Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA) have an elevated risk of interstitial lung disease (ILD), but methotrexate does not accentuate that risk and may in fact be protective, new data show. These were among key findings of a pair of studies reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Although a guideline-recommended cornerstone in the management of RA, methotrexate has been associated with both hypersensitivity pneumonitis and diffuse lung disease. However, its involvement in the development of ILD among patients with RA is unclear.

A Danish study of more than 30,000 RA patients reported at the congress found that their risk of ILD was about three to five times that of the general population. However, risk did not differ significantly whether they had filled a methotrexate prescription or not.

In addition, a multinational case-control study of more than 1,000 RA patients also reported at the congress found that, compared with never-users of methotrexate, ever-users actually had a 59% lower likelihood of developing ILD.

However, both studies were limited by their retrospective design, Elizabeth R. Volkmann, MD, codirector of the connective tissue disease–related interstitial lung disease program at the University of California, Los Angeles, cautioned in an interview. Hence, there was likely systematic bias and confounding.

“I would interpret the conclusions of both studies with caution,” she maintained. “To understand how a particular intervention, such as methotrexate use, affects the outcome of ILD development, a prospective design is needed, which adequately adjusts for known ILD risk factors, such as male sex and smoking.”

As to whether the new findings are practice changing and how they might affect patient counseling, “the answers to these questions are not straightforward and depend on other patient-related factors,” according to Dr. Volkmann.
 

Danish nationwide study

René Cordtz, MD, a clinical assistant at the Center for Rheumatology and Spine Diseases, Rigshospitalet‐Gentofte, Copenhagen, and colleagues conducted a nationwide population-based cohort study using registry data from 1997 to 2015 to assess lung disease among patients with RA by prescriptions filled.

Results based on 30,512 RA patients showed that, compared with peers filling no methotrexate prescriptions, patients filling at least one did not have a significantly elevated risk of ILD at either 1 year of follow-up (hazard ratio, 1.03) or 5 years of follow-up (HR, 1.00). (Findings were similar for sulfasalazine, with respective nonsignificant HRs of 0.88 and 1.14.)

In addition, patients with RA had a similarly sharply elevated 5-year risk of ILD relative to the general population regardless of whether they had filled neither methotrexate nor sulfasalazine prescriptions (standardized incidence ratio, 3.38) or had filled prescriptions for methotrexate only (SIR, 3.63), sulfasalazine only (SIR, 4.12), or both (SIR, 5.45).

“RA patients have an increased risk of ILD, compared to the general population, which was not surprising, but very importantly, that risk was not further exacerbated in those treated with methotrexate,” Dr. Cordtz concluded. “We do acknowledge that purchasing your medicine is different from taking your medicine, which is why we found it extra reassuring that when requiring at least two methotrexate prescriptions to be considered exposed, it did not change our results.”

Multinational study

Pierre-Antoine Juge, MD, a rheumatologist at Bichat-Claude Bernard Hospital, Paris, and colleagues performed a case-control study among 482 RA patients with ILD and 741 RA patients without ILD in three cohorts: a French discovery cohort, a multinational (Brazilian, Italian, Mexican, United Kingdom, and United States) replication cohort, and a combined cohort. Those with methotrexate hypersensitivity pneumonitis were excluded.

Results showed that relative to peers without ILD, patients with ILD had a lower prevalence of ever having used methotrexate and had received a lower cumulative methotrexate dose, findings that were consistent across all three cohorts.

Methotrexate ever-use was associated with a significantly lower adjusted likelihood of ILD in the discovery cohort (odds ratio, 0.46), the replication cohort (OR, 0.38), and the combined cohort (OR, 0.41). Furthermore, ever-users were less commonly represented among patients with ILD regardless of chest high-resolution CT pattern (usual interstitial pneumonia pattern vs. not).

Finally, methotrexate use appeared to delay the adjusted time to onset of ILD by 3.5 years in the discovery cohort (P = .001), by 3.2 years in the replication cohort (P < .0001), and by 3.5 years in the combined cohort (P < .0001).

“Outside of methotrexate hypersensitivity pneumonitis, methotrexate was not a risk factor for RA-associated ILD in our study. We observed an inverse relationship that was similar whatever the high-resolution CT pattern,” Dr. Juge commented. “But this possible protective effect should be confirmed through a dedicated prospective, randomized, controlled trial.”

