatment or clinical status since the previous visit.

“It is not easy to apply,” Dr. Assunção said.

The SLE-DAS is a continuous index involving 17 parameters (4 continuous: arthritis, proteinuria, thrombocytopenia, and leukopenia), assigning higher scores when a manifestation is more severe, and has manifestation information that SLEDAI-2K lacks (cardiopulmonary involvement, lupus enteritis, and hemolytic anemia).

In contrast, the LLDAS is defined as:
 

• A SLEDAI-2k score of 4 or less with no major organ involvement
• No new disease activity
• A physician global assessment of the patient of 1 or less on a 0-3 scale
• Maintenance on a prednisolone dosage of 7.5 mg/day or less
• Maintenance on a standard immunosuppressive regimen

A previous study validated the SLE-DAS (Ann Rheum Dis. 2019 Mar;78[3]:365-71), and another exploratory study identified a cutoff SLE-DAS value of 3.77 or lower for LDA with SLE-DAS (Ann Rheum Dis. 2019;78:411-2).

Her group compared LDA status as measured with LLDAS versus the SLE-DAS in a cross-sectional study of 292 consecutive patients at their hospital. LDA on the SLE-DAS was defined as a score 3.77 or lower and a prednisolone dose of 7.5 mg/day or less. A total of 85% of patients were in LDA with SLE-DAS and 83.9% with LLDAS, and the agreement between LLDAS and SLE-DAS LDA was very high (Cohen’s kappa coefficient test; kappa = 0.831; P < .01). Out of 292 patients, only 13 were classified differently by the two definitions, 8 of which were classified as LDA by SLE-DAS, and 5 by LLDAS. Overall, 87% of patients were women and had a mean age of nearly 49 years, with a mean disease duration of about 14 years.

Dr. Assunção feels that the SLE-DAS LDA should be sufficient to monitor disease activity without adding the Physician Global Assessment and other steps, which would make it easier to apply than LLDAS. The fact that it is based on a continuous index is also an important difference. “Especially for low disease activity, it’s very good to be able to define it with a continuous index, because you are not that bad, but not that good, you’re in the middle,” she said.

The study should be regarded as exploratory, she said, but the results were encouraging. “We got similar results, and it’s definitely easier to apply.” She can also personally attest that the new model is easier to use, since she personally collected data for LLDAS assignment. “I had to check this, and this, and this … [SLE-DAS] is easier.”

Future work from her group will aim at deriving and validating a more robust definition of LDA, which will again be compared with the current LLDAS definition.

Her colleagues have already developed and validated a definition for clinical remission using SLE-DAS, although those results have not yet been published. They hope to define activity states using SLE-DAS, including mild, moderate, and high disease activity.

The team has produced an online SLE-DAS calculator (http://sle-das.eu/) where clinicians can score the 17 parameters. “You just input the values and it gives a number reflecting disease activity. Using this definition of SLE-DAS LDA you only need that number and to verify that the prednisolone dose is equal to or inferior to 7.5 mg/day,” said Dr. Assunção.

The study received no funding. Dr. Assunção has no financial disclosures, but one coauthor reported receiving grant/research support from Pfizer and AbbVie and serving as a consultant to Pfizer, AbbVie, Roche, Lilly, and Novartis.

SOURCE: Assunção H et al. Ann Rheum Dis 2020;79[suppl 1]:60, Abstract OP0092.

An alternative disease activity index for patients with systemic lupus erythematosus called the SLE-DAS (Disease Activity Score) has shown similar results to the Lupus Low Disease Activity State (LLDAS) in classifying low disease activity but may be easier to potentially apply in daily clinical practice in treat-to-target strategies, according to research presented at the annual European Congress of Rheumatology, held online this year because of COVID-19.

A treat-to-target approach, in which therapies are adjusted and the patient monitored to achieve the desired endpoint, has been proposed for patients with SLE. Clinical remission is the ideal goal, followed by achieving low disease activity (LDA) when clinical remission is unattainable, the first author of the SLE-DAS study, Helena Assunção, MD, of the department of rheumatology at Centro Hospitalar e Universitário de Coimbra (Portugal), said in an interview prior to the presentation of the study at the e-congress.

But to conduct a treat-to-target approach in the clinical setting, clinicians must have reliable, user-friendly targets to assess a patient’s progress, she said. But that’s not available right now. Proposed definitions of LDA, such as the LLDAS, are based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). This index doesn’t address some important manifestations of SLE and it is scored dichotomously – for example, giving a similar score for thrombocytopenia when platelet count is reduced to 100,000 or to 10,000.

To compensate for these limitations, the current LLDAS definition also requires the Physician Global Assessment and other steps, including a review of medication and changes to treatment or clinical status since the previous visit.

“It is not easy to apply,” Dr. Assunção said.

The SLE-DAS is a continuous index involving 17 parameters (4 continuous: arthritis, proteinuria, thrombocytopenia, and leukopenia), assigning higher scores when a manifestation is more severe, and has manifestation information that SLEDAI-2K lacks (cardiopulmonary involvement, lupus enteritis, and hemolytic anemia).

In contrast, the LLDAS is defined as:
 

• A SLEDAI-2k score of 4 or less with no major organ involvement
• No new disease activity
• A physician global assessment of the patient of 1 or less on a 0-3 scale
• Maintenance on a prednisolone dosage of 7.5 mg/day or less
• Maintenance on a standard immunosuppressive regimen

A previous study validated the SLE-DAS (Ann Rheum Dis. 2019 Mar;78[3]:365-71), and another exploratory study identified a cutoff SLE-DAS value of 3.77 or lower for LDA with SLE-DAS (Ann Rheum Dis. 2019;78:411-2).

Her group compared LDA status as measured with LLDAS versus the SLE-DAS in a cross-sectional study of 292 consecutive patients at their hospital. LDA on the SLE-DAS was defined as a score 3.77 or lower and a prednisolone dose of 7.5 mg/day or less. A total of 85% of patients were in LDA with SLE-DAS and 83.9% with LLDAS, and the agreement between LLDAS and SLE-DAS LDA was very high (Cohen’s kappa coefficient test; kappa = 0.831; P < .01). Out of 292 patients, only 13 were classified differently by the two definitions, 8 of which were classified as LDA by SLE-DAS, and 5 by LLDAS. Overall, 87% of patients were women and had a mean age of nearly 49 years, with a mean disease duration of about 14 years.

Dr. Assunção feels that the SLE-DAS LDA should be sufficient to monitor disease activity without adding the Physician Global Assessment and other steps, which would make it easier to apply than LLDAS. The fact that it is based on a continuous index is also an important difference. “Especially for low disease activity, it’s very good to be able to define it with a continuous index, because you are not that bad, but not that good, you’re in the middle,” she said.

The study should be regarded as exploratory, she said, but the results were encouraging. “We got similar results, and it’s definitely easier to apply.” She can also personally attest that the new model is easier to use, since she personally collected data for LLDAS assignment. “I had to check this, and this, and this … [SLE-DAS] is easier.”

Future work from her group will aim at deriving and validating a more robust definition of LDA, which will again be compared with the current LLDAS definition.

Her colleagues have already developed and validated a definition for clinical remission using SLE-DAS, although those results have not yet been published. They hope to define activity states using SLE-DAS, including mild, moderate, and high disease activity.

The team has produced an online SLE-DAS calculator (http://sle-das.eu/) where clinicians can score the 17 parameters. “You just input the values and it gives a number reflecting disease activity. Using this definition of SLE-DAS LDA you only need that number and to verify that the prednisolone dose is equal to or inferior to 7.5 mg/day,” said Dr. Assunção.

The study received no funding. Dr. Assunção has no financial disclosures, but one coauthor reported receiving grant/research support from Pfizer and AbbVie and serving as a consultant to Pfizer, AbbVie, Roche, Lilly, and Novartis.

SOURCE: Assunção H et al. Ann Rheum Dis 2020;79[suppl 1]:60, Abstract OP0092.

Patients on a tumor necrosis factor inhibitor for their rheumatic disease when they became infected with COVID-19 were markedly less likely to subsequently require hospitalization, according to intriguing early evidence from the COVID-19 Global Rheumatology Alliance Registry.

On the other hand, those registry patients who were on 10 mg of prednisone or more daily when they got infected were more than twice as likely to be hospitalized than were those who were not on corticosteroids, even after controlling for the severity of their rheumatic disease and other potential confounders, Jinoos Yazdany, MD, reported at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

“We saw a signal with moderate to high-dose steroids. I think it’s something we’re going to have to keep an eye out on as more data come in,” said Dr. Yazdany, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital.

The global registry launched on March 24, 2020, and was quickly embraced by rheumatologists from around the world. By May 12, the registry included more than 1,300 patients with a range of rheumatic diseases, all with confirmed COVID-19 infection as a requisite for enrollment; the cases were submitted by more than 300 rheumatologists in 40 countries. The registry is supported by the ACR and European League Against Rheumatism.

Dr. Yazdany, a member of the registry steering committee, described the project’s two main goals: To learn the outcomes of COVID-19–infected patients with various rheumatic diseases and to make inferences regarding the impact of the immunosuppressive and antimalarial medications widely prescribed by rheumatologists.

She presented soon-to-be-published data on the characteristics and disposition of the first 600 patients, 46% of whom were hospitalized and 9% died. A caveat regarding the registry, she noted, is that these are observational data and thus potentially subject to unrecognized confounders. Also, the registry population is skewed toward the sicker end of the COVID-19 disease spectrum because while all participants have confirmed infection, testing for the infection has been notoriously uneven. Many people are infected asymptomatically and thus may not undergo testing even where readily available.
 

Early key findings from registry

The risk factors for more severe infection resulting in hospitalization in patients with rheumatic diseases are by and large the same drivers described in the general population: older age and comorbid conditions including diabetes, hypertension, cardiovascular disease, obesity, chronic kidney disease, and lung disease. Notably, however, patients on the equivalent of 10 mg/day of prednisone or more were at a 105% increased risk for hospitalization, compared with those not on corticosteroids after adjustment for age, comorbid conditions, and rheumatic disease severity.

Patients on a background tumor necrosis factor (TNF) inhibitor had an adjusted 60% reduction in risk of hospitalization. This apparent protective effect against more severe COVID-19 disease is mechanistically plausible: In animal studies, being on a TNF inhibitor has been associated with less severe infection following exposure to influenza virus, Dr. Yazdany observed.

COVID-infected patients on any biologic disease-modifying antirheumatic drug had a 54% decreased risk of hospitalization. However, in this early analysis, the study was sufficiently powered only to specifically assess the impact of TNF inhibitors, since those agents were by far the most commonly used biologics. As the registry grows, it will be possible to analyze the impact of other antirheumatic medications.

Being on hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization.

The only rheumatic disease diagnosis with an odds of hospitalization significantly different from that of RA patients was systemic lupus erythematosus (SLE). Lupus patients were at 80% increased risk of hospitalization. Although this was a statistically significant difference, Dr. Yazdany cautioned against making too much of it because of the strong potential for unmeasured confounding. In particular, lupus patients as a group are known to rate on the lower end of measures of social determinants of health, a status that is an established major risk factor for COVID-19 disease.

“A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” she said.

Being on background NSAIDs at the time of SARS-CoV-2 infection was not associated with increased risk of hospitalization; in fact, NSAID users were 36% less likely to be hospitalized for their COVID-19 disease, although this difference didn’t reach statistical significance.

Dr. Yazdany urged her fellow rheumatologists to enter their cases on the registry website: rheum-covid.org. There they can also join the registry mailing list and receive weekly updates.
 

Other recent insights on COVID-19 in rheumatology

An as-yet unpublished U.K. observational study involving electronic health record data on 17 million people included 885,000 individuals with RA, SLE, or psoriasis. After extensive statistical controlling for the known risk factors for severe COVID-19 infection, including a measure of socioeconomic deprivation, the group with one of these autoimmune diseases had an adjusted, statistically significant 23% increased risk of hospital death because of COVID-19 infection.

“This is the largest study of its kind to date. There’s potential for unmeasured confounding and selection bias here due to who gets tested. We’ll have to see where this study lands, but I think it does suggest there’s a slightly higher mortality risk in COVID-infected patients with rheumatic disease,” according to Dr. Yazdany.

On the other hand, there have been at least eight recently published patient surveys and case series of patients with rheumatic diseases in areas of the world hardest hit by the pandemic, and they paint a consistent picture.

“What we’ve learned from these studies was the infection rate was generally in the ballpark of people in the region. It doesn’t seem like there’s a dramatically higher infection rate in people with rheumatic disease in these surveys. The hospitalized rheumatology patients had many of the familiar comorbidities. This is the first glance at how likely people are to become infected and how they fared, and I think overall the data have been quite reassuring,” she said.

Dr. Yazdany reported serving as a consultant to AstraZeneca and Eli Lilly and receiving research funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention.

[email protected]

Patients on a tumor necrosis factor inhibitor for their rheumatic disease when they became infected with COVID-19 were markedly less likely to subsequently require hospitalization, according to intriguing early evidence from the COVID-19 Global Rheumatology Alliance Registry.

On the other hand, those registry patients who were on 10 mg of prednisone or more daily when they got infected were more than twice as likely to be hospitalized than were those who were not on corticosteroids, even after controlling for the severity of their rheumatic disease and other potential confounders, Jinoos Yazdany, MD, reported at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

“We saw a signal with moderate to high-dose steroids. I think it’s something we’re going to have to keep an eye out on as more data come in,” said Dr. Yazdany, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital.

The global registry launched on March 24, 2020, and was quickly embraced by rheumatologists from around the world. By May 12, the registry included more than 1,300 patients with a range of rheumatic diseases, all with confirmed COVID-19 infection as a requisite for enrollment; the cases were submitted by more than 300 rheumatologists in 40 countries. The registry is supported by the ACR and European League Against Rheumatism.

Dr. Yazdany, a member of the registry steering committee, described the project’s two main goals: To learn the outcomes of COVID-19–infected patients with various rheumatic diseases and to make inferences regarding the impact of the immunosuppressive and antimalarial medications widely prescribed by rheumatologists.

She presented soon-to-be-published data on the characteristics and disposition of the first 600 patients, 46% of whom were hospitalized and 9% died. A caveat regarding the registry, she noted, is that these are observational data and thus potentially subject to unrecognized confounders. Also, the registry population is skewed toward the sicker end of the COVID-19 disease spectrum because while all participants have confirmed infection, testing for the infection has been notoriously uneven. Many people are infected asymptomatically and thus may not undergo testing even where readily available.
 

Early key findings from registry

The risk factors for more severe infection resulting in hospitalization in patients with rheumatic diseases are by and large the same drivers described in the general population: older age and comorbid conditions including diabetes, hypertension, cardiovascular disease, obesity, chronic kidney disease, and lung disease. Notably, however, patients on the equivalent of 10 mg/day of prednisone or more were at a 105% increased risk for hospitalization, compared with those not on corticosteroids after adjustment for age, comorbid conditions, and rheumatic disease severity.

Patients on a background tumor necrosis factor (TNF) inhibitor had an adjusted 60% reduction in risk of hospitalization. This apparent protective effect against more severe COVID-19 disease is mechanistically plausible: In animal studies, being on a TNF inhibitor has been associated with less severe infection following exposure to influenza virus, Dr. Yazdany observed.

COVID-infected patients on any biologic disease-modifying antirheumatic drug had a 54% decreased risk of hospitalization. However, in this early analysis, the study was sufficiently powered only to specifically assess the impact of TNF inhibitors, since those agents were by far the most commonly used biologics. As the registry grows, it will be possible to analyze the impact of other antirheumatic medications.

Being on hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization.

The only rheumatic disease diagnosis with an odds of hospitalization significantly different from that of RA patients was systemic lupus erythematosus (SLE). Lupus patients were at 80% increased risk of hospitalization. Although this was a statistically significant difference, Dr. Yazdany cautioned against making too much of it because of the strong potential for unmeasured confounding. In particular, lupus patients as a group are known to rate on the lower end of measures of social determinants of health, a status that is an established major risk factor for COVID-19 disease.

“A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” she said.

Being on background NSAIDs at the time of SARS-CoV-2 infection was not associated with increased risk of hospitalization; in fact, NSAID users were 36% less likely to be hospitalized for their COVID-19 disease, although this difference didn’t reach statistical significance.

Dr. Yazdany urged her fellow rheumatologists to enter their cases on the registry website: rheum-covid.org. There they can also join the registry mailing list and receive weekly updates.
 

Other recent insights on COVID-19 in rheumatology

An as-yet unpublished U.K. observational study involving electronic health record data on 17 million people included 885,000 individuals with RA, SLE, or psoriasis. After extensive statistical controlling for the known risk factors for severe COVID-19 infection, including a measure of socioeconomic deprivation, the group with one of these autoimmune diseases had an adjusted, statistically significant 23% increased risk of hospital death because of COVID-19 infection.

“This is the largest study of its kind to date. There’s potential for unmeasured confounding and selection bias here due to who gets tested. We’ll have to see where this study lands, but I think it does suggest there’s a slightly higher mortality risk in COVID-infected patients with rheumatic disease,” according to Dr. Yazdany.

On the other hand, there have been at least eight recently published patient surveys and case series of patients with rheumatic diseases in areas of the world hardest hit by the pandemic, and they paint a consistent picture.

“What we’ve learned from these studies was the infection rate was generally in the ballpark of people in the region. It doesn’t seem like there’s a dramatically higher infection rate in people with rheumatic disease in these surveys. The hospitalized rheumatology patients had many of the familiar comorbidities. This is the first glance at how likely people are to become infected and how they fared, and I think overall the data have been quite reassuring,” she said.