“Methotrexate should not be considered as a causal factor for RA-associated ILD, and its [discontinuation] should be discussed through a multidisciplinary discussion,” he recommended. In addition, “this study does not investigate the impact of methotrexate use on RA-associated ILD prognosis.”

The Danish study did not receive any specific funding, and none of its authors reported having any financial disclosures. The multinational study did not receive any specific funding. Dr. Juge disclosed that he had no relevant conflicts of interest, but many of his coauthors reported financial relationships with industry. Dr. Volkmann disclosed consulting for Boehringer Ingelheim and Forbius, and receiving grant support from Forbius and Corbus.

SOURCES: Cordtz R et al. Ann Rheum Dis. 2020;79[suppl 1]:147-8, Abstract OP0232; Juge P-A et al. Ann Rheum Dis. 2020;79[suppl 1]:25, Abstract OP0236.

Patients with rheumatoid arthritis (RA) have an elevated risk of interstitial lung disease (ILD), but methotrexate does not accentuate that risk and may in fact be protective, new data show. These were among key findings of a pair of studies reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Although a guideline-recommended cornerstone in the management of RA, methotrexate has been associated with both hypersensitivity pneumonitis and diffuse lung disease. However, its involvement in the development of ILD among patients with RA is unclear.

A Danish study of more than 30,000 RA patients reported at the congress found that their risk of ILD was about three to five times that of the general population. However, risk did not differ significantly whether they had filled a methotrexate prescription or not.

In addition, a multinational case-control study of more than 1,000 RA patients also reported at the congress found that, compared with never-users of methotrexate, ever-users actually had a 59% lower likelihood of developing ILD.

However, both studies were limited by their retrospective design, Elizabeth R. Volkmann, MD, codirector of the connective tissue disease–related interstitial lung disease program at the University of California, Los Angeles, cautioned in an interview. Hence, there was likely systematic bias and confounding.

“I would interpret the conclusions of both studies with caution,” she maintained. “To understand how a particular intervention, such as methotrexate use, affects the outcome of ILD development, a prospective design is needed, which adequately adjusts for known ILD risk factors, such as male sex and smoking.”

As to whether the new findings are practice changing and how they might affect patient counseling, “the answers to these questions are not straightforward and depend on other patient-related factors,” according to Dr. Volkmann.
 

Danish nationwide study

René Cordtz, MD, a clinical assistant at the Center for Rheumatology and Spine Diseases, Rigshospitalet‐Gentofte, Copenhagen, and colleagues conducted a nationwide population-based cohort study using registry data from 1997 to 2015 to assess lung disease among patients with RA by prescriptions filled.

Results based on 30,512 RA patients showed that, compared with peers filling no methotrexate prescriptions, patients filling at least one did not have a significantly elevated risk of ILD at either 1 year of follow-up (hazard ratio, 1.03) or 5 years of follow-up (HR, 1.00). (Findings were similar for sulfasalazine, with respective nonsignificant HRs of 0.88 and 1.14.)

In addition, patients with RA had a similarly sharply elevated 5-year risk of ILD relative to the general population regardless of whether they had filled neither methotrexate nor sulfasalazine prescriptions (standardized incidence ratio, 3.38) or had filled prescriptions for methotrexate only (SIR, 3.63), sulfasalazine only (SIR, 4.12), or both (SIR, 5.45).

“RA patients have an increased risk of ILD, compared to the general population, which was not surprising, but very importantly, that risk was not further exacerbated in those treated with methotrexate,” Dr. Cordtz concluded. “We do acknowledge that purchasing your medicine is different from taking your medicine, which is why we found it extra reassuring that when requiring at least two methotrexate prescriptions to be considered exposed, it did not change our results.”

Multinational study

Pierre-Antoine Juge, MD, a rheumatologist at Bichat-Claude Bernard Hospital, Paris, and colleagues performed a case-control study among 482 RA patients with ILD and 741 RA patients without ILD in three cohorts: a French discovery cohort, a multinational (Brazilian, Italian, Mexican, United Kingdom, and United States) replication cohort, and a combined cohort. Those with methotrexate hypersensitivity pneumonitis were excluded.