Dr. Yazdany reported serving as a consultant to AstraZeneca and Eli Lilly and receiving research funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention.

[email protected]

Patients on a tumor necrosis factor inhibitor for their rheumatic disease when they became infected with COVID-19 were markedly less likely to subsequently require hospitalization, according to intriguing early evidence from the COVID-19 Global Rheumatology Alliance Registry.

On the other hand, those registry patients who were on 10 mg of prednisone or more daily when they got infected were more than twice as likely to be hospitalized than were those who were not on corticosteroids, even after controlling for the severity of their rheumatic disease and other potential confounders, Jinoos Yazdany, MD, reported at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

“We saw a signal with moderate to high-dose steroids. I think it’s something we’re going to have to keep an eye out on as more data come in,” said Dr. Yazdany, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital.

The global registry launched on March 24, 2020, and was quickly embraced by rheumatologists from around the world. By May 12, the registry included more than 1,300 patients with a range of rheumatic diseases, all with confirmed COVID-19 infection as a requisite for enrollment; the cases were submitted by more than 300 rheumatologists in 40 countries. The registry is supported by the ACR and European League Against Rheumatism.

Dr. Yazdany, a member of the registry steering committee, described the project’s two main goals: To learn the outcomes of COVID-19–infected patients with various rheumatic diseases and to make inferences regarding the impact of the immunosuppressive and antimalarial medications widely prescribed by rheumatologists.

She presented soon-to-be-published data on the characteristics and disposition of the first 600 patients, 46% of whom were hospitalized and 9% died. A caveat regarding the registry, she noted, is that these are observational data and thus potentially subject to unrecognized confounders. Also, the registry population is skewed toward the sicker end of the COVID-19 disease spectrum because while all participants have confirmed infection, testing for the infection has been notoriously uneven. Many people are infected asymptomatically and thus may not undergo testing even where readily available.
 

Early key findings from registry

The risk factors for more severe infection resulting in hospitalization in patients with rheumatic diseases are by and large the same drivers described in the general population: older age and comorbid conditions including diabetes, hypertension, cardiovascular disease, obesity, chronic kidney disease, and lung disease. Notably, however, patients on the equivalent of 10 mg/day of prednisone or more were at a 105% increased risk for hospitalization, compared with those not on corticosteroids after adjustment for age, comorbid conditions, and rheumatic disease severity.

Patients on a background tumor necrosis factor (TNF) inhibitor had an adjusted 60% reduction in risk of hospitalization. This apparent protective effect against more severe COVID-19 disease is mechanistically plausible: In animal studies, being on a TNF inhibitor has been associated with less severe infection following exposure to influenza virus, Dr. Yazdany observed.

COVID-infected patients on any biologic disease-modifying antirheumatic drug had a 54% decreased risk of hospitalization. However, in this early analysis, the study was sufficiently powered only to specifically assess the impact of TNF inhibitors, since those agents were by far the most commonly used biologics. As the registry grows, it will be possible to analyze the impact of other antirheumatic medications.

Being on hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization.

The only rheumatic disease diagnosis with an odds of hospitalization significantly different from that of RA patients was systemic lupus erythematosus (SLE). Lupus patients were at 80% increased risk of hospitalization. Although this was a statistically significant difference, Dr. Yazdany cautioned against making too much of it because of the strong potential for unmeasured confounding. In particular, lupus patients as a group are known to rate on the lower end of measures of social determinants of health, a status that is an established major risk factor for COVID-19 disease.

“A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” she said.

Being on background NSAIDs at the time of SARS-CoV-2 infection was not associated with increased risk of hospitalization; in fact, NSAID users were 36% less likely to be hospitalized for their COVID-19 disease, although this difference didn’t reach statistical significance.

Dr. Yazdany urged her fellow rheumatologists to enter their cases on the registry website: rheum-covid.org. There they can also join the registry mailing list and receive weekly updates.
 

Other recent insights on COVID-19 in rheumatology

An as-yet unpublished U.K. observational study involving electronic health record data on 17 million people included 885,000 individuals with RA, SLE, or psoriasis. After extensive statistical controlling for the known risk factors for severe COVID-19 infection, including a measure of socioeconomic deprivation, the group with one of these autoimmune diseases had an adjusted, statistically significant 23% increased risk of hospital death because of COVID-19 infection.

“This is the largest study of its kind to date. There’s potential for unmeasured confounding and selection bias here due to who gets tested. We’ll have to see where this study lands, but I think it does suggest there’s a slightly higher mortality risk in COVID-infected patients with rheumatic disease,” according to Dr. Yazdany.

On the other hand, there have been at least eight recently published patient surveys and case series of patients with rheumatic diseases in areas of the world hardest hit by the pandemic, and they paint a consistent picture.

“What we’ve learned from these studies was the infection rate was generally in the ballpark of people in the region. It doesn’t seem like there’s a dramatically higher infection rate in people with rheumatic disease in these surveys. The hospitalized rheumatology patients had many of the familiar comorbidities. This is the first glance at how likely people are to become infected and how they fared, and I think overall the data have been quite reassuring,” she said.

Dr. Yazdany reported serving as a consultant to AstraZeneca and Eli Lilly and receiving research funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention.

[email protected]

A large-scale screen of urine proteins has identified molecules that may help to determine whether a patient has active lupus nephritis, according to a cross-sectional study published in Nature Communications. The proteins that best differentiate active lupus nephritis from inactive systemic lupus erythematosus (SLE) vary across ethnicities, the researchers wrote.

“A longitudinal study is warranted to investigate how these molecules relate to disease pathology and progression over time,” said senior study author Chandra Mohan, MD, PhD, of the department of biomedical engineering at the University of Houston, and colleagues. In addition, researchers should investigate the roles of protein biomarkers ALCAM, PF-4, properdin, VCAM-1, and sE-selectin in mediating lupus nephritis.
 

Limitations of renal biopsy

About 60% of patients with SLE will develop lupus nephritis, and 10%-15% of patients who develop lupus nephritis progress to end-stage renal disease. Although renal biopsy is the gold standard for the diagnosis of renal involvement in SLE, biopsies are invasive, not serially repeatable, and may not represent the entire kidney, Dr. Mohan and colleagues wrote.

To identify potential urinary biomarkers of lupus nephritis using an unbiased, proteomic approach, the investigators screened urine samples from 23 participants – 7 with active lupus nephritis, 8 with inactive SLE, and 8 healthy controls. They used an aptamer-based screen to investigate more than 1,100 proteins. The researchers then validated biomarker candidates using enzyme-linked immunosorbent assays. Independent cross-sectional cohorts included 127 patients with inactive SLE, 107 patients with active lupus nephritis, 67 patients with active nonrenal lupus, and 74 healthy controls. The cohorts included patients who were African American, Caucasian, and Asian. The researchers excluded patients with renal failure and pediatric patients.

Of the 12 urine proteins studied, 10 outperformed traditional laboratory measures, such as C3/C4 and anti–double stranded DNA, in discriminating active lupus nephritis from inactive SLE, wrote Dr. Mohan and colleagues. A Lasso regression analysis found that the best predictive model included 8 of the 12 urine proteins as well as race. The model discriminated active lupus nephritis from inactive SLE with an area under the receiver operating characteristic curve (AUC) of 0.98.

Among African Americans, urine proteins that best distinguished active lupus nephritis from inactive disease included PF-4 (AUC, 0.88), VCAM-1 (AUC, 0.87), properdin (AUC, 0.85), and ALCAM (AUC, 0.84). Among Caucasians, they included sE-selectin (AUC, 0.87), VCAM-1 (AUC, 0.84), BFL-1 (AUC, 0.81), and hemopexin (AUC, 0.80). Among Asians, they included ALCAM (AUC, 0.93), VCAM-1 (AUC, 0.92), TFPI (AUC, 0.88), and PF-4 (AUC, 0.83).

The study is “unique in highlighting the importance of tailoring the biomarkers to patient ethnicity,” the researchers wrote.

Basing subgroups on race rather than phenotypic profiles

“This is an important study because it confirms the ability to predict active lupus nephritis from urine samples and utilized advanced technologies to find key markers for that,” said Joan T. Merrill, MD, of the Oklahoma Medical Research Foundation in Oklahoma City. “It is unfortunate that investigators with access to such advanced technology are still using an outdated and extremely questionable method for distinguishing subgroups of patients, that of race.”

Grouping patients by phenotypic profiles that reflect current disease states “would be a more accurate method for finding optimal urinary markers for active nephritis,” and is “likely to prove more accurate for individuals in all races,” Dr. Merrill said. Certain racial subgroups may be more likely to have particular disease phenotypes, “which are usually identified based on gene pathway coexpression patterns.” Still, “people who self-identify as a given race are not genetically identical,” Dr. Merrill added. “In fact, this is a very blunt instrument, compared to phenotypic profiling now available for lupus patients.”

SLE and lupus nephritis are “heavily influenced by genetics,” and African Americans are three times more likely than Caucasians to develop SLE and are more like to develop end-stage renal disease, Dr. Mohan and colleagues wrote. Nevertheless, “influence from environmental triggers or socioeconomic factors cannot be ruled out,” they added. “Although patient demographics are widely known to affect SLE disease manifestations and outcomes, there are virtually no studies investigating this phenomenon in the context of disease biomarkers; most SLE biomarkers studies focus on one demographic group or all ethnic groups combined, which yield results that may not be equally predictive in all demographic groups of SLE patients.”

Dr. Mohan is collaborating with a biotechnology company to study drugs that may block ALCAM, according to a University of Houston news release. ALCAM is involved in immune and inflammatory responses, the researchers noted. “When all SLE patients were combined, urine ALCAM levels had the strongest bearing on disease activity status, in an unsupervised Bayesian network analysis,” they wrote. “Urine ALCAM also emerged as one of the few proteins that distinguished active [lupus nephritis] from active nonrenal lupus.”

National Institutes of Health grants supported the research. The investigators had no competing interests.
 

[email protected]

SOURCE: Stanley S et al. Nat Commun. 2020 May 4. doi: 10.1038/s41467-020-15986-3.

A large-scale screen of urine proteins has identified molecules that may help to determine whether a patient has active lupus nephritis, according to a cross-sectional study published in Nature Communications. The proteins that best differentiate active lupus nephritis from inactive systemic lupus erythematosus (SLE) vary across ethnicities, the researchers wrote.

“A longitudinal study is warranted to investigate how these molecules relate to disease pathology and progression over time,” said senior study author Chandra Mohan, MD, PhD, of the department of biomedical engineering at the University of Houston, and colleagues. In addition, researchers should investigate the roles of protein biomarkers ALCAM, PF-4, properdin, VCAM-1, and sE-selectin in mediating lupus nephritis.
 

Limitations of renal biopsy

About 60% of patients with SLE will develop lupus nephritis, and 10%-15% of patients who develop lupus nephritis progress to end-stage renal disease. Although renal biopsy is the gold standard for the diagnosis of renal involvement in SLE, biopsies are invasive, not serially repeatable, and may not represent the entire kidney, Dr. Mohan and colleagues wrote.

To identify potential urinary biomarkers of lupus nephritis using an unbiased, proteomic approach, the investigators screened urine samples from 23 participants – 7 with active lupus nephritis, 8 with inactive SLE, and 8 healthy controls. They used an aptamer-based screen to investigate more than 1,100 proteins. The researchers then validated biomarker candidates using enzyme-linked immunosorbent assays. Independent cross-sectional cohorts included 127 patients with inactive SLE, 107 patients with active lupus nephritis, 67 patients with active nonrenal lupus, and 74 healthy controls. The cohorts included patients who were African American, Caucasian, and Asian. The researchers excluded patients with renal failure and pediatric patients.

Of the 12 urine proteins studied, 10 outperformed traditional laboratory measures, such as C3/C4 and anti–double stranded DNA, in discriminating active lupus nephritis from inactive SLE, wrote Dr. Mohan and colleagues. A Lasso regression analysis found that the best predictive model included 8 of the 12 urine proteins as well as race. The model discriminated active lupus nephritis from inactive SLE with an area under the receiver operating characteristic curve (AUC) of 0.98.

Among African Americans, urine proteins that best distinguished active lupus nephritis from inactive disease included PF-4 (AUC, 0.88), VCAM-1 (AUC, 0.87), properdin (AUC, 0.85), and ALCAM (AUC, 0.84). Among Caucasians, they included sE-selectin (AUC, 0.87), VCAM-1 (AUC, 0.84), BFL-1 (AUC, 0.81), and hemopexin (AUC, 0.80). Among Asians, they included ALCAM (AUC, 0.93), VCAM-1 (AUC, 0.92), TFPI (AUC, 0.88), and PF-4 (AUC, 0.83).

The study is “unique in highlighting the importance of tailoring the biomarkers to patient ethnicity,” the researchers wrote.

Basing subgroups on race rather than phenotypic profiles

“This is an important study because it confirms the ability to predict active lupus nephritis from urine samples and utilized advanced technologies to find key markers for that,” said Joan T. Merrill, MD, of the Oklahoma Medical Research Foundation in Oklahoma City. “It is unfortunate that investigators with access to such advanced technology are still using an outdated and extremely questionable method for distinguishing subgroups of patients, that of race.”

Grouping patients by phenotypic profiles that reflect current disease states “would be a more accurate method for finding optimal urinary markers for active nephritis,” and is “likely to prove more accurate for individuals in all races,” Dr. Merrill said. Certain racial subgroups may be more likely to have particular disease phenotypes, “which are usually identified based on gene pathway coexpression patterns.” Still, “people who self-identify as a given race are not genetically identical,” Dr. Merrill added. “In fact, this is a very blunt instrument, compared to phenotypic profiling now available for lupus patients.”

SLE and lupus nephritis are “heavily influenced by genetics,” and African Americans are three times more likely than Caucasians to develop SLE and are more like to develop end-stage renal disease, Dr. Mohan and colleagues wrote. Nevertheless, “influence from environmental triggers or socioeconomic factors cannot be ruled out,” they added. “Although patient demographics are widely known to affect SLE disease manifestations and outcomes, there are virtually no studies investigating this phenomenon in the context of disease biomarkers; most SLE biomarkers studies focus on one demographic group or all ethnic groups combined, which yield results that may not be equally predictive in all demographic groups of SLE patients.”

Dr. Mohan is collaborating with a biotechnology company to study drugs that may block ALCAM, according to a University of Houston news release. ALCAM is involved in immune and inflammatory responses, the researchers noted. “When all SLE patients were combined, urine ALCAM levels had the strongest bearing on disease activity status, in an unsupervised Bayesian network analysis,” they wrote. “Urine ALCAM also emerged as one of the few proteins that distinguished active [lupus nephritis] from active nonrenal lupus.”

National Institutes of Health grants supported the research. The investigators had no competing interests.
 

[email protected]

SOURCE: Stanley S et al. Nat Commun. 2020 May 4. doi: 10.1038/s41467-020-15986-3.

A large-scale screen of urine proteins has identified molecules that may help to determine whether a patient has active lupus nephritis, according to a cross-sectional study published in Nature Communications. The proteins that best differentiate active lupus nephritis from inactive systemic lupus erythematosus (SLE) vary across ethnicities, the researchers wrote.

“A longitudinal study is warranted to investigate how these molecules relate to disease pathology and progression over time,” said senior study author Chandra Mohan, MD, PhD, of the department of biomedical engineering at the University of Houston, and colleagues. In addition, researchers should investigate the roles of protein biomarkers ALCAM, PF-4, properdin, VCAM-1, and sE-selectin in mediating lupus nephritis.
 

Limitations of renal biopsy

About 60% of patients with SLE will develop lupus nephritis, and 10%-15% of patients who develop lupus nephritis progress to end-stage renal disease. Although renal biopsy is the gold standard for the diagnosis of renal involvement in SLE, biopsies are invasive, not serially repeatable, and may not represent the entire kidney, Dr. Mohan and colleagues wrote.

To identify potential urinary biomarkers of lupus nephritis using an unbiased, proteomic approach, the investigators screened urine samples from 23 participants – 7 with active lupus nephritis, 8 with inactive SLE, and 8 healthy controls. They used an aptamer-based screen to investigate more than 1,100 proteins. The researchers then validated biomarker candidates using enzyme-linked immunosorbent assays. Independent cross-sectional cohorts included 127 patients with inactive SLE, 107 patients with active lupus nephritis, 67 patients with active nonrenal lupus, and 74 healthy controls. The cohorts included patients who were African American, Caucasian, and Asian. The researchers excluded patients with renal failure and pediatric patients.

Of the 12 urine proteins studied, 10 outperformed traditional laboratory measures, such as C3/C4 and anti–double stranded DNA, in discriminating active lupus nephritis from inactive SLE, wrote Dr. Mohan and colleagues. A Lasso regression analysis found that the best predictive model included 8 of the 12 urine proteins as well as race. The model discriminated active lupus nephritis from inactive SLE with an area under the receiver operating characteristic curve (AUC) of 0.98.

Among African Americans, urine proteins that best distinguished active lupus nephritis from inactive disease included PF-4 (AUC, 0.88), VCAM-1 (AUC, 0.87), properdin (AUC, 0.85), and ALCAM (AUC, 0.84). Among Caucasians, they included sE-selectin (AUC, 0.87), VCAM-1 (AUC, 0.84), BFL-1 (AUC, 0.81), and hemopexin (AUC, 0.80). Among Asians, they included ALCAM (AUC, 0.93), VCAM-1 (AUC, 0.92), TFPI (AUC, 0.88), and PF-4 (AUC, 0.83).