Results showed that relative to peers without ILD, patients with ILD had a lower prevalence of ever having used methotrexate and had received a lower cumulative methotrexate dose, findings that were consistent across all three cohorts.

Methotrexate ever-use was associated with a significantly lower adjusted likelihood of ILD in the discovery cohort (odds ratio, 0.46), the replication cohort (OR, 0.38), and the combined cohort (OR, 0.41). Furthermore, ever-users were less commonly represented among patients with ILD regardless of chest high-resolution CT pattern (usual interstitial pneumonia pattern vs. not).

Finally, methotrexate use appeared to delay the adjusted time to onset of ILD by 3.5 years in the discovery cohort (P = .001), by 3.2 years in the replication cohort (P < .0001), and by 3.5 years in the combined cohort (P < .0001).

“Outside of methotrexate hypersensitivity pneumonitis, methotrexate was not a risk factor for RA-associated ILD in our study. We observed an inverse relationship that was similar whatever the high-resolution CT pattern,” Dr. Juge commented. “But this possible protective effect should be confirmed through a dedicated prospective, randomized, controlled trial.”

“Methotrexate should not be considered as a causal factor for RA-associated ILD, and its [discontinuation] should be discussed through a multidisciplinary discussion,” he recommended. In addition, “this study does not investigate the impact of methotrexate use on RA-associated ILD prognosis.”

The Danish study did not receive any specific funding, and none of its authors reported having any financial disclosures. The multinational study did not receive any specific funding. Dr. Juge disclosed that he had no relevant conflicts of interest, but many of his coauthors reported financial relationships with industry. Dr. Volkmann disclosed consulting for Boehringer Ingelheim and Forbius, and receiving grant support from Forbius and Corbus.

SOURCES: Cordtz R et al. Ann Rheum Dis. 2020;79[suppl 1]:147-8, Abstract OP0232; Juge P-A et al. Ann Rheum Dis. 2020;79[suppl 1]:25, Abstract OP0236.

Patients with rheumatoid arthritis (RA) have an elevated risk of interstitial lung disease (ILD), but methotrexate does not accentuate that risk and may in fact be protective, new data show. These were among key findings of a pair of studies reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Although a guideline-recommended cornerstone in the management of RA, methotrexate has been associated with both hypersensitivity pneumonitis and diffuse lung disease. However, its involvement in the development of ILD among patients with RA is unclear.

A Danish study of more than 30,000 RA patients reported at the congress found that their risk of ILD was about three to five times that of the general population. However, risk did not differ significantly whether they had filled a methotrexate prescription or not.

In addition, a multinational case-control study of more than 1,000 RA patients also reported at the congress found that, compared with never-users of methotrexate, ever-users actually had a 59% lower likelihood of developing ILD.

However, both studies were limited by their retrospective design, Elizabeth R. Volkmann, MD, codirector of the connective tissue disease–related interstitial lung disease program at the University of California, Los Angeles, cautioned in an interview. Hence, there was likely systematic bias and confounding.

“I would interpret the conclusions of both studies with caution,” she maintained. “To understand how a particular intervention, such as methotrexate use, affects the outcome of ILD development, a prospective design is needed, which adequately adjusts for known ILD risk factors, such as male sex and smoking.”

As to whether the new findings are practice changing and how they might affect patient counseling, “the answers to these questions are not straightforward and depend on other patient-related factors,” according to Dr. Volkmann.
 

Danish nationwide study

René Cordtz, MD, a clinical assistant at the Center for Rheumatology and Spine Diseases, Rigshospitalet‐Gentofte, Copenhagen, and colleagues conducted a nationwide population-based cohort study using registry data from 1997 to 2015 to assess lung disease among patients with RA by prescriptions filled.

Results based on 30,512 RA patients showed that, compared with peers filling no methotrexate prescriptions, patients filling at least one did not have a significantly elevated risk of ILD at either 1 year of follow-up (hazard ratio, 1.03) or 5 years of follow-up (HR, 1.00). (Findings were similar for sulfasalazine, with respective nonsignificant HRs of 0.88 and 1.14.)

In addition, patients with RA had a similarly sharply elevated 5-year risk of ILD relative to the general population regardless of whether they had filled neither methotrexate nor sulfasalazine prescriptions (standardized incidence ratio, 3.38) or had filled prescriptions for methotrexate only (SIR, 3.63), sulfasalazine only (SIR, 4.12), or both (SIR, 5.45).