The study is “unique in highlighting the importance of tailoring the biomarkers to patient ethnicity,” the researchers wrote.

Basing subgroups on race rather than phenotypic profiles

“This is an important study because it confirms the ability to predict active lupus nephritis from urine samples and utilized advanced technologies to find key markers for that,” said Joan T. Merrill, MD, of the Oklahoma Medical Research Foundation in Oklahoma City. “It is unfortunate that investigators with access to such advanced technology are still using an outdated and extremely questionable method for distinguishing subgroups of patients, that of race.”

Grouping patients by phenotypic profiles that reflect current disease states “would be a more accurate method for finding optimal urinary markers for active nephritis,” and is “likely to prove more accurate for individuals in all races,” Dr. Merrill said. Certain racial subgroups may be more likely to have particular disease phenotypes, “which are usually identified based on gene pathway coexpression patterns.” Still, “people who self-identify as a given race are not genetically identical,” Dr. Merrill added. “In fact, this is a very blunt instrument, compared to phenotypic profiling now available for lupus patients.”

SLE and lupus nephritis are “heavily influenced by genetics,” and African Americans are three times more likely than Caucasians to develop SLE and are more like to develop end-stage renal disease, Dr. Mohan and colleagues wrote. Nevertheless, “influence from environmental triggers or socioeconomic factors cannot be ruled out,” they added. “Although patient demographics are widely known to affect SLE disease manifestations and outcomes, there are virtually no studies investigating this phenomenon in the context of disease biomarkers; most SLE biomarkers studies focus on one demographic group or all ethnic groups combined, which yield results that may not be equally predictive in all demographic groups of SLE patients.”

Dr. Mohan is collaborating with a biotechnology company to study drugs that may block ALCAM, according to a University of Houston news release. ALCAM is involved in immune and inflammatory responses, the researchers noted. “When all SLE patients were combined, urine ALCAM levels had the strongest bearing on disease activity status, in an unsupervised Bayesian network analysis,” they wrote. “Urine ALCAM also emerged as one of the few proteins that distinguished active [lupus nephritis] from active nonrenal lupus.”

National Institutes of Health grants supported the research. The investigators had no competing interests.
 

[email protected]

SOURCE: Stanley S et al. Nat Commun. 2020 May 4. doi: 10.1038/s41467-020-15986-3.

The COVID-19 pandemic continues to pose an unprecedented challenge to health care systems worldwide. In addition to the direct impact of the disease itself, there is a growing concern related to ensuring adequate health care utilization and addressing the needs of vulnerable populations, such as those with chronic illness.

Emanuel et al. have advocated a framework of fair allocation of resources, led by the principles of equity, maximizing benefits, and prioritizing the vulnerable. In these uncertain times, patients with rheumatic diseases represent a vulnerable population whose health and wellness are particularly threatened, not only by the risk of COVID-19, but also by reduced access to usual medical care (e.g., in-person clinic visits), potential treatment interruptions (e.g., planned infusion therapies), and the ongoing shortage of hydroxychloroquine, to name a few.

As rheumatologists, we are now tasked with the development of best practices for caring for patients with rheumatic conditions in this uncertain, evolving, and nearly data-free landscape. We also must maintain an active role as advocates for our patients to help them navigate this pandemic. Herein, we discuss our approach to caring for patients with rheumatic diseases within our practice in New York City, an epicenter of the COVID-19 pandemic.

Communication with patients

Maintaining an open line of communication with our patients (by phone, patient portal, telemedicine, and so on) has become more essential than ever. It is through these communications that we best understand our patients’ concerns and provide support and personalized treatment decisions. The most common questions we have received during recent weeks are:

• Should I stop my medication to lower my risk for infection?
• Are my current symptoms caused by coronavirus, and what should I do next?
• Where can I fill my hydroxychloroquine prescription?

The American College of Rheumatology has deployed a number of task forces aimed at advocating for rheumatologists and patients with rheumatic diseases and is doing an exemplary job guiding us. For patients, several other organizations (e.g., CreakyJoints, Arthritis Foundation, Lupus Research Alliance, Vasculitis Foundation, and Scleroderma Foundation) are also providing accurate information regarding hygiene practices, social distancing, management of medications, and other guidance related to specific rheumatic diseases. In line with ACR recommendations, we encourage a personalized, shared decision-making process with each of our patients.

Patients with rheumatic disease at risk for COVID-19 infection

First, for rheumatology patients who have no COVID-19 symptoms, our management approach is individualized. For patients who are able to maintain social distancing, we have not routinely stopped immunosuppressive medications, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents. However, we discuss the risks and benefits of continuing immunosuppressive therapy during this time with all of our patients.

In certain cases of stable, non–life-threatening disease, we may consider spacing or temporarily interrupting immunosuppressive therapy, using individualized, shared decision making. Yet, it is important to recognize that, for some patients, achieving adequate disease control can require a substantial amount of time.

Furthermore, it is important to acknowledge that disease flares requiring steroid therapy may increase the risk for infection even more, keeping in mind that, in some rheumatic diseases, high disease activity itself can increase infection risk. We advise patients who are continuing therapy to maintain at least a 1-month supply of their medications.

Decisions regarding infusions in the hospital and outpatient settings are similarly made on an individual basis, weighing the risk for virus exposure against that of disease flare. The more limited availability of appropriately distanced infusion chairs in some already overburdened systems must be considered in this discussion. We agree with the ACR, whose infusion guidance recommends that “possible changes might include temporary interruption of therapy, temporary initiation of a bridge therapy such as a less potent anti-inflammatory or immune-modulating agent, or temporary change to an alternative therapy.”

We also reinforce recommended behaviors for preventing infection, including social distancing, frequent handwashing, and avoiding touching one’s face.

Patients with rheumatic disease and confirmed or suspected COVID-19 infection

With the worldwide spread of COVID-19, patients with rheumatic diseases will undoubtedly be among those exposed and infected. Though current data are limited, within a cohort from China, 1% had an autoimmune disease. Testing recommendations to confirm COVID-19 and decision guidelines for outpatient versus inpatient management are evolving, and we consult the most up-to-date, local information regarding testing as individual potential cases arise.

For patients who develop COVID-19 and are currently taking DMARDs and biologics, we recommend that they discontinue these medications, with the exception of hydroxychloroquine (HCQ). HCQ may be continued because its mechanism is not expected to worsen infection, and it plays a key role in the management of patients with systemic lupus erythematosus (SLE). In addition, in vitro antiviral effects have been reported and there is growing interest for its use in the management of COVID-19. However, there are conflicting data and methodological concerns about the nonrandomized human studies that suggest a benefit of HCQ against COVID-19.

The decision regarding management of glucocorticoids in the setting of new COVID-19 infection is challenging and should be individualized. At present, expert panels recommend against the use of glucocorticoids among individuals with COVID-19 who do not have acute respiratory distress syndrome. However, adrenal insufficiency must be considered among patients with COVID-19 who are treated with chronic glucocorticoids. Again, these decisions should be made on an individual, case-by-case basis.

Implications of a hydroxychloroquine shortage

The use of HCQ in rheumatology is supported by years of research. Particularly in SLE, HCQ has been shown to reduce disease activity and damage and to improve survival. Furthermore, for pregnant patients with SLE, numerous studies have demonstrated the safety and benefit of HCQ for both the mother and fetus; thus, it is strongly recommended. By contrast, despite the growing interest for HCQ in patients with COVID-19, the evidence is inconclusive and limited.

The ACR suggests that decisions regarding HCQ dose reductions to extend individual patients supplies should be tailored to each patient’s need and risk in the unfortunate setting of medication shortages. Even in patients with stable SLE, however, disease flares at 6 months are more common among individuals who discontinue HCQ. Of note, these flares may incorporate novel and severe disease manifestations.

Unfortunately, other therapeutic options for SLE are associated with more adverse effects (including increased susceptibility to infection) or are largely unavailable (e.g., quinacrine). Thus, we strive to continue standard dosing of HCQ for patients who are currently flaring or recently flared, and we make shared, individualized decisions for those patients with stable disease as the HCQ shortage evolves.

Future research on COVID-19 and rheumatic disease

While we might expect that an underlying rheumatic disease and associated treatments may predispose individuals to developing COVID-19, current data do not indicate which, if any, rheumatic diseases and associated therapies convey the greatest risk.

To address this uncertainty, the rheumatology community created the COVID-19 Global Rheumatology Alliance, an international effort to initiate and maintain a deidentified patient registry for individuals with rheumatic disease who develop COVID-19. These efforts will allow us to gain essential insights regarding which patient demographics, underlying diseases, and medications are most common among patients who develop COVID-19.

This alliance encourages rheumatologists and those caring for patients with rheumatic diseases to report their patient cases to this registry. As we are confronted with making management decisions with a scarcity of supporting data, efforts like these will improve our ability to make individualized treatment recommendations.

The COVID-19 pandemic has presented us all with unprecedented challenges. As rheumatologists, it is our duty to lead our patients through this uncharted territory with close communication, information, advocacy, and personalized treatment decisions. Each of these is central to the management of rheumatology patients during the COVID-19 pandemic.

With the growing interest in immunomodulatory therapies for the complications of this infection, we have the unique opportunity to share our expertise, recommendations, and caution with our colleagues. As clinicians and scientists, we must advocate for data collection and studies that will allow us to develop novel, data-driven disease management approaches while providing the best care possible for our patients.

Stephen Paget, MD, is physician in chief emeritus for the Center for Rheumatology at Hospital for Special Surgery in New York. Kimberly Showalter, MD, is a third-year rheumatology fellow at Hospital for Special Surgery. Sebastian E. Sattui, MD, is a third-year rheumatology and 1-year vasculitis fellow at Hospital for Special Surgery.

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

The COVID-19 pandemic continues to pose an unprecedented challenge to health care systems worldwide. In addition to the direct impact of the disease itself, there is a growing concern related to ensuring adequate health care utilization and addressing the needs of vulnerable populations, such as those with chronic illness.

Emanuel et al. have advocated a framework of fair allocation of resources, led by the principles of equity, maximizing benefits, and prioritizing the vulnerable. In these uncertain times, patients with rheumatic diseases represent a vulnerable population whose health and wellness are particularly threatened, not only by the risk of COVID-19, but also by reduced access to usual medical care (e.g., in-person clinic visits), potential treatment interruptions (e.g., planned infusion therapies), and the ongoing shortage of hydroxychloroquine, to name a few.

As rheumatologists, we are now tasked with the development of best practices for caring for patients with rheumatic conditions in this uncertain, evolving, and nearly data-free landscape. We also must maintain an active role as advocates for our patients to help them navigate this pandemic. Herein, we discuss our approach to caring for patients with rheumatic diseases within our practice in New York City, an epicenter of the COVID-19 pandemic.

Communication with patients

Maintaining an open line of communication with our patients (by phone, patient portal, telemedicine, and so on) has become more essential than ever. It is through these communications that we best understand our patients’ concerns and provide support and personalized treatment decisions. The most common questions we have received during recent weeks are:

• Should I stop my medication to lower my risk for infection?
• Are my current symptoms caused by coronavirus, and what should I do next?
• Where can I fill my hydroxychloroquine prescription?

The American College of Rheumatology has deployed a number of task forces aimed at advocating for rheumatologists and patients with rheumatic diseases and is doing an exemplary job guiding us. For patients, several other organizations (e.g., CreakyJoints, Arthritis Foundation, Lupus Research Alliance, Vasculitis Foundation, and Scleroderma Foundation) are also providing accurate information regarding hygiene practices, social distancing, management of medications, and other guidance related to specific rheumatic diseases. In line with ACR recommendations, we encourage a personalized, shared decision-making process with each of our patients.

Patients with rheumatic disease at risk for COVID-19 infection

First, for rheumatology patients who have no COVID-19 symptoms, our management approach is individualized. For patients who are able to maintain social distancing, we have not routinely stopped immunosuppressive medications, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents. However, we discuss the risks and benefits of continuing immunosuppressive therapy during this time with all of our patients.

In certain cases of stable, non–life-threatening disease, we may consider spacing or temporarily interrupting immunosuppressive therapy, using individualized, shared decision making. Yet, it is important to recognize that, for some patients, achieving adequate disease control can require a substantial amount of time.

Furthermore, it is important to acknowledge that disease flares requiring steroid therapy may increase the risk for infection even more, keeping in mind that, in some rheumatic diseases, high disease activity itself can increase infection risk. We advise patients who are continuing therapy to maintain at least a 1-month supply of their medications.

Decisions regarding infusions in the hospital and outpatient settings are similarly made on an individual basis, weighing the risk for virus exposure against that of disease flare. The more limited availability of appropriately distanced infusion chairs in some already overburdened systems must be considered in this discussion. We agree with the ACR, whose infusion guidance recommends that “possible changes might include temporary interruption of therapy, temporary initiation of a bridge therapy such as a less potent anti-inflammatory or immune-modulating agent, or temporary change to an alternative therapy.”

We also reinforce recommended behaviors for preventing infection, including social distancing, frequent handwashing, and avoiding touching one’s face.

Patients with rheumatic disease and confirmed or suspected COVID-19 infection

With the worldwide spread of COVID-19, patients with rheumatic diseases will undoubtedly be among those exposed and infected. Though current data are limited, within a cohort from China, 1% had an autoimmune disease. Testing recommendations to confirm COVID-19 and decision guidelines for outpatient versus inpatient management are evolving, and we consult the most up-to-date, local information regarding testing as individual potential cases arise.

For patients who develop COVID-19 and are currently taking DMARDs and biologics, we recommend that they discontinue these medications, with the exception of hydroxychloroquine (HCQ). HCQ may be continued because its mechanism is not expected to worsen infection, and it plays a key role in the management of patients with systemic lupus erythematosus (SLE). In addition, in vitro antiviral effects have been reported and there is growing interest for its use in the management of COVID-19. However, there are conflicting data and methodological concerns about the nonrandomized human studies that suggest a benefit of HCQ against COVID-19.

The decision regarding management of glucocorticoids in the setting of new COVID-19 infection is challenging and should be individualized. At present, expert panels recommend against the use of glucocorticoids among individuals with COVID-19 who do not have acute respiratory distress syndrome. However, adrenal insufficiency must be considered among patients with COVID-19 who are treated with chronic glucocorticoids. Again, these decisions should be made on an individual, case-by-case basis.

Implications of a hydroxychloroquine shortage

The use of HCQ in rheumatology is supported by years of research. Particularly in SLE, HCQ has been shown to reduce disease activity and damage and to improve survival. Furthermore, for pregnant patients with SLE, numerous studies have demonstrated the safety and benefit of HCQ for both the mother and fetus; thus, it is strongly recommended. By contrast, despite the growing interest for HCQ in patients with COVID-19, the evidence is inconclusive and limited.

The ACR suggests that decisions regarding HCQ dose reductions to extend individual patients supplies should be tailored to each patient’s need and risk in the unfortunate setting of medication shortages. Even in patients with stable SLE, however, disease flares at 6 months are more common among individuals who discontinue HCQ. Of note, these flares may incorporate novel and severe disease manifestations.

Unfortunately, other therapeutic options for SLE are associated with more adverse effects (including increased susceptibility to infection) or are largely unavailable (e.g., quinacrine). Thus, we strive to continue standard dosing of HCQ for patients who are currently flaring or recently flared, and we make shared, individualized decisions for those patients with stable disease as the HCQ shortage evolves.

Future research on COVID-19 and rheumatic disease

While we might expect that an underlying rheumatic disease and associated treatments may predispose individuals to developing COVID-19, current data do not indicate which, if any, rheumatic diseases and associated therapies convey the greatest risk.

To address this uncertainty, the rheumatology community created the COVID-19 Global Rheumatology Alliance, an international effort to initiate and maintain a deidentified patient registry for individuals with rheumatic disease who develop COVID-19. These efforts will allow us to gain essential insights regarding which patient demographics, underlying diseases, and medications are most common among patients who develop COVID-19.

This alliance encourages rheumatologists and those caring for patients with rheumatic diseases to report their patient cases to this registry. As we are confronted with making management decisions with a scarcity of supporting data, efforts like these will improve our ability to make individualized treatment recommendations.

The COVID-19 pandemic has presented us all with unprecedented challenges. As rheumatologists, it is our duty to lead our patients through this uncharted territory with close communication, information, advocacy, and personalized treatment decisions. Each of these is central to the management of rheumatology patients during the COVID-19 pandemic.

With the growing interest in immunomodulatory therapies for the complications of this infection, we have the unique opportunity to share our expertise, recommendations, and caution with our colleagues. As clinicians and scientists, we must advocate for data collection and studies that will allow us to develop novel, data-driven disease management approaches while providing the best care possible for our patients.

Stephen Paget, MD, is physician in chief emeritus for the Center for Rheumatology at Hospital for Special Surgery in New York. Kimberly Showalter, MD, is a third-year rheumatology fellow at Hospital for Special Surgery. Sebastian E. Sattui, MD, is a third-year rheumatology and 1-year vasculitis fellow at Hospital for Special Surgery.

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

The COVID-19 pandemic continues to pose an unprecedented challenge to health care systems worldwide. In addition to the direct impact of the disease itself, there is a growing concern related to ensuring adequate health care utilization and addressing the needs of vulnerable populations, such as those with chronic illness.