“RA patients have an increased risk of ILD, compared to the general population, which was not surprising, but very importantly, that risk was not further exacerbated in those treated with methotrexate,” Dr. Cordtz concluded. “We do acknowledge that purchasing your medicine is different from taking your medicine, which is why we found it extra reassuring that when requiring at least two methotrexate prescriptions to be considered exposed, it did not change our results.”

Multinational study

Pierre-Antoine Juge, MD, a rheumatologist at Bichat-Claude Bernard Hospital, Paris, and colleagues performed a case-control study among 482 RA patients with ILD and 741 RA patients without ILD in three cohorts: a French discovery cohort, a multinational (Brazilian, Italian, Mexican, United Kingdom, and United States) replication cohort, and a combined cohort. Those with methotrexate hypersensitivity pneumonitis were excluded.

Results showed that relative to peers without ILD, patients with ILD had a lower prevalence of ever having used methotrexate and had received a lower cumulative methotrexate dose, findings that were consistent across all three cohorts.

Methotrexate ever-use was associated with a significantly lower adjusted likelihood of ILD in the discovery cohort (odds ratio, 0.46), the replication cohort (OR, 0.38), and the combined cohort (OR, 0.41). Furthermore, ever-users were less commonly represented among patients with ILD regardless of chest high-resolution CT pattern (usual interstitial pneumonia pattern vs. not).

Finally, methotrexate use appeared to delay the adjusted time to onset of ILD by 3.5 years in the discovery cohort (P = .001), by 3.2 years in the replication cohort (P < .0001), and by 3.5 years in the combined cohort (P < .0001).

“Outside of methotrexate hypersensitivity pneumonitis, methotrexate was not a risk factor for RA-associated ILD in our study. We observed an inverse relationship that was similar whatever the high-resolution CT pattern,” Dr. Juge commented. “But this possible protective effect should be confirmed through a dedicated prospective, randomized, controlled trial.”

“Methotrexate should not be considered as a causal factor for RA-associated ILD, and its [discontinuation] should be discussed through a multidisciplinary discussion,” he recommended. In addition, “this study does not investigate the impact of methotrexate use on RA-associated ILD prognosis.”

The Danish study did not receive any specific funding, and none of its authors reported having any financial disclosures. The multinational study did not receive any specific funding. Dr. Juge disclosed that he had no relevant conflicts of interest, but many of his coauthors reported financial relationships with industry. Dr. Volkmann disclosed consulting for Boehringer Ingelheim and Forbius, and receiving grant support from Forbius and Corbus.

SOURCES: Cordtz R et al. Ann Rheum Dis. 2020;79[suppl 1]:147-8, Abstract OP0232; Juge P-A et al. Ann Rheum Dis. 2020;79[suppl 1]:25, Abstract OP0236.

Being aged older than 65 years was associated with the highest risk of people with rheumatic and musculoskeletal diseases (RMDs) needing hospital treatment for COVID-19, according to the first results to be reported from ReCoVery, the German national COVID-19 registry.

Older patients with RMDs were five times more likely than younger patients to be hospitalized if they tested positive for SARS‑CoV‑2 and developed COVID-19 (odds ratio, 5.1; 95% confidence interval, 2.3-11.4).

The likelihood of hospitalization was also significantly increased by the current or prior use of glucocorticoids (OR, 2.59; 95% CI, 1.2-5.4) and by the presence of cardiovascular disease (OR, 2.27; 95% CI, 1.2-5.4).

“The register is a joint initiative of the German Society for Rheumatology and the Justus Liebig University in Giessen,” explained Anne Regierer, MD, during a live session of the annual European Congress of Rheumatology, held online this year due to COVID-19.

“The current pandemic has changed all of our lives. For patients it brought a lot of uncertainty and fears,” said Dr. Regierer, of the German Rheumatism Research Center Berlin.

“The risk of SARS-CoV-2 infection in patients with inflammatory rheumatic diseases [IRD] is still largely unknown. We still don’t know whether they have a high risk of getting the infection or whether they have a higher risk of a severer case ... therefore there’s an urgent need to have data to generate evidence for the management of our patients.”