Emanuel et al. have advocated a framework of fair allocation of resources, led by the principles of equity, maximizing benefits, and prioritizing the vulnerable. In these uncertain times, patients with rheumatic diseases represent a vulnerable population whose health and wellness are particularly threatened, not only by the risk of COVID-19, but also by reduced access to usual medical care (e.g., in-person clinic visits), potential treatment interruptions (e.g., planned infusion therapies), and the ongoing shortage of hydroxychloroquine, to name a few.

As rheumatologists, we are now tasked with the development of best practices for caring for patients with rheumatic conditions in this uncertain, evolving, and nearly data-free landscape. We also must maintain an active role as advocates for our patients to help them navigate this pandemic. Herein, we discuss our approach to caring for patients with rheumatic diseases within our practice in New York City, an epicenter of the COVID-19 pandemic.

Communication with patients

Maintaining an open line of communication with our patients (by phone, patient portal, telemedicine, and so on) has become more essential than ever. It is through these communications that we best understand our patients’ concerns and provide support and personalized treatment decisions. The most common questions we have received during recent weeks are:

• Should I stop my medication to lower my risk for infection?
• Are my current symptoms caused by coronavirus, and what should I do next?
• Where can I fill my hydroxychloroquine prescription?

The American College of Rheumatology has deployed a number of task forces aimed at advocating for rheumatologists and patients with rheumatic diseases and is doing an exemplary job guiding us. For patients, several other organizations (e.g., CreakyJoints, Arthritis Foundation, Lupus Research Alliance, Vasculitis Foundation, and Scleroderma Foundation) are also providing accurate information regarding hygiene practices, social distancing, management of medications, and other guidance related to specific rheumatic diseases. In line with ACR recommendations, we encourage a personalized, shared decision-making process with each of our patients.

Patients with rheumatic disease at risk for COVID-19 infection

First, for rheumatology patients who have no COVID-19 symptoms, our management approach is individualized. For patients who are able to maintain social distancing, we have not routinely stopped immunosuppressive medications, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents. However, we discuss the risks and benefits of continuing immunosuppressive therapy during this time with all of our patients.

In certain cases of stable, non–life-threatening disease, we may consider spacing or temporarily interrupting immunosuppressive therapy, using individualized, shared decision making. Yet, it is important to recognize that, for some patients, achieving adequate disease control can require a substantial amount of time.

Furthermore, it is important to acknowledge that disease flares requiring steroid therapy may increase the risk for infection even more, keeping in mind that, in some rheumatic diseases, high disease activity itself can increase infection risk. We advise patients who are continuing therapy to maintain at least a 1-month supply of their medications.

Decisions regarding infusions in the hospital and outpatient settings are similarly made on an individual basis, weighing the risk for virus exposure against that of disease flare. The more limited availability of appropriately distanced infusion chairs in some already overburdened systems must be considered in this discussion. We agree with the ACR, whose infusion guidance recommends that “possible changes might include temporary interruption of therapy, temporary initiation of a bridge therapy such as a less potent anti-inflammatory or immune-modulating agent, or temporary change to an alternative therapy.”

We also reinforce recommended behaviors for preventing infection, including social distancing, frequent handwashing, and avoiding touching one’s face.

Patients with rheumatic disease and confirmed or suspected COVID-19 infection

With the worldwide spread of COVID-19, patients with rheumatic diseases will undoubtedly be among those exposed and infected. Though current data are limited, within a cohort from China, 1% had an autoimmune disease. Testing recommendations to confirm COVID-19 and decision guidelines for outpatient versus inpatient management are evolving, and we consult the most up-to-date, local information regarding testing as individual potential cases arise.

For patients who develop COVID-19 and are currently taking DMARDs and biologics, we recommend that they discontinue these medications, with the exception of hydroxychloroquine (HCQ). HCQ may be continued because its mechanism is not expected to worsen infection, and it plays a key role in the management of patients with systemic lupus erythematosus (SLE). In addition, in vitro antiviral effects have been reported and there is growing interest for its use in the management of COVID-19. However, there are conflicting data and methodological concerns about the nonrandomized human studies that suggest a benefit of HCQ against COVID-19.

The decision regarding management of glucocorticoids in the setting of new COVID-19 infection is challenging and should be individualized. At present, expert panels recommend against the use of glucocorticoids among individuals with COVID-19 who do not have acute respiratory distress syndrome. However, adrenal insufficiency must be considered among patients with COVID-19 who are treated with chronic glucocorticoids. Again, these decisions should be made on an individual, case-by-case basis.

Implications of a hydroxychloroquine shortage

The use of HCQ in rheumatology is supported by years of research. Particularly in SLE, HCQ has been shown to reduce disease activity and damage and to improve survival. Furthermore, for pregnant patients with SLE, numerous studies have demonstrated the safety and benefit of HCQ for both the mother and fetus; thus, it is strongly recommended. By contrast, despite the growing interest for HCQ in patients with COVID-19, the evidence is inconclusive and limited.

The ACR suggests that decisions regarding HCQ dose reductions to extend individual patients supplies should be tailored to each patient’s need and risk in the unfortunate setting of medication shortages. Even in patients with stable SLE, however, disease flares at 6 months are more common among individuals who discontinue HCQ. Of note, these flares may incorporate novel and severe disease manifestations.

Unfortunately, other therapeutic options for SLE are associated with more adverse effects (including increased susceptibility to infection) or are largely unavailable (e.g., quinacrine). Thus, we strive to continue standard dosing of HCQ for patients who are currently flaring or recently flared, and we make shared, individualized decisions for those patients with stable disease as the HCQ shortage evolves.

Future research on COVID-19 and rheumatic disease

While we might expect that an underlying rheumatic disease and associated treatments may predispose individuals to developing COVID-19, current data do not indicate which, if any, rheumatic diseases and associated therapies convey the greatest risk.

To address this uncertainty, the rheumatology community created the COVID-19 Global Rheumatology Alliance, an international effort to initiate and maintain a deidentified patient registry for individuals with rheumatic disease who develop COVID-19. These efforts will allow us to gain essential insights regarding which patient demographics, underlying diseases, and medications are most common among patients who develop COVID-19.

This alliance encourages rheumatologists and those caring for patients with rheumatic diseases to report their patient cases to this registry. As we are confronted with making management decisions with a scarcity of supporting data, efforts like these will improve our ability to make individualized treatment recommendations.

The COVID-19 pandemic has presented us all with unprecedented challenges. As rheumatologists, it is our duty to lead our patients through this uncharted territory with close communication, information, advocacy, and personalized treatment decisions. Each of these is central to the management of rheumatology patients during the COVID-19 pandemic.

With the growing interest in immunomodulatory therapies for the complications of this infection, we have the unique opportunity to share our expertise, recommendations, and caution with our colleagues. As clinicians and scientists, we must advocate for data collection and studies that will allow us to develop novel, data-driven disease management approaches while providing the best care possible for our patients.

Stephen Paget, MD, is physician in chief emeritus for the Center for Rheumatology at Hospital for Special Surgery in New York. Kimberly Showalter, MD, is a third-year rheumatology fellow at Hospital for Special Surgery. Sebastian E. Sattui, MD, is a third-year rheumatology and 1-year vasculitis fellow at Hospital for Special Surgery.

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

When COVID-19 is suspected or confirmed in a patient with a rheumatic disease, treatment with hydroxychloroquine may be continued, but other treatments may need to be stopped or held temporarily, according to new guidance issued by the American College of Rheumatology.

That includes disease-modifying treatment with antirheumatic drugs such as sulfasalazine, methotrexate, leflunomide, and the Janus kinase (JAK) inhibitors, as well as immunosuppressants and non-interleukin (IL)-6 biologics, and this is regardless of how severe the COVID-19 illness is. NSAIDs should also be stopped if there are respiratory symptoms.

The advice is slightly less drastic if someone with stable rheumatic disease has probably been exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or are asymptomatic. In those patients, DMARDs may be continued, although there is uncertainty over whether there is a need to temporarily stop methotrexate or leflunomide. Interruption of immunosuppressive, non–IL-6, and JAK inhibitor treatment is advised pending a negative SARS-CoV-2 test result, assuming the patient’s rheumatic disease is stable.
 

Impetus for ACR COVID-19 guidance

“One of the earliest challenges for rheumatologists during the COVID-19 pandemic was determining how to advise our patients who were taking immunosuppressive medications and were concerned as to whether or not to discontinue their therapy,” ACR President Ellen Gravallese, MD, said in an interview about the ACR Clinical Guidance Document, which is published online in Arthritis & Rheumatology.

“A second challenge was keeping our patients safe from exposure to the virus, while still seeing those patients in person who required office visits,” added Dr. Gravallese, who is chief of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital in Boston.

She continued: “The ACR Clinical Guidance Document was prepared in order to assist rheumatologists with decisions as to how to handle current medications during different phases of a patient’s exposure to the SARS-CoV-2 virus.”

But with very little evidence available on how to manage COVID-19 patients generally, let alone specifically in those with rheumatic diseases, “it became evident that any recommendations made would need to be done in a thoughtful and organized manner, evaluating the evidence that was available and obtaining the advice of experts in infectious disease, epidemiology, and in the use of biologic and nonbiologic agents for rheumatic disease,” she said.

As such, the ACR convened a task force of 10 rheumatologists and 4 infectious disease specialists from North America to look at how best to manage patients with rheumatic disease during the COVID-19 pandemic.

“Our charge was to develop a guidance document for the care of adult rheumatic disease patients in the context of COVID-19 and not per se to provide guidance for the treatment of COVID-19,” explained task force member and the corresponding author for the guidance, Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center, Omaha.

Dr. Mikuls, who was speaking at a virtual town hall meeting hosted by the ACR on May 6, noted that the guidance was obviously based on the best consensus of the available data and as such represented a “living document” that “would change and be added to” as necessary.
 

General recommendations for adult rheumatic disease management

In terms of general recommendations for the management of adult rheumatic disease patients, Dr. Mikuls said that six statements had been made “specific to risk assessment, prevention of infection, and best practices related to glucocorticoid use and the use of ACE [angiotensin-converting enzyme] inhibitors and ARBs [angiotensin II receptor blockers] during the pandemic.”

For example, general advice is to counsel patients to keep up general preventive measures such as social distancing and regular hand washing, reducing the number of in-person health care visits, and undertaking other means to try to prevent potential SARS-CoV-2 exposure. As for general treatment advice, glucocorticoids should be used at their lowest doses possible and should not be abruptly stopped, and antihypertensive treatment should be used as indicated.

Additional guidance statements include those that address the treatment of patients with stable rheumatic disease in the absence of infection or known exposure to SARS-CoV-2, with guidance specific to the treatment of systemic lupus erythematosus (SLE), and those with newly diagnosed or active rheumatic disease.
 

SLE and inflammatory arthritis recommendations

“There are several sections within the guidance document that address the treatment of patients with systemic lupus erythematosus during this pandemic,” Dr. Gravallese pointed out. “In general, it is recommended that lupus patients who are currently taking hydroxychloroquine can remain on the therapy prior to and during infection and that newly diagnosed patients with lupus can be placed on this medication at full dose. It is recommended that pregnant patients with lupus remain on therapy with this drug.”

She also observed that, for the treatment of active inflammatory arthritis, “the recommendations were written to address specific medications that could be used in this setting. In general, the task force recommendations were guided by the importance of controlling inflammation prior to exposure to the virus, even during this pandemic.
 

Guidance raises questions

During the ACR’s town hall meeting, the task force answered several questions raised by the guidance, such as the reasoning behind recommending that the use of traditional DMARDs be discontinued in patients with confirmed SARS-CoV-2 infection.

Dr. Mikuls observed: “Maybe if you just read the guidance statements it isn’t terribly intuitive.” There was a lot of discussion about whether or not conventional DMARDs were immunosuppressive, and even though they may not have such effects, it was decided to err on the side of caution.

“I think the task force felt that, with a COVID-19–positive patient, there is a concern of potentially confusing adverse effects related to medicines or conflate those with problems from the infection,” he said. Although rare, examples of those issues could be drug-induced hypersensitivity, hypersensitivity pneumonitis, or gastrointestinal side effects of hepatitis, all of which have been described in COVID-19. “Not only could it cause confusion, but it could maybe worsen those sequalae of COVID-19,” he said.

“I think the other part of this answer was that the panel really felt that the risk in terms of the flaring of the underlying rheumatic disease was likely to be pretty low given the finite time frame you’d be taking about – usually a time frame of 2-3 weeks you’d be holding the agent – so I think that is really why the task force ended up with that recommendation.”

Similarly, for the JAK inhibitors, the decision was to err on the side of caution when COVID-19 was suspected or confirmed. “Not so much because of the risk of thromboembolic disease, but concerns over immunosuppression that these drugs carry with them and also the fact the JAK inhibitors are probably inhibitors of type 1 interferons, which play a significant role in viral immunity and could potentially have a negative impact,” said Stanley Cohen, MD, who practices rheumatology in the Dallas area.

“On the flipside, there is interest in some of the JAK inhibitors as a potential treatment for COVID-19,” Dr. Cohen said, referring to anecdotal evidence for baricitinib (Olumiant).

Michael Weinblatt, MD, of Brigham and Women’s Hospital, addressed the recent concern over the use of NSAIDs by the public.

“There’s been a lot in the lay press that NSAIDs – because of the effects on receptors in the lung – could lead to deleterious outcomes in patients with COVID and there’s very little data to support this.

“We did recommend that NSAIDs be held in the hospitalized patient and that wasn’t because of the COVID-19 issue, it really was just medical practice, and we didn’t want to confound the care of these really sick patients with potential toxicities from NSAIDs. But as far as routine rheumatological care in your outpatients, we did not recommend that nonsteroidals be stopped if they were tolerated.”

One part of the guidance that might already need revision is the recommendation on the continued use of hydroxychloroquine in patients who develop COVID-19.

“Our guidance document says it’s OK; we were all in very strong agreement to continue hydroxychloroquine in our patients with COVID-19 because at that point, just a couple of weeks ago, we thought it was part of the potential treatment,” Karen Costenbader, MD, MPH, of Brigham and Women’s Hospital, said during the town hall meeting.

“Now the pendulum has swung the other way, and we’re worried about maybe we shouldn’t be continuing it because COVID-19 patients will be getting many other medications,” Dr. Costenbader said, and these may affect the QT-interval. “They will not be getting azithromycin because the pendulum swung the other way on that one too, but definitely on many other medications when they are sick.”

Potentially, she added, “if the rheumatic disease is under good control the inpatient physicians could decide whether they should continue [hydroxychloroquine] or not. If the COVID-19 is a mild disease, I would say we probably could continue in accordance with what we put in the document, but we will have to revisit this as well.”
 

Guidance is a ‘living document’

“We will be providing updates to the Clinical Guidance Document as the need arises,” Dr. Gravallese emphasized. While the general recommendations are unlikely to change very much, “the task force will be interested in seeing the results of all new data, but the results of randomized, clinical trials will be particularly important as they become available,” she said. In particular, randomized, controlled trials of glucocorticoids and IL-6 receptor blockade for use in COVID-19 will be of great importance.

“In this initial document, we could not take on all of the medical scenarios our members will face. For example, we could not take on recommendations for the pediatric population as this group of patients has a very different response than adults to the SARS-CoV-2 virus,” Dr. Gravallese acknowledged. The plan is to provide guidance for that group of patients soon.

In addition, the ACR Executive Committee has appointed a Practice and Advocacy Task Force that will “address issues rheumatologists face on the practice side, including advice regarding how to effectively use telemedicine, address the frequency and safety of infusions, determine urgent versus nonurgent issues that would or would not require face-to-face visits, and help with financial challenges.”

The American College of Rheumatology supported the guidance-development process. Dr. Mikuls, Dr. Weinblatt, Dr. Cohen, and Dr. Costenbader each disclosed research support or consultancies with multiple pharmaceutical companies. Dr. Gravallese had no disclosures.

SOURCE: Mikuls TR et al. Arthritis Rheumatol. 2020 Apr 29. doi: 10.1002/art.41301.

When COVID-19 is suspected or confirmed in a patient with a rheumatic disease, treatment with hydroxychloroquine may be continued, but other treatments may need to be stopped or held temporarily, according to new guidance issued by the American College of Rheumatology.

That includes disease-modifying treatment with antirheumatic drugs such as sulfasalazine, methotrexate, leflunomide, and the Janus kinase (JAK) inhibitors, as well as immunosuppressants and non-interleukin (IL)-6 biologics, and this is regardless of how severe the COVID-19 illness is. NSAIDs should also be stopped if there are respiratory symptoms.

The advice is slightly less drastic if someone with stable rheumatic disease has probably been exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or are asymptomatic. In those patients, DMARDs may be continued, although there is uncertainty over whether there is a need to temporarily stop methotrexate or leflunomide. Interruption of immunosuppressive, non–IL-6, and JAK inhibitor treatment is advised pending a negative SARS-CoV-2 test result, assuming the patient’s rheumatic disease is stable.
 

Impetus for ACR COVID-19 guidance

“One of the earliest challenges for rheumatologists during the COVID-19 pandemic was determining how to advise our patients who were taking immunosuppressive medications and were concerned as to whether or not to discontinue their therapy,” ACR President Ellen Gravallese, MD, said in an interview about the ACR Clinical Guidance Document, which is published online in Arthritis & Rheumatology.

“A second challenge was keeping our patients safe from exposure to the virus, while still seeing those patients in person who required office visits,” added Dr. Gravallese, who is chief of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital in Boston.

She continued: “The ACR Clinical Guidance Document was prepared in order to assist rheumatologists with decisions as to how to handle current medications during different phases of a patient’s exposure to the SARS-CoV-2 virus.”

But with very little evidence available on how to manage COVID-19 patients generally, let alone specifically in those with rheumatic diseases, “it became evident that any recommendations made would need to be done in a thoughtful and organized manner, evaluating the evidence that was available and obtaining the advice of experts in infectious disease, epidemiology, and in the use of biologic and nonbiologic agents for rheumatic disease,” she said.

As such, the ACR convened a task force of 10 rheumatologists and 4 infectious disease specialists from North America to look at how best to manage patients with rheumatic disease during the COVID-19 pandemic.

“Our charge was to develop a guidance document for the care of adult rheumatic disease patients in the context of COVID-19 and not per se to provide guidance for the treatment of COVID-19,” explained task force member and the corresponding author for the guidance, Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center, Omaha.

Dr. Mikuls, who was speaking at a virtual town hall meeting hosted by the ACR on May 6, noted that the guidance was obviously based on the best consensus of the available data and as such represented a “living document” that “would change and be added to” as necessary.
 

General recommendations for adult rheumatic disease management

In terms of general recommendations for the management of adult rheumatic disease patients, Dr. Mikuls said that six statements had been made “specific to risk assessment, prevention of infection, and best practices related to glucocorticoid use and the use of ACE [angiotensin-converting enzyme] inhibitors and ARBs [angiotensin II receptor blockers] during the pandemic.”

For example, general advice is to counsel patients to keep up general preventive measures such as social distancing and regular hand washing, reducing the number of in-person health care visits, and undertaking other means to try to prevent potential SARS-CoV-2 exposure. As for general treatment advice, glucocorticoids should be used at their lowest doses possible and should not be abruptly stopped, and antihypertensive treatment should be used as indicated.

Additional guidance statements include those that address the treatment of patients with stable rheumatic disease in the absence of infection or known exposure to SARS-CoV-2, with guidance specific to the treatment of systemic lupus erythematosus (SLE), and those with newly diagnosed or active rheumatic disease.
 

SLE and inflammatory arthritis recommendations

“There are several sections within the guidance document that address the treatment of patients with systemic lupus erythematosus during this pandemic,” Dr. Gravallese pointed out. “In general, it is recommended that lupus patients who are currently taking hydroxychloroquine can remain on the therapy prior to and during infection and that newly diagnosed patients with lupus can be placed on this medication at full dose. It is recommended that pregnant patients with lupus remain on therapy with this drug.”

She also observed that, for the treatment of active inflammatory arthritis, “the recommendations were written to address specific medications that could be used in this setting. In general, the task force recommendations were guided by the importance of controlling inflammation prior to exposure to the virus, even during this pandemic.
 

Guidance raises questions

During the ACR’s town hall meeting, the task force answered several questions raised by the guidance, such as the reasoning behind recommending that the use of traditional DMARDs be discontinued in patients with confirmed SARS-CoV-2 infection.

Dr. Mikuls observed: “Maybe if you just read the guidance statements it isn’t terribly intuitive.” There was a lot of discussion about whether or not conventional DMARDs were immunosuppressive, and even though they may not have such effects, it was decided to err on the side of caution.

“I think the task force felt that, with a COVID-19–positive patient, there is a concern of potentially confusing adverse effects related to medicines or conflate those with problems from the infection,” he said. Although rare, examples of those issues could be drug-induced hypersensitivity, hypersensitivity pneumonitis, or gastrointestinal side effects of hepatitis, all of which have been described in COVID-19. “Not only could it cause confusion, but it could maybe worsen those sequalae of COVID-19,” he said.

“I think the other part of this answer was that the panel really felt that the risk in terms of the flaring of the underlying rheumatic disease was likely to be pretty low given the finite time frame you’d be taking about – usually a time frame of 2-3 weeks you’d be holding the agent – so I think that is really why the task force ended up with that recommendation.”

Similarly, for the JAK inhibitors, the decision was to err on the side of caution when COVID-19 was suspected or confirmed. “Not so much because of the risk of thromboembolic disease, but concerns over immunosuppression that these drugs carry with them and also the fact the JAK inhibitors are probably inhibitors of type 1 interferons, which play a significant role in viral immunity and could potentially have a negative impact,” said Stanley Cohen, MD, who practices rheumatology in the Dallas area.

“On the flipside, there is interest in some of the JAK inhibitors as a potential treatment for COVID-19,” Dr. Cohen said, referring to anecdotal evidence for baricitinib (Olumiant).

Michael Weinblatt, MD, of Brigham and Women’s Hospital, addressed the recent concern over the use of NSAIDs by the public.

“There’s been a lot in the lay press that NSAIDs – because of the effects on receptors in the lung – could lead to deleterious outcomes in patients with COVID and there’s very little data to support this.

“We did recommend that NSAIDs be held in the hospitalized patient and that wasn’t because of the COVID-19 issue, it really was just medical practice, and we didn’t want to confound the care of these really sick patients with potential toxicities from NSAIDs. But as far as routine rheumatological care in your outpatients, we did not recommend that nonsteroidals be stopped if they were tolerated.”

One part of the guidance that might already need revision is the recommendation on the continued use of hydroxychloroquine in patients who develop COVID-19.

“Our guidance document says it’s OK; we were all in very strong agreement to continue hydroxychloroquine in our patients with COVID-19 because at that point, just a couple of weeks ago, we thought it was part of the potential treatment,” Karen Costenbader, MD, MPH, of Brigham and Women’s Hospital, said during the town hall meeting.

“Now the pendulum has swung the other way, and we’re worried about maybe we shouldn’t be continuing it because COVID-19 patients will be getting many other medications,” Dr. Costenbader said, and these may affect the QT-interval. “They will not be getting azithromycin because the pendulum swung the other way on that one too, but definitely on many other medications when they are sick.”

Potentially, she added, “if the rheumatic disease is under good control the inpatient physicians could decide whether they should continue [hydroxychloroquine] or not. If the COVID-19 is a mild disease, I would say we probably could continue in accordance with what we put in the document, but we will have to revisit this as well.”
 

Guidance is a ‘living document’

“We will be providing updates to the Clinical Guidance Document as the need arises,” Dr. Gravallese emphasized. While the general recommendations are unlikely to change very much, “the task force will be interested in seeing the results of all new data, but the results of randomized, clinical trials will be particularly important as they become available,” she said. In particular, randomized, controlled trials of glucocorticoids and IL-6 receptor blockade for use in COVID-19 will be of great importance.

“In this initial document, we could not take on all of the medical scenarios our members will face. For example, we could not take on recommendations for the pediatric population as this group of patients has a very different response than adults to the SARS-CoV-2 virus,” Dr. Gravallese acknowledged. The plan is to provide guidance for that group of patients soon.

In addition, the ACR Executive Committee has appointed a Practice and Advocacy Task Force that will “address issues rheumatologists face on the practice side, including advice regarding how to effectively use telemedicine, address the frequency and safety of infusions, determine urgent versus nonurgent issues that would or would not require face-to-face visits, and help with financial challenges.”

The American College of Rheumatology supported the guidance-development process. Dr. Mikuls, Dr. Weinblatt, Dr. Cohen, and Dr. Costenbader each disclosed research support or consultancies with multiple pharmaceutical companies. Dr. Gravallese had no disclosures.

SOURCE: Mikuls TR et al. Arthritis Rheumatol. 2020 Apr 29. doi: 10.1002/art.41301.

When COVID-19 is suspected or confirmed in a patient with a rheumatic disease, treatment with hydroxychloroquine may be continued, but other treatments may need to be stopped or held temporarily, according to new guidance issued by the American College of Rheumatology.

That includes disease-modifying treatment with antirheumatic drugs such as sulfasalazine, methotrexate, leflunomide, and the Janus kinase (JAK) inhibitors, as well as immunosuppressants and non-interleukin (IL)-6 biologics, and this is regardless of how severe the COVID-19 illness is. NSAIDs should also be stopped if there are respiratory symptoms.

The advice is slightly less drastic if someone with stable rheumatic disease has probably been exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or are asymptomatic. In those patients, DMARDs may be continued, although there is uncertainty over whether there is a need to temporarily stop methotrexate or leflunomide. Interruption of immunosuppressive, non–IL-6, and JAK inhibitor treatment is advised pending a negative SARS-CoV-2 test result, assuming the patient’s rheumatic disease is stable.
 

Impetus for ACR COVID-19 guidance

“One of the earliest challenges for rheumatologists during the COVID-19 pandemic was determining how to advise our patients who were taking immunosuppressive medications and were concerned as to whether or not to discontinue their therapy,” ACR President Ellen Gravallese, MD, said in an interview about the ACR Clinical Guidance Document, which is published online in Arthritis & Rheumatology.

“A second challenge was keeping our patients safe from exposure to the virus, while still seeing those patients in person who required office visits,” added Dr. Gravallese, who is chief of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital in Boston.

She continued: “The ACR Clinical Guidance Document was prepared in order to assist rheumatologists with decisions as to how to handle current medications during different phases of a patient’s exposure to the SARS-CoV-2 virus.”

But with very little evidence available on how to manage COVID-19 patients generally, let alone specifically in those with rheumatic diseases, “it became evident that any recommendations made would need to be done in a thoughtful and organized manner, evaluating the evidence that was available and obtaining the advice of experts in infectious disease, epidemiology, and in the use of biologic and nonbiologic agents for rheumatic disease,” she said.

As such, the ACR convened a task force of 10 rheumatologists and 4 infectious disease specialists from North America to look at how best to manage patients with rheumatic disease during the COVID-19 pandemic.

“Our charge was to develop a guidance document for the care of adult rheumatic disease patients in the context of COVID-19 and not per se to provide guidance for the treatment of COVID-19,” explained task force member and the corresponding author for the guidance, Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center, Omaha.

Dr. Mikuls, who was speaking at a virtual town hall meeting hosted by the ACR on May 6, noted that the guidance was obviously based on the best consensus of the available data and as such represented a “living document” that “would change and be added to” as necessary.
 

General recommendations for adult rheumatic disease management

In terms of general recommendations for the management of adult rheumatic disease patients, Dr. Mikuls said that six statements had been made “specific to risk assessment, prevention of infection, and best practices related to glucocorticoid use and the use of ACE [angiotensin-converting enzyme] inhibitors and ARBs [angiotensin II receptor blockers] during the pandemic.”

For example, general advice is to counsel patients to keep up general preventive measures such as social distancing and regular hand washing, reducing the number of in-person health care visits, and undertaking other means to try to prevent potential SARS-CoV-2 exposure. As for general treatment advice, glucocorticoids should be used at their lowest doses possible and should not be abruptly stopped, and antihypertensive treatment should be used as indicated.

Additional guidance statements include those that address the treatment of patients with stable rheumatic disease in the absence of infection or known exposure to SARS-CoV-2, with guidance specific to the treatment of systemic lupus erythematosus (SLE), and those with newly diagnosed or active rheumatic disease.
 

SLE and inflammatory arthritis recommendations

“There are several sections within the guidance document that address the treatment of patients with systemic lupus erythematosus during this pandemic,” Dr. Gravallese pointed out. “In general, it is recommended that lupus patients who are currently taking hydroxychloroquine can remain on the therapy prior to and during infection and that newly diagnosed patients with lupus can be placed on this medication at full dose. It is recommended that pregnant patients with lupus remain on therapy with this drug.”

She also observed that, for the treatment of active inflammatory arthritis, “the recommendations were written to address specific medications that could be used in this setting. In general, the task force recommendations were guided by the importance of controlling inflammation prior to exposure to the virus, even during this pandemic.
 

Guidance raises questions

During the ACR’s town hall meeting, the task force answered several questions raised by the guidance, such as the reasoning behind recommending that the use of traditional DMARDs be discontinued in patients with confirmed SARS-CoV-2 infection.

Dr. Mikuls observed: “Maybe if you just read the guidance statements it isn’t terribly intuitive.” There was a lot of discussion about whether or not conventional DMARDs were immunosuppressive, and even though they may not have such effects, it was decided to err on the side of caution.

“I think the task force felt that, with a COVID-19–positive patient, there is a concern of potentially confusing adverse effects related to medicines or conflate those with problems from the infection,” he said. Although rare, examples of those issues could be drug-induced hypersensitivity, hypersensitivity pneumonitis, or gastrointestinal side effects of hepatitis, all of which have been described in COVID-19. “Not only could it cause confusion, but it could maybe worsen those sequalae of COVID-19,” he said.

“I think the other part of this answer was that the panel really felt that the risk in terms of the flaring of the underlying rheumatic disease was likely to be pretty low given the finite time frame you’d be taking about – usually a time frame of 2-3 weeks you’d be holding the agent – so I think that is really why the task force ended up with that recommendation.”

Similarly, for the JAK inhibitors, the decision was to err on the side of caution when COVID-19 was suspected or confirmed. “Not so much because of the risk of thromboembolic disease, but concerns over immunosuppression that these drugs carry with them and also the fact the JAK inhibitors are probably inhibitors of type 1 interferons, which play a significant role in viral immunity and could potentially have a negative impact,” said Stanley Cohen, MD, who practices rheumatology in the Dallas area.

“On the flipside, there is interest in some of the JAK inhibitors as a potential treatment for COVID-19,” Dr. Cohen said, referring to anecdotal evidence for baricitinib (Olumiant).

Michael Weinblatt, MD, of Brigham and Women’s Hospital, addressed the recent concern over the use of NSAIDs by the public.

“There’s been a lot in the lay press that NSAIDs – because of the effects on receptors in the lung – could lead to deleterious outcomes in patients with COVID and there’s very little data to support this.

“We did recommend that NSAIDs be held in the hospitalized patient and that wasn’t because of the COVID-19 issue, it really was just medical practice, and we didn’t want to confound the care of these really sick patients with potential toxicities from NSAIDs. But as far as routine rheumatological care in your outpatients, we did not recommend that nonsteroidals be stopped if they were tolerated.”

One part of the guidance that might already need revision is the recommendation on the continued use of hydroxychloroquine in patients who develop COVID-19.

“Our guidance document says it’s OK; we were all in very strong agreement to continue hydroxychloroquine in our patients with COVID-19 because at that point, just a couple of weeks ago, we thought it was part of the potential treatment,” Karen Costenbader, MD, MPH, of Brigham and Women’s Hospital, said during the town hall meeting.

“Now the pendulum has swung the other way, and we’re worried about maybe we shouldn’t be continuing it because COVID-19 patients will be getting many other medications,” Dr. Costenbader said, and these may affect the QT-interval. “They will not be getting azithromycin because the pendulum swung the other way on that one too, but definitely on many other medications when they are sick.”

Potentially, she added, “if the rheumatic disease is under good control the inpatient physicians could decide whether they should continue [hydroxychloroquine] or not. If the COVID-19 is a mild disease, I would say we probably could continue in accordance with what we put in the document, but we will have to revisit this as well.”
 

Guidance is a ‘living document’

“We will be providing updates to the Clinical Guidance Document as the need arises,” Dr. Gravallese emphasized. While the general recommendations are unlikely to change very much, “the task force will be interested in seeing the results of all new data, but the results of randomized, clinical trials will be particularly important as they become available,” she said. In particular, randomized, controlled trials of glucocorticoids and IL-6 receptor blockade for use in COVID-19 will be of great importance.

“In this initial document, we could not take on all of the medical scenarios our members will face. For example, we could not take on recommendations for the pediatric population as this group of patients has a very different response than adults to the SARS-CoV-2 virus,” Dr. Gravallese acknowledged. The plan is to provide guidance for that group of patients soon.

In addition, the ACR Executive Committee has appointed a Practice and Advocacy Task Force that will “address issues rheumatologists face on the practice side, including advice regarding how to effectively use telemedicine, address the frequency and safety of infusions, determine urgent versus nonurgent issues that would or would not require face-to-face visits, and help with financial challenges.”

The American College of Rheumatology supported the guidance-development process. Dr. Mikuls, Dr. Weinblatt, Dr. Cohen, and Dr. Costenbader each disclosed research support or consultancies with multiple pharmaceutical companies. Dr. Gravallese had no disclosures.

SOURCE: Mikuls TR et al. Arthritis Rheumatol. 2020 Apr 29. doi: 10.1002/art.41301.

MAUI, HAWAII – Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

In addition to detailing the autoantibody red flags for ILD in juvenile dermatomyositis (JDM), she called for “hypervigilance” in patients with systemic juvenile idiopathic arthritis (SJIA) who exhibit any of a series of risk factors for ILD.

“Most of the lung disease in kids with systemic JIA is asymptomatic until very late, but it can be reversible if we treat it. So it’s worth finding and monitoring and giving everyone PCP [pneumocystis pneumonia] prophylaxis, because they have a high incidence of PCP if they have any of those risk factors,” observed Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
 

Autoantibodies predict ILD in JDM

Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 12% of 25 patients with juvenile polymyositis and in 18% of 44 youths with an overlap of juvenile connective tissue disease and myositis. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: Namely, 9% of the cohort were positive for antimelanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl tRNA synthestase (anti-Jo-1) autoantibodies were present in 4%.

A total of 33 of the 371 juvenile myositis patients had ILD based upon CT imaging, chest X-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo-1. After controlling for the presence of these other myositis-specific autoantibodies, auto-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.

Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52- and anti-Jo-1 positive.

Patients with anti-Ro52 autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
 

Novel potential treatment for ILD in JDM: JAK inhibitors

Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, intravenous immunoglobulin (IVIG), and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody-positive disease, according to Dr. Stevens.

For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody-positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near-resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.

Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals.

Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than did the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms.

The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.
 

Risk factors for ILD in SJIA

In the past half-dozen years or so, pediatric rheumatologists have become increasingly aware of and concerned about a new development in SJIA: the occurrence of comorbid ILD. This is a poor-prognosis disease: In a cohort from the United Kingdom, 5-year mortality from the time of diagnosis was 41%, fully 40-fold higher than in patients with SJIA only.

Patient cohorts with SJIA and ILD have unusual clinical and laboratory features that aren’t part of the typical picture in SJIA. These include acute clubbing, lymphopenia, a fixed pruritic rash, unexplained abdominal pain, peripheral eosinophilia, facial swelling, and an increased ferritin level, a hallmark of acute macrophage activation syndrome. Onset of SJIA before 2 years of age is another red flag associated with increased risk for ILD. So is trisomy 21, which is up to 50 times more prevalent in patients with SJIA and ILD than in the general population or in patients with SJIA only. Another clue is an adverse reaction to tocilizumab (Actemra).

Any of these findings warrant hypervigilance: “Be on high alert and monitor these patients for ILD much more closely,” Dr. Stevens advised.

This means ordering a CT scan, prescribing PCP prophylaxis, and regularly measuring pulmonary function, admittedly a challenge in children under 7 years old. In these younger kids, practical solutions include measuring their oxygen saturation before and after running around the room to see if it drops. A 6-minute walk test and sleep oximetry are other options.

The explanation for the abrupt arrival of ILD as part of the picture in SJIA during the past decade remains unclear. The timing coincides with a major advance in the treatment of SJIA: the arrival of biologic agents blocking interleukin-1 and -6. Could this be a serious treatment side effect?

“It’s all association so far, and we’re not really sure why we’re seeing this association. Is it because we’re using a lot [fewer] corticosteroids now, and maybe those were preventing lung disease in the past?” Dr. Stevens speculated.

At this point, she and her fellow pediatric rheumatologists are awaiting further evidence before discussing a curb in their use of IL-1 or -6 inhibitors in patients with SJIA.

“These drugs have turned around the lives of kids with SJIA. They used to suffer through all our ineffective treatments for years, with terrible joint destruction and a pretty high mortality rate. These are great drugs for this disease, and we certainly don’t want to limit them,” she said.

Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.

[email protected]

MAUI, HAWAII – Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

In addition to detailing the autoantibody red flags for ILD in juvenile dermatomyositis (JDM), she called for “hypervigilance” in patients with systemic juvenile idiopathic arthritis (SJIA) who exhibit any of a series of risk factors for ILD.

“Most of the lung disease in kids with systemic JIA is asymptomatic until very late, but it can be reversible if we treat it. So it’s worth finding and monitoring and giving everyone PCP [pneumocystis pneumonia] prophylaxis, because they have a high incidence of PCP if they have any of those risk factors,” observed Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
 

Autoantibodies predict ILD in JDM

Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 12% of 25 patients with juvenile polymyositis and in 18% of 44 youths with an overlap of juvenile connective tissue disease and myositis. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: Namely, 9% of the cohort were positive for antimelanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl tRNA synthestase (anti-Jo-1) autoantibodies were present in 4%.

A total of 33 of the 371 juvenile myositis patients had ILD based upon CT imaging, chest X-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo-1. After controlling for the presence of these other myositis-specific autoantibodies, auto-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.

Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52- and anti-Jo-1 positive.

Patients with anti-Ro52 autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
 

Novel potential treatment for ILD in JDM: JAK inhibitors

Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, intravenous immunoglobulin (IVIG), and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody-positive disease, according to Dr. Stevens.

For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody-positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near-resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.

Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals.

Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than did the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms.

The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.
 

Risk factors for ILD in SJIA

In the past half-dozen years or so, pediatric rheumatologists have become increasingly aware of and concerned about a new development in SJIA: the occurrence of comorbid ILD. This is a poor-prognosis disease: In a cohort from the United Kingdom, 5-year mortality from the time of diagnosis was 41%, fully 40-fold higher than in patients with SJIA only.

Patient cohorts with SJIA and ILD have unusual clinical and laboratory features that aren’t part of the typical picture in SJIA. These include acute clubbing, lymphopenia, a fixed pruritic rash, unexplained abdominal pain, peripheral eosinophilia, facial swelling, and an increased ferritin level, a hallmark of acute macrophage activation syndrome. Onset of SJIA before 2 years of age is another red flag associated with increased risk for ILD. So is trisomy 21, which is up to 50 times more prevalent in patients with SJIA and ILD than in the general population or in patients with SJIA only. Another clue is an adverse reaction to tocilizumab (Actemra).

Any of these findings warrant hypervigilance: “Be on high alert and monitor these patients for ILD much more closely,” Dr. Stevens advised.

This means ordering a CT scan, prescribing PCP prophylaxis, and regularly measuring pulmonary function, admittedly a challenge in children under 7 years old. In these younger kids, practical solutions include measuring their oxygen saturation before and after running around the room to see if it drops. A 6-minute walk test and sleep oximetry are other options.

The explanation for the abrupt arrival of ILD as part of the picture in SJIA during the past decade remains unclear. The timing coincides with a major advance in the treatment of SJIA: the arrival of biologic agents blocking interleukin-1 and -6. Could this be a serious treatment side effect?

“It’s all association so far, and we’re not really sure why we’re seeing this association. Is it because we’re using a lot [fewer] corticosteroids now, and maybe those were preventing lung disease in the past?” Dr. Stevens speculated.

At this point, she and her fellow pediatric rheumatologists are awaiting further evidence before discussing a curb in their use of IL-1 or -6 inhibitors in patients with SJIA.

“These drugs have turned around the lives of kids with SJIA. They used to suffer through all our ineffective treatments for years, with terrible joint destruction and a pretty high mortality rate. These are great drugs for this disease, and we certainly don’t want to limit them,” she said.

Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.

[email protected]

MAUI, HAWAII – Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

In addition to detailing the autoantibody red flags for ILD in juvenile dermatomyositis (JDM), she called for “hypervigilance” in patients with systemic juvenile idiopathic arthritis (SJIA) who exhibit any of a series of risk factors for ILD.

“Most of the lung disease in kids with systemic JIA is asymptomatic until very late, but it can be reversible if we treat it. So it’s worth finding and monitoring and giving everyone PCP [pneumocystis pneumonia] prophylaxis, because they have a high incidence of PCP if they have any of those risk factors,” observed Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
 

Autoantibodies predict ILD in JDM

Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 12% of 25 patients with juvenile polymyositis and in 18% of 44 youths with an overlap of juvenile connective tissue disease and myositis. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: Namely, 9% of the cohort were positive for antimelanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl tRNA synthestase (anti-Jo-1) autoantibodies were present in 4%.

A total of 33 of the 371 juvenile myositis patients had ILD based upon CT imaging, chest X-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo-1. After controlling for the presence of these other myositis-specific autoantibodies, auto-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.

Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52- and anti-Jo-1 positive.

Patients with anti-Ro52 autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
 

Novel potential treatment for ILD in JDM: JAK inhibitors

Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, intravenous immunoglobulin (IVIG), and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody-positive disease, according to Dr. Stevens.

For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody-positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near-resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.

Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals.

Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than did the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms.

The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.
 

Risk factors for ILD in SJIA

In the past half-dozen years or so, pediatric rheumatologists have become increasingly aware of and concerned about a new development in SJIA: the occurrence of comorbid ILD. This is a poor-prognosis disease: In a cohort from the United Kingdom, 5-year mortality from the time of diagnosis was 41%, fully 40-fold higher than in patients with SJIA only.

Patient cohorts with SJIA and ILD have unusual clinical and laboratory features that aren’t part of the typical picture in SJIA. These include acute clubbing, lymphopenia, a fixed pruritic rash, unexplained abdominal pain, peripheral eosinophilia, facial swelling, and an increased ferritin level, a hallmark of acute macrophage activation syndrome. Onset of SJIA before 2 years of age is another red flag associated with increased risk for ILD. So is trisomy 21, which is up to 50 times more prevalent in patients with SJIA and ILD than in the general population or in patients with SJIA only. Another clue is an adverse reaction to tocilizumab (Actemra).

Any of these findings warrant hypervigilance: “Be on high alert and monitor these patients for ILD much more closely,” Dr. Stevens advised.

This means ordering a CT scan, prescribing PCP prophylaxis, and regularly measuring pulmonary function, admittedly a challenge in children under 7 years old. In these younger kids, practical solutions include measuring their oxygen saturation before and after running around the room to see if it drops. A 6-minute walk test and sleep oximetry are other options.

The explanation for the abrupt arrival of ILD as part of the picture in SJIA during the past decade remains unclear. The timing coincides with a major advance in the treatment of SJIA: the arrival of biologic agents blocking interleukin-1 and -6. Could this be a serious treatment side effect?

“It’s all association so far, and we’re not really sure why we’re seeing this association. Is it because we’re using a lot [fewer] corticosteroids now, and maybe those were preventing lung disease in the past?” Dr. Stevens speculated.

At this point, she and her fellow pediatric rheumatologists are awaiting further evidence before discussing a curb in their use of IL-1 or -6 inhibitors in patients with SJIA.

“These drugs have turned around the lives of kids with SJIA. They used to suffer through all our ineffective treatments for years, with terrible joint destruction and a pretty high mortality rate. These are great drugs for this disease, and we certainly don’t want to limit them,” she said.

Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.

[email protected]

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

In the clinical opinion of Adam Friedman, MD, the emerging use of cannabinoids in dermatology is a trend that’s here to stay.

“There’s no question in my mind about that. Don’t play catch-up; be at the forefront, because at a minimum your patients are going to ask you about this,” he said in a video presentation during a virtual meeting held by the George Washington University department of dermatology.

In 2018, officials at Health Canada reviewed literature and international reviews concerning potential therapeutic uses and harmful effects of cannabis and cannabinoids and published a free downloadable guide for health care professionals. “In the book, dermatology doesn’t have its own section,” said Dr. Friedman, professor and interim chair of dermatology at George Washington University, Washington. “It falls under inflammation and makes up four paragraphs of the entire book, which is weird, given that if you survey the dispensaries in Canada, the majority of them led in with dermatologic indications, many of which are completely unsubstantiated.”

In the United States, a recent survey of 531 dermatologists led by Elizabeth S. Robinson, MD, of George Washington University, found that 55% reported at least one patient-initiated discussion about cannabinoids in the last year (J Drugs Dermatol. 2018;17[2]:1273-8). However, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most respondents (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. In an unpublished study conducted 2 years later, 155 dermatologists were asked if they had ever recommended medical cannabis products for the treatment/management of a dermatologic condition. More than 80% said they had not.

“It’s important to recognize that if we have a strong fund of knowledge, we can guide these patients to use the right cannabinoids for the right indications, so long as we have some evidence supporting it,” said Dr. Friedman, residency program director and director of translational research in George Washington University’s department of dermatology.

According to existing medical literature, cannabinoids may ultimately play a role in the treatment of eczema (J Am Acad Dermatol. 2020 May. doi: 10.1016/j.jaad.2020.01.036 and ClinicalTrials.gov NCT03824405), psoriasis, acne, and certain collagen vascular diseases, including scleroderma, dermatomyositis, and cutaneous lupus erythematosus (CLE). Most of the evidence for its use in collagen vascular diseases comes from the investigation of a synthetic cannabinoid known as anabasum, which is derived from TCH, but it has no affinity for the CB1 receptor. “Rather, it goes after the CB2 receptor, which is heavily prevalent in the immune system,” he noted.

In the summer of 2018, the FDA granted Orphan Drug Designation to Corbus Pharmaceuticals for lenabasum, a derivative of anabasum, for the treatment of dermatomyositis. “Hopefully, we’ll see this in the next year,” said Dr. Friedman, who consults for Corbus. A more recent study showed that lenabasum could reduce the production of interleukin-31 (Br. J Dermatol 2018;179[3]:669-78), which “I think will have broader implications in dermatology beyond dermatomyositis,” he said.

Dr. Friedman also reviewed data on a topical endocannabinoid nanoparticle-based formulation his team developed and is studying for the treatment of CLE. “There is a huge unmet need as there are no topical therapies approved for CLE,” he said. “Our animal data are very promising and we plan to move forward to human studies shortly.”

Resources for clinicians to improve their understanding about the potential use of cannabinoids in dermatology include an online certificate program in cannabis medicine offered by Thomas Jefferson University, as well as their state departments of health. Other resources include the International Cannabinoid Research Society, the International Association for Cannabinoid Medicines, the University of California’s Center for Medicinal Cannabis Research, and the Canadian Consortium for the Investigation of Cannabinoids.

Dr. Friedman noted that marijuana may exacerbate appetite, sleepiness, dizziness, low blood pressure, dry mouth/eyes, decreased urination, hallucinations, paranoia, anxiety, poor balance and posture in patients with dyskinetic disorders, and impaired attention, memory, and psychomotor performance. High concentrations can cause hyperemesis syndrome and exacerbate existing psychoses. With respect to cannabidiol (CBD), “unless you go with super high concentrations, over 50 mg/kg per day, you’re probably not going to run into so much trouble,” Dr. Friedman said. “Above that, you do get some liver function test abnormalities. The problem is, a lot of CBD-based products have impurities in them.”

Different state-based requirements exist for recommending cannabinoid products to your patients “so it’s important to know those requirements,” Dr. Friedman said. “I have patients sign a cannabis contrast. There are examples of these online. My mantra is start low and go slow, and stay low as much as possible.”

The virtual meeting at George Washington University included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Friedman reported that he serves as a consultant and/or adviser to numerous pharmaceutical companies, including some that produce cannabinoids. He is a speaker for Regeneron/Sanofi, Abbvie, and Dermira, and has received grants from Pfizer and the Dermatology Foundation.

[email protected]

In the clinical opinion of Adam Friedman, MD, the emerging use of cannabinoids in dermatology is a trend that’s here to stay.

“There’s no question in my mind about that. Don’t play catch-up; be at the forefront, because at a minimum your patients are going to ask you about this,” he said in a video presentation during a virtual meeting held by the George Washington University department of dermatology.

In 2018, officials at Health Canada reviewed literature and international reviews concerning potential therapeutic uses and harmful effects of cannabis and cannabinoids and published a free downloadable guide for health care professionals. “In the book, dermatology doesn’t have its own section,” said Dr. Friedman, professor and interim chair of dermatology at George Washington University, Washington. “It falls under inflammation and makes up four paragraphs of the entire book, which is weird, given that if you survey the dispensaries in Canada, the majority of them led in with dermatologic indications, many of which are completely unsubstantiated.”

In the United States, a recent survey of 531 dermatologists led by Elizabeth S. Robinson, MD, of George Washington University, found that 55% reported at least one patient-initiated discussion about cannabinoids in the last year (J Drugs Dermatol. 2018;17[2]:1273-8). However, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most respondents (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. In an unpublished study conducted 2 years later, 155 dermatologists were asked if they had ever recommended medical cannabis products for the treatment/management of a dermatologic condition. More than 80% said they had not.

“It’s important to recognize that if we have a strong fund of knowledge, we can guide these patients to use the right cannabinoids for the right indications, so long as we have some evidence supporting it,” said Dr. Friedman, residency program director and director of translational research in George Washington University’s department of dermatology.

According to existing medical literature, cannabinoids may ultimately play a role in the treatment of eczema (J Am Acad Dermatol. 2020 May. doi: 10.1016/j.jaad.2020.01.036 and ClinicalTrials.gov NCT03824405), psoriasis, acne, and certain collagen vascular diseases, including scleroderma, dermatomyositis, and cutaneous lupus erythematosus (CLE). Most of the evidence for its use in collagen vascular diseases comes from the investigation of a synthetic cannabinoid known as anabasum, which is derived from TCH, but it has no affinity for the CB1 receptor. “Rather, it goes after the CB2 receptor, which is heavily prevalent in the immune system,” he noted.

In the summer of 2018, the FDA granted Orphan Drug Designation to Corbus Pharmaceuticals for lenabasum, a derivative of anabasum, for the treatment of dermatomyositis. “Hopefully, we’ll see this in the next year,” said Dr. Friedman, who consults for Corbus. A more recent study showed that lenabasum could reduce the production of interleukin-31 (Br. J Dermatol 2018;179[3]:669-78), which “I think will have broader implications in dermatology beyond dermatomyositis,” he said.

Dr. Friedman also reviewed data on a topical endocannabinoid nanoparticle-based formulation his team developed and is studying for the treatment of CLE. “There is a huge unmet need as there are no topical therapies approved for CLE,” he said. “Our animal data are very promising and we plan to move forward to human studies shortly.”

Resources for clinicians to improve their understanding about the potential use of cannabinoids in dermatology include an online certificate program in cannabis medicine offered by Thomas Jefferson University, as well as their state departments of health. Other resources include the International Cannabinoid Research Society, the International Association for Cannabinoid Medicines, the University of California’s Center for Medicinal Cannabis Research, and the Canadian Consortium for the Investigation of Cannabinoids.

Dr. Friedman noted that marijuana may exacerbate appetite, sleepiness, dizziness, low blood pressure, dry mouth/eyes, decreased urination, hallucinations, paranoia, anxiety, poor balance and posture in patients with dyskinetic disorders, and impaired attention, memory, and psychomotor performance. High concentrations can cause hyperemesis syndrome and exacerbate existing psychoses. With respect to cannabidiol (CBD), “unless you go with super high concentrations, over 50 mg/kg per day, you’re probably not going to run into so much trouble,” Dr. Friedman said. “Above that, you do get some liver function test abnormalities. The problem is, a lot of CBD-based products have impurities in them.”

Different state-based requirements exist for recommending cannabinoid products to your patients “so it’s important to know those requirements,” Dr. Friedman said. “I have patients sign a cannabis contrast. There are examples of these online. My mantra is start low and go slow, and stay low as much as possible.”

The virtual meeting at George Washington University included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Friedman reported that he serves as a consultant and/or adviser to numerous pharmaceutical companies, including some that produce cannabinoids. He is a speaker for Regeneron/Sanofi, Abbvie, and Dermira, and has received grants from Pfizer and the Dermatology Foundation.

[email protected]

In the clinical opinion of Adam Friedman, MD, the emerging use of cannabinoids in dermatology is a trend that’s here to stay.

“There’s no question in my mind about that. Don’t play catch-up; be at the forefront, because at a minimum your patients are going to ask you about this,” he said in a video presentation during a virtual meeting held by the George Washington University department of dermatology.

In 2018, officials at Health Canada reviewed literature and international reviews concerning potential therapeutic uses and harmful effects of cannabis and cannabinoids and published a free downloadable guide for health care professionals. “In the book, dermatology doesn’t have its own section,” said Dr. Friedman, professor and interim chair of dermatology at George Washington University, Washington. “It falls under inflammation and makes up four paragraphs of the entire book, which is weird, given that if you survey the dispensaries in Canada, the majority of them led in with dermatologic indications, many of which are completely unsubstantiated.”

In the United States, a recent survey of 531 dermatologists led by Elizabeth S. Robinson, MD, of George Washington University, found that 55% reported at least one patient-initiated discussion about cannabinoids in the last year (J Drugs Dermatol. 2018;17[2]:1273-8). However, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most respondents (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. In an unpublished study conducted 2 years later, 155 dermatologists were asked if they had ever recommended medical cannabis products for the treatment/management of a dermatologic condition. More than 80% said they had not.

“It’s important to recognize that if we have a strong fund of knowledge, we can guide these patients to use the right cannabinoids for the right indications, so long as we have some evidence supporting it,” said Dr. Friedman, residency program director and director of translational research in George Washington University’s department of dermatology.

According to existing medical literature, cannabinoids may ultimately play a role in the treatment of eczema (J Am Acad Dermatol. 2020 May. doi: 10.1016/j.jaad.2020.01.036 and ClinicalTrials.gov NCT03824405), psoriasis, acne, and certain collagen vascular diseases, including scleroderma, dermatomyositis, and cutaneous lupus erythematosus (CLE). Most of the evidence for its use in collagen vascular diseases comes from the investigation of a synthetic cannabinoid known as anabasum, which is derived from TCH, but it has no affinity for the CB1 receptor. “Rather, it goes after the CB2 receptor, which is heavily prevalent in the immune system,” he noted.

In the summer of 2018, the FDA granted Orphan Drug Designation to Corbus Pharmaceuticals for lenabasum, a derivative of anabasum, for the treatment of dermatomyositis. “Hopefully, we’ll see this in the next year,” said Dr. Friedman, who consults for Corbus. A more recent study showed that lenabasum could reduce the production of interleukin-31 (Br. J Dermatol 2018;179[3]:669-78), which “I think will have broader implications in dermatology beyond dermatomyositis,” he said.

Dr. Friedman also reviewed data on a topical endocannabinoid nanoparticle-based formulation his team developed and is studying for the treatment of CLE. “There is a huge unmet need as there are no topical therapies approved for CLE,” he said. “Our animal data are very promising and we plan to move forward to human studies shortly.”

Resources for clinicians to improve their understanding about the potential use of cannabinoids in dermatology include an online certificate program in cannabis medicine offered by Thomas Jefferson University, as well as their state departments of health. Other resources include the International Cannabinoid Research Society, the International Association for Cannabinoid Medicines, the University of California’s Center for Medicinal Cannabis Research, and the Canadian Consortium for the Investigation of Cannabinoids.

Dr. Friedman noted that marijuana may exacerbate appetite, sleepiness, dizziness, low blood pressure, dry mouth/eyes, decreased urination, hallucinations, paranoia, anxiety, poor balance and posture in patients with dyskinetic disorders, and impaired attention, memory, and psychomotor performance. High concentrations can cause hyperemesis syndrome and exacerbate existing psychoses. With respect to cannabidiol (CBD), “unless you go with super high concentrations, over 50 mg/kg per day, you’re probably not going to run into so much trouble,” Dr. Friedman said. “Above that, you do get some liver function test abnormalities. The problem is, a lot of CBD-based products have impurities in them.”

Different state-based requirements exist for recommending cannabinoid products to your patients “so it’s important to know those requirements,” Dr. Friedman said. “I have patients sign a cannabis contrast. There are examples of these online. My mantra is start low and go slow, and stay low as much as possible.”

The virtual meeting at George Washington University included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Friedman reported that he serves as a consultant and/or adviser to numerous pharmaceutical companies, including some that produce cannabinoids. He is a speaker for Regeneron/Sanofi, Abbvie, and Dermira, and has received grants from Pfizer and the Dermatology Foundation.

[email protected]

Across the country, hospitals are incorporating Friday’s warning from the US Food and Drug Administration (FDA) about the risks of prescribing hydroxychloroquine and chloroquine for COVID-19 into their treatment protocols.

For some hospitals, the message affirmed the cautious approach they were already taking with hydroxychloroquine. “From a New York state or Northwell perspective, there is no major change,” said Onisis Stefas, PharmD, vice president of pharmacy at Northwell Health in New York. “We were not prescribing it out in the community very early on because of the concerns associated with the heart arrhythmias.”

Brigham and Women’s Hospital in Boston, Massachusetts, is currently in the process of updating its publicly available COVID-19 protocols website “to incorporate the FDA’s updated safety assessment and ongoing clinical trials,” a hospital spokesperson told Medscape Medical News. Prior to the updates, the treatment protocols indicated that hydroxychloroquine should only be considered after weighing the risks and benefits for patients who are not candidates for other clinical trials and meet a specific set of health criteria.

The warning is a timely and important synthesis of what physicians know about the drugs so far and how cautiously clinicians across the country should be using them, said Rajesh T. Gandhi, MD, infectious diseases physician at Massachusetts General Hospital (MGH), Boston, professor of medicine at Harvard Medical School, member of the Infectious Diseases Society of America (IDSA), and chair-elect of the HIV Medicine Association.

“I think to be honest it’s a really important message to the public and clinicians across the country,” said Gandhi. “Because we all know there is just a ton of discussion around this drug ... and it came out fairly and said what we know right now.”

The two antimalarial drugs have been at the center of much political debate and scientific scrutiny in recent weeks, following President Trump’s endorsement and the FDA’s emergency use authorization for the two medications in March. Hospitals across the country had incorporated hydroxychloroquine and chloroquine into their constantly evolving treatment protocols for patients with COVID-19.

But the evidence that these drugs actually help treat COVID-19 remains scant. Some small studies suggest the therapies help patients with COVID-19, while others conclude the drugs have no effect or even harm patients. In the United States, medical societies including the American Heart Association have also warned about the serious cardiac issues that can accompany these drugs for some patients.

In the new warning, the FDA said it “cautions against use of hydroxychloroquine or chloroquine for COVID-19 patients outside of the hospital setting or a clinical trial” and urged “close supervision” of patients treated with these therapies, citing cardiac side effects.

The FDA also said it is aware that the outpatient prescription of these medications has increased since its March authorization, but the drugs still have not been shown to be safe or effective in treating or preventing COVID-19.

The FDA announcement is consistent with protocols established by the National Institutes of Health and IDSA earlier this month that recommend against using hydroxychloroquine or chloroquine, except when these drugs are administered as part of a clinical trial.

“We agree wholeheartedly with the FDA and have been hoping that the FDA would in fact issue that kind of clarification,” said Samuel Brown, MD, study committee cochair of the ORCHID clinical trial, a multicenter, blinded study investigating the safety and efficacy of hydroxychloroquine. These medications need to be tested in clinical trials that are able to focus closely on safety monitoring, he said. Experts at Vanderbilt University, one of the medical centers participating in the ORCHID clinical trial, decided before Tennessee had any cases of COVID-19 that unproven therapies like hydroxychloroquine would only be available through clinical trials, said Wesley Self, MD, associate professor of emergency medicine at Vanderbilt University, Nashville, Tennessee, and chair of the ORCHID study committee.

Northwell Health, like other hospitals in New York, has been following a March executive order issued by Governor Andrew Cuomo limiting the use of these drugs for COVID-19 outside of clinical trials, said Stefas. At Northwell Health, patients with COVID-19 only receive hydroxychloroquine or chloroquine when treated in hospital, where they can be closely monitored, or as part of a clinical trial. The hospital system’s protocols currently do not recommend pairing hydroxychloroquine with azithromycin, said Stefas. The new FDA announcement is “very similar” to New York’s existing executive order, he said. “Reading through this reinforces a lot of what we originally thought.”

At MGH in Boston, the FDA safety warning is in line with and “solidifies” the hospital’s evolving protocols, said Gandhi. Clinicians at MGH have been steadily moving away from prescribing hydroxychloroquine outside of clinical trials as the efficacy has remained murky, the serious side effects have become more evident, and clinical trials to assess the drug have gotten underway in recent weeks, he said. Given the conflicting evidence, Gandhi feels the use of these drugs needs to be focused in clinical trials, where scientists can truly evaluate how much they help or harm.

“We know fundamentally that’s the way to do this,” Gandhi said. “We also don’t know that it doesn’t work, so it is ethical and incumbent upon us to do a study,” Gandhi said.

Other hospitals are already heeding the FDA’s warning. At UW Medicine in Washington state, for example, hydroxychloroquine was considered a possible treatment for COVID-19 prior to the FDA’s recent announcement. “Based on FDA guidance, hydroxychloroquine is no longer recommended as therapy for COVID-19 unless done through a clinical trial,” said Tim Dellit, MD, chief medical officer for UW Medicine.

Michigan Medicine stopped using hydroxychloroquine and azithromycin (both separately and in combination) about a month ago, said Daniel Kaul, MD, a professor of infectious disease at the University of Michigan. “When we reviewed the data that was available in more detail, we realized that it was essentially uninterpretable,” he said. As of Monday, the only patients receiving this drug at Michigan Medicine are those enrolled in the ORCHID clinical trial.

But that does not seem to be the case everywhere. Most patients transferred to Michigan Medicine from other hospitals have received these drugs, indicating they are still being widely used, said Kaul. “I think this FDA guidance is appropriate and may reduce usage of this drug and make people more aware of the potential side effects both in inpatient and outpatient settings.”

Hopefully, the FDA guidance will help slow the use of these drugs outside the appropriate clinical trial setting, said Kaul. “I think that the kind of politicization of this drug, which is pretty much unprecedented in my experience, created a really harmful environment where calm decision making and assessment of the relative risks and benefits became somewhat impossible,” said Kaul.

This article first appeared on Medscape.com.

Across the country, hospitals are incorporating Friday’s warning from the US Food and Drug Administration (FDA) about the risks of prescribing hydroxychloroquine and chloroquine for COVID-19 into their treatment protocols.

For some hospitals, the message affirmed the cautious approach they were already taking with hydroxychloroquine. “From a New York state or Northwell perspective, there is no major change,” said Onisis Stefas, PharmD, vice president of pharmacy at Northwell Health in New York. “We were not prescribing it out in the community very early on because of the concerns associated with the heart arrhythmias.”

Brigham and Women’s Hospital in Boston, Massachusetts, is currently in the process of updating its publicly available COVID-19 protocols website “to incorporate the FDA’s updated safety assessment and ongoing clinical trials,” a hospital spokesperson told Medscape Medical News. Prior to the updates, the treatment protocols indicated that hydroxychloroquine should only be considered after weighing the risks and benefits for patients who are not candidates for other clinical trials and meet a specific set of health criteria.

The warning is a timely and important synthesis of what physicians know about the drugs so far and how cautiously clinicians across the country should be using them, said Rajesh T. Gandhi, MD, infectious diseases physician at Massachusetts General Hospital (MGH), Boston, professor of medicine at Harvard Medical School, member of the Infectious Diseases Society of America (IDSA), and chair-elect of the HIV Medicine Association.

“I think to be honest it’s a really important message to the public and clinicians across the country,” said Gandhi. “Because we all know there is just a ton of discussion around this drug ... and it came out fairly and said what we know right now.”

The two antimalarial drugs have been at the center of much political debate and scientific scrutiny in recent weeks, following President Trump’s endorsement and the FDA’s emergency use authorization for the two medications in March. Hospitals across the country had incorporated hydroxychloroquine and chloroquine into their constantly evolving treatment protocols for patients with COVID-19.

But the evidence that these drugs actually help treat COVID-19 remains scant. Some small studies suggest the therapies help patients with COVID-19, while others conclude the drugs have no effect or even harm patients. In the United States, medical societies including the American Heart Association have also warned about the serious cardiac issues that can accompany these drugs for some patients.

In the new warning, the FDA said it “cautions against use of hydroxychloroquine or chloroquine for COVID-19 patients outside of the hospital setting or a clinical trial” and urged “close supervision” of patients treated with these therapies, citing cardiac side effects.

The FDA also said it is aware that the outpatient prescription of these medications has increased since its March authorization, but the drugs still have not been shown to be safe or effective in treating or preventing COVID-19.

The FDA announcement is consistent with protocols established by the National Institutes of Health and IDSA earlier this month that recommend against using hydroxychloroquine or chloroquine, except when these drugs are administered as part of a clinical trial.

“We agree wholeheartedly with the FDA and have been hoping that the FDA would in fact issue that kind of clarification,” said Samuel Brown, MD, study committee cochair of the ORCHID clinical trial, a multicenter, blinded study investigating the safety and efficacy of hydroxychloroquine. These medications need to be tested in clinical trials that are able to focus closely on safety monitoring, he said. Experts at Vanderbilt University, one of the medical centers participating in the ORCHID clinical trial, decided before Tennessee had any cases of COVID-19 that unproven therapies like hydroxychloroquine would only be available through clinical trials, said Wesley Self, MD, associate professor of emergency medicine at Vanderbilt University, Nashville, Tennessee, and chair of the ORCHID study committee.

Northwell Health, like other hospitals in New York, has been following a March executive order issued by Governor Andrew Cuomo limiting the use of these drugs for COVID-19 outside of clinical trials, said Stefas. At Northwell Health, patients with COVID-19 only receive hydroxychloroquine or chloroquine when treated in hospital, where they can be closely monitored, or as part of a clinical trial. The hospital system’s protocols currently do not recommend pairing hydroxychloroquine with azithromycin, said Stefas. The new FDA announcement is “very similar” to New York’s existing executive order, he said. “Reading through this reinforces a lot of what we originally thought.”

At MGH in Boston, the FDA safety warning is in line with and “solidifies” the hospital’s evolving protocols, said Gandhi. Clinicians at MGH have been steadily moving away from prescribing hydroxychloroquine outside of clinical trials as the efficacy has remained murky, the serious side effects have become more evident, and clinical trials to assess the drug have gotten underway in recent weeks, he said. Given the conflicting evidence, Gandhi feels the use of these drugs needs to be focused in clinical trials, where scientists can truly evaluate how much they help or harm.

“We know fundamentally that’s the way to do this,” Gandhi said. “We also don’t know that it doesn’t work, so it is ethical and incumbent upon us to do a study,” Gandhi said.

Other hospitals are already heeding the FDA’s warning. At UW Medicine in Washington state, for example, hydroxychloroquine was considered a possible treatment for COVID-19 prior to the FDA’s recent announcement. “Based on FDA guidance, hydroxychloroquine is no longer recommended as therapy for COVID-19 unless done through a clinical trial,” said Tim Dellit, MD, chief medical officer for UW Medicine.

Michigan Medicine stopped using hydroxychloroquine and azithromycin (both separately and in combination) about a month ago, said Daniel Kaul, MD, a professor of infectious disease at the University of Michigan. “When we reviewed the data that was available in more detail, we realized that it was essentially uninterpretable,” he said. As of Monday, the only patients receiving this drug at Michigan Medicine are those enrolled in the ORCHID clinical trial.

But that does not seem to be the case everywhere. Most patients transferred to Michigan Medicine from other hospitals have received these drugs, indicating they are still being widely used, said Kaul. “I think this FDA guidance is appropriate and may reduce usage of this drug and make people more aware of the potential side effects both in inpatient and outpatient settings.”

Hopefully, the FDA guidance will help slow the use of these drugs outside the appropriate clinical trial setting, said Kaul. “I think that the kind of politicization of this drug, which is pretty much unprecedented in my experience, created a really harmful environment where calm decision making and assessment of the relative risks and benefits became somewhat impossible,” said Kaul.

This article first appeared on Medscape.com.

Across the country, hospitals are incorporating Friday’s warning from the US Food and Drug Administration (FDA) about the risks of prescribing hydroxychloroquine and chloroquine for COVID-19 into their treatment protocols.

For some hospitals, the message affirmed the cautious approach they were already taking with hydroxychloroquine. “From a New York state or Northwell perspective, there is no major change,” said Onisis Stefas, PharmD, vice president of pharmacy at Northwell Health in New York. “We were not prescribing it out in the community very early on because of the concerns associated with the heart arrhythmias.”

Brigham and Women’s Hospital in Boston, Massachusetts, is currently in the process of updating its publicly available COVID-19 protocols website “to incorporate the FDA’s updated safety assessment and ongoing clinical trials,” a hospital spokesperson told Medscape Medical News. Prior to the updates, the treatment protocols indicated that hydroxychloroquine should only be considered after weighing the risks and benefits for patients who are not candidates for other clinical trials and meet a specific set of health criteria.

The warning is a timely and important synthesis of what physicians know about the drugs so far and how cautiously clinicians across the country should be using them, said Rajesh T. Gandhi, MD, infectious diseases physician at Massachusetts General Hospital (MGH), Boston, professor of medicine at Harvard Medical School, member of the Infectious Diseases Society of America (IDSA), and chair-elect of the HIV Medicine Association.

“I think to be honest it’s a really important message to the public and clinicians across the country,” said Gandhi. “Because we all know there is just a ton of discussion around this drug ... and it came out fairly and said what we know right now.”

The two antimalarial drugs have been at the center of much political debate and scientific scrutiny in recent weeks, following President Trump’s endorsement and the FDA’s emergency use authorization for the two medications in March. Hospitals across the country had incorporated hydroxychloroquine and chloroquine into their constantly evolving treatment protocols for patients with COVID-19.

But the evidence that these drugs actually help treat COVID-19 remains scant. Some small studies suggest the therapies help patients with COVID-19, while others conclude the drugs have no effect or even harm patients. In the United States, medical societies including the American Heart Association have also warned about the serious cardiac issues that can accompany these drugs for some patients.

In the new warning, the FDA said it “cautions against use of hydroxychloroquine or chloroquine for COVID-19 patients outside of the hospital setting or a clinical trial” and urged “close supervision” of patients treated with these therapies, citing cardiac side effects.

The FDA also said it is aware that the outpatient prescription of these medications has increased since its March authorization, but the drugs still have not been shown to be safe or effective in treating or preventing COVID-19.

The FDA announcement is consistent with protocols established by the National Institutes of Health and IDSA earlier this month that recommend against using hydroxychloroquine or chloroquine, except when these drugs are administered as part of a clinical trial.

“We agree wholeheartedly with the FDA and have been hoping that the FDA would in fact issue that kind of clarification,” said Samuel Brown, MD, study committee cochair of the ORCHID clinical trial, a multicenter, blinded study investigating the safety and efficacy of hydroxychloroquine. These medications need to be tested in clinical trials that are able to focus closely on safety monitoring, he said. Experts at Vanderbilt University, one of the medical centers participating in the ORCHID clinical trial, decided before Tennessee had any cases of COVID-19 that unproven therapies like hydroxychloroquine would only be available through clinical trials, said Wesley Self, MD, associate professor of emergency medicine at Vanderbilt University, Nashville, Tennessee, and chair of the ORCHID study committee.

Northwell Health, like other hospitals in New York, has been following a March executive order issued by Governor Andrew Cuomo limiting the use of these drugs for COVID-19 outside of clinical trials, said Stefas. At Northwell Health, patients with COVID-19 only receive hydroxychloroquine or chloroquine when treated in hospital, where they can be closely monitored, or as part of a clinical trial. The hospital system’s protocols currently do not recommend pairing hydroxychloroquine with azithromycin, said Stefas. The new FDA announcement is “very similar” to New York’s existing executive order, he said. “Reading through this reinforces a lot of what we originally thought.”

At MGH in Boston, the FDA safety warning is in line with and “solidifies” the hospital’s evolving protocols, said Gandhi. Clinicians at MGH have been steadily moving away from prescribing hydroxychloroquine outside of clinical trials as the efficacy has remained murky, the serious side effects have become more evident, and clinical trials to assess the drug have gotten underway in recent weeks, he said. Given the conflicting evidence, Gandhi feels the use of these drugs needs to be focused in clinical trials, where scientists can truly evaluate how much they help or harm.

“We know fundamentally that’s the way to do this,” Gandhi said. “We also don’t know that it doesn’t work, so it is ethical and incumbent upon us to do a study,” Gandhi said.

Other hospitals are already heeding the FDA’s warning. At UW Medicine in Washington state, for example, hydroxychloroquine was considered a possible treatment for COVID-19 prior to the FDA’s recent announcement. “Based on FDA guidance, hydroxychloroquine is no longer recommended as therapy for COVID-19 unless done through a clinical trial,” said Tim Dellit, MD, chief medical officer for UW Medicine.

Michigan Medicine stopped using hydroxychloroquine and azithromycin (both separately and in combination) about a month ago, said Daniel Kaul, MD, a professor of infectious disease at the University of Michigan. “When we reviewed the data that was available in more detail, we realized that it was essentially uninterpretable,” he said. As of Monday, the only patients receiving this drug at Michigan Medicine are those enrolled in the ORCHID clinical trial.

But that does not seem to be the case everywhere. Most patients transferred to Michigan Medicine from other hospitals have received these drugs, indicating they are still being widely used, said Kaul. “I think this FDA guidance is appropriate and may reduce usage of this drug and make people more aware of the potential side effects both in inpatient and outpatient settings.”

Hopefully, the FDA guidance will help slow the use of these drugs outside the appropriate clinical trial setting, said Kaul. “I think that the kind of politicization of this drug, which is pretty much unprecedented in my experience, created a really harmful environment where calm decision making and assessment of the relative risks and benefits became somewhat impossible,” said Kaul.

This article first appeared on Medscape.com.

The prevalence of dermatomyositis without dermatitis among patients with biopsy-confirmed dermatomyositis was approximately 8% in a Japanese cohort study. “Dermatomyositis sine dermatitis does exist and is significantly associated with anti–nuclear matrix protein 2 [anti-NXP-2] autoantibodies,” the researchers reported in JAMA Neurology.

Few case reports of dermatomyositis sine dermatitis have been documented. To confirm the existence of the condition, study its prevalence, and characterize its serologic features, Michio Inoue, MD, PhD, of the National Center of Neurology and Psychiatry in Tokyo, and colleagues conducted a cohort study of patients seen at the center between January 2009 and August 2019.

Of more than 8,800 patients whose muscle biopsies were examined for diagnostic purposes, 199 were tested for dermatomyositis-specific autoantibodies. The investigators excluded patients who did not have myxovirus resistance protein A expression in myofibers on muscle biopsy. In all, 182 patients with dermatomyositis were enrolled in the study (51% women; median age at biopsy, 56 years). Fourteen patients without a skin rash at the time of muscle biopsy received a diagnosis of dermatomyositis sine dermatitis. Before the muscle biopsy, most patients without a rash had a diagnosis of polymyositis.
 

Association with anti-NXP-2 autoantibodies

Anti-NXP-2 autoantibodies were detected in 86% of the patients without a rash at the time of biopsy, compared with 28% of the patients with rashes. “No other clinical or pathological characteristics were associated with [dermatomyositis sine dermatitis] except increased probability of developing perifascicular atrophy (71% vs. 43%),” Dr. Inoue and colleagues said.

During a median follow-up of 34 months, patients with dermatomyositis sine dermatitis received oral prednisolone with or without additional immunotherapy, and two patients had subcutaneous edema. Calcification was not seen during follow-up. “One patient with ... anti-NXP-2 autoantibodies had severe interstitial lung disease and needed noninvasive positive-pressure ventilation support,” the researchers said.

Four of the 14 patients with dermatomyositis sine dermatitis “developed skin rashes after muscle biopsy,” the researchers noted. “Similarly, a patient with [dermatomyositis sine dermatitis] was reported to have developed a skin rash 2 years after muscle biopsy.”

Potential therapies for refractory dermatomyositis, such as Janus kinase inhibitors, may not be effective for other types of myositis, so identifying patients with dermatomyositis may be “more essential than ever,” the authors said.
 

Effects on organ systems vary

The study is the first to systematically examine dermatomyositis sine dermatitis, said David Fiorentino, MD, PhD, professor of dermatology and director of the multidisciplinary rheumatic skin disease clinic at the Stanford (Calif.) University.

On the one hand, the results are not surprising because dermatomyositis is a systemic autoimmune disease. “There are no rules about which organs it will or won’t affect in a given individual,” Dr. Fiorentino said in an interview.

At the same time, dermatomyositis’s historical association with rash persists even though there is “no biological reason why that would have to be the case.”

Some patients with dermatomyositis have skin-predominant disease without clinically significant muscle involvement. Lung-predominant disease also may exist, although it has not been carefully studied, he said.

The findings remind clinicians that they need to consider the diagnosis of dermatomyositis “even if they do not have the skin findings,” he said. Dr. Fiorentino cautioned against interpreting the results to mean that certain patients never have signs of cutaneous inflammation. In the study, about a one-third of patients without dermatitis at the time of biopsy developed a rash. In addition, clinicians often miss subtle disease under the fingernails or on the scalp, or mild rash on the elbows.

The cohort of patients who underwent muscle biopsy may not be representative of the spectrum of patients with dermatomyositis, and the findings need to be verified in other populations, Dr. Fiorentino said.

The study was supported by an intramural research grant of the National Center of Neurology and Psychiatry and a grant from the Japan Society for the Promotion of Science. Authors disclosed personal fees from pharmaceutical companies and government and corporate grants outside the submitted work. Dr. Fiorentino had no relevant disclosures.

[email protected]

SOURCE: Inoue M et al. JAMA Neurol. 2020 Apr 20. doi: 10.1001/jamaneurol.2020.0673.

The prevalence of dermatomyositis without dermatitis among patients with biopsy-confirmed dermatomyositis was approximately 8% in a Japanese cohort study. “Dermatomyositis sine dermatitis does exist and is significantly associated with anti–nuclear matrix protein 2 [anti-NXP-2] autoantibodies,” the researchers reported in JAMA Neurology.

Few case reports of dermatomyositis sine dermatitis have been documented. To confirm the existence of the condition, study its prevalence, and characterize its serologic features, Michio Inoue, MD, PhD, of the National Center of Neurology and Psychiatry in Tokyo, and colleagues conducted a cohort study of patients seen at the center between January 2009 and August 2019.

Of more than 8,800 patients whose muscle biopsies were examined for diagnostic purposes, 199 were tested for dermatomyositis-specific autoantibodies. The investigators excluded patients who did not have myxovirus resistance protein A expression in myofibers on muscle biopsy. In all, 182 patients with dermatomyositis were enrolled in the study (51% women; median age at biopsy, 56 years). Fourteen patients without a skin rash at the time of muscle biopsy received a diagnosis of dermatomyositis sine dermatitis. Before the muscle biopsy, most patients without a rash had a diagnosis of polymyositis.
 

Association with anti-NXP-2 autoantibodies

Anti-NXP-2 autoantibodies were detected in 86% of the patients without a rash at the time of biopsy, compared with 28% of the patients with rashes. “No other clinical or pathological characteristics were associated with [dermatomyositis sine dermatitis] except increased probability of developing perifascicular atrophy (71% vs. 43%),” Dr. Inoue and colleagues said.

During a median follow-up of 34 months, patients with dermatomyositis sine dermatitis received oral prednisolone with or without additional immunotherapy, and two patients had subcutaneous edema. Calcification was not seen during follow-up. “One patient with ... anti-NXP-2 autoantibodies had severe interstitial lung disease and needed noninvasive positive-pressure ventilation support,” the researchers said.

Four of the 14 patients with dermatomyositis sine dermatitis “developed skin rashes after muscle biopsy,” the researchers noted. “Similarly, a patient with [dermatomyositis sine dermatitis] was reported to have developed a skin rash 2 years after muscle biopsy.”

Potential therapies for refractory dermatomyositis, such as Janus kinase inhibitors, may not be effective for other types of myositis, so identifying patients with dermatomyositis may be “more essential than ever,” the authors said.
 

Effects on organ systems vary

The study is the first to systematically examine dermatomyositis sine dermatitis, said David Fiorentino, MD, PhD, professor of dermatology and director of the multidisciplinary rheumatic skin disease clinic at the Stanford (Calif.) University.

On the one hand, the results are not surprising because dermatomyositis is a systemic autoimmune disease. “There are no rules about which organs it will or won’t affect in a given individual,” Dr. Fiorentino said in an interview.

At the same time, dermatomyositis’s historical association with rash persists even though there is “no biological reason why that would have to be the case.”

Some patients with dermatomyositis have skin-predominant disease without clinically significant muscle involvement. Lung-predominant disease also may exist, although it has not been carefully studied, he said.

The findings remind clinicians that they need to consider the diagnosis of dermatomyositis “even if they do not have the skin findings,” he said. Dr. Fiorentino cautioned against interpreting the results to mean that certain patients never have signs of cutaneous inflammation. In the study, about a one-third of patients without dermatitis at the time of biopsy developed a rash. In addition, clinicians often miss subtle disease under the fingernails or on the scalp, or mild rash on the elbows.

The cohort of patients who underwent muscle biopsy may not be representative of the spectrum of patients with dermatomyositis, and the findings need to be verified in other populations, Dr. Fiorentino said.

The study was supported by an intramural research grant of the National Center of Neurology and Psychiatry and a grant from the Japan Society for the Promotion of Science. Authors disclosed personal fees from pharmaceutical companies and government and corporate grants outside the submitted work. Dr. Fiorentino had no relevant disclosures.

[email protected]

SOURCE: Inoue M et al. JAMA Neurol. 2020 Apr 20. doi: 10.1001/jamaneurol.2020.0673.

The prevalence of dermatomyositis without dermatitis among patients with biopsy-confirmed dermatomyositis was approximately 8% in a Japanese cohort study. “Dermatomyositis sine dermatitis does exist and is significantly associated with anti–nuclear matrix protein 2 [anti-NXP-2] autoantibodies,” the researchers reported in JAMA Neurology.

Few case reports of dermatomyositis sine dermatitis have been documented. To confirm the existence of the condition, study its prevalence, and characterize its serologic features, Michio Inoue, MD, PhD, of the National Center of Neurology and Psychiatry in Tokyo, and colleagues conducted a cohort study of patients seen at the center between January 2009 and August 2019.

Of more than 8,800 patients whose muscle biopsies were examined for diagnostic purposes, 199 were tested for dermatomyositis-specific autoantibodies. The investigators excluded patients who did not have myxovirus resistance protein A expression in myofibers on muscle biopsy. In all, 182 patients with dermatomyositis were enrolled in the study (51% women; median age at biopsy, 56 years). Fourteen patients without a skin rash at the time of muscle biopsy received a diagnosis of dermatomyositis sine dermatitis. Before the muscle biopsy, most patients without a rash had a diagnosis of polymyositis.
 

Association with anti-NXP-2 autoantibodies

Anti-NXP-2 autoantibodies were detected in 86% of the patients without a rash at the time of biopsy, compared with 28% of the patients with rashes. “No other clinical or pathological characteristics were associated with [dermatomyositis sine dermatitis] except increased probability of developing perifascicular atrophy (71% vs. 43%),” Dr. Inoue and colleagues said.

During a median follow-up of 34 months, patients with dermatomyositis sine dermatitis received oral prednisolone with or without additional immunotherapy, and two patients had subcutaneous edema. Calcification was not seen during follow-up. “One patient with ... anti-NXP-2 autoantibodies had severe interstitial lung disease and needed noninvasive positive-pressure ventilation support,” the researchers said.

Four of the 14 patients with dermatomyositis sine dermatitis “developed skin rashes after muscle biopsy,” the researchers noted. “Similarly, a patient with [dermatomyositis sine dermatitis] was reported to have developed a skin rash 2 years after muscle biopsy.”

Potential therapies for refractory dermatomyositis, such as Janus kinase inhibitors, may not be effective for other types of myositis, so identifying patients with dermatomyositis may be “more essential than ever,” the authors said.
 

Effects on organ systems vary

The study is the first to systematically examine dermatomyositis sine dermatitis, said David Fiorentino, MD, PhD, professor of dermatology and director of the multidisciplinary rheumatic skin disease clinic at the Stanford (Calif.) University.

On the one hand, the results are not surprising because dermatomyositis is a systemic autoimmune disease. “There are no rules about which organs it will or won’t affect in a given individual,” Dr. Fiorentino said in an interview.

At the same time, dermatomyositis’s historical association with rash persists even though there is “no biological reason why that would have to be the case.”

Some patients with dermatomyositis have skin-predominant disease without clinically significant muscle involvement. Lung-predominant disease also may exist, although it has not been carefully studied, he said.

The findings remind clinicians that they need to consider the diagnosis of dermatomyositis “even if they do not have the skin findings,” he said. Dr. Fiorentino cautioned against interpreting the results to mean that certain patients never have signs of cutaneous inflammation. In the study, about a one-third of patients without dermatitis at the time of biopsy developed a rash. In addition, clinicians often miss subtle disease under the fingernails or on the scalp, or mild rash on the elbows.

The cohort of patients who underwent muscle biopsy may not be representative of the spectrum of patients with dermatomyositis, and the findings need to be verified in other populations, Dr. Fiorentino said.

The study was supported by an intramural research grant of the National Center of Neurology and Psychiatry and a grant from the Japan Society for the Promotion of Science. Authors disclosed personal fees from pharmaceutical companies and government and corporate grants outside the submitted work. Dr. Fiorentino had no relevant disclosures.

[email protected]

SOURCE: Inoue M et al. JAMA Neurol. 2020 Apr 20. doi: 10.1001/jamaneurol.2020.0673.