Launched at the end of March 2020, the German registry now includes data on 251 patients – 194 of whom have recovered – provided by more than 200 registered rheumatologists. The registry data have now been integrated into the EULAR COVID-19 Database, which is itself part of a global effort to better understand and optimally manage RMD patients during the pandemic.

“The data presented by Dr. Regierer looked at similar outcomes and found quite similar results, which is reassuring,” Kimme Hyrich, MD, PhD, professor of epidemiology at the University of Manchester (England) and a consultant rheumatologist in the Kellgren Centre for Rheumatology at Manchester University Hospitals NHS Foundation Trust, said in an interview.

“We are very grateful for this collaboration [with the German society and others]. Our first publication has looked at hospitalization, but with more data we may have the opportunity to look at less-common outcomes [e.g. death, other COVID complications] or within individual diseases or treatments. So far I don’t think we will come to a different conclusion,” observed Dr. Hyrich, who is on the steering committee for the EULAR COVID-19 Database.

“These initial data are reassuring in that the majority of cases of COVID reported to our database have recovered, including those who were hospitalized,” she said.

Current EULAR advice is to continue treatment with glucocorticoids in patients who are being chronically treated, but to use them at the lowest possible dose.

The objectives of this first analysis of the German registry was to provide a description of the patients who did and did not require hospitalization and those who needed ventilation, as well as look at possible risk factors for hospitalization.

Dr. Regierer reported that, of 192 patients they included – all with a positive lab test for SARS-CoV-2 – 128 (67%) did not require hospital admission. Of those that did (n = 64), 43 (22%) did not need ventilation and 21 (11%) did. Fifteen patients died, all of whom had been hospitalized, and all but one of them had needed ventilation.

Concerning the characteristics of the patients, those who needed hospital treatment with and without ventilation were older than those who were not admitted (70 vs. 65 vs. 54 years, respectively).

“Looking at the sexes, the gender distribution is also interesting. We see 69% females in the nonhospitalized patients, 65% of the inpatients without ventilation, but only 43% females in the ventilated patients. So in this group, the male patients are the majority,” Dr. Regierer observed.

Just over half of all patients in the nonhospitalized and the hospitalized without ventilation groups had IRD in remission, but those in the hospitalized with ventilation group less than one-fifth had their IRD under control.

“Of course we have to keep in mind the small sample sizes,” Dr. Regierer said, but the distribution of patients by disease type was “what you’d expect in clinical care.” The majority of patients in each of the three groups had RA (47%, 56%, and 57%), followed by psoriatic arthritis (19%, 7%, and 14%), axial spondyloarthritis (11%, 5%, and 0%), systemic lupus erythematosus (6%, 2%, and 0%), and vasculitis (1%, 5%, and 5%).

Patients who were hospitalized with and without ventilation were more likely to have more than one comorbidity than those who were not hospitalized with COVID-19.

“The most frequent comorbidity was cardiovascular disease with 58% and 76% in the inpatient groups,” Dr. Regierer reported. One-third of the nonhospitalized patients had a cardiovascular comorbidity.

“If we look at pulmonary disease, we see that 38% of the ventilator patients had an underlying pulmonary disease,” she added. This was in comparison with 19% of the hospitalized without ventilation and 13% of the nonhospitalized patients. Diabetes was another common comorbidity in hospitalized patients with (16%) and without (19%) ventilation versus just 2% of nonhospitalized patients. While these and other comorbidities such as chronic renal insufficiency were associated with higher odds ratios in the multivariate risk factor analysis, they did not reach statistical significance.

With regard to RMD treatments, more than 60% of patients in the hospitalized group had received treatment with glucocorticoids versus 37% of those who did not get admitted. No differences were seen for the other treatments.

Interestingly, “female sex, remission, and use of NSAIDs have an odds ratio smaller than 1. So there might be a lower risk of hospitalization associated with these factors,” Dr. Regierer said.

Dr. Regierer has received grant support and is part of speaker’s bureaus for a variety of pharmaceutical companies. Dr. Hyrich disclosed grant income from Bristol-Myers Squibb, UCB, and Pfizer, and receiving speaker fees from AbbVie.

Being aged older than 65 years was associated with the highest risk of people with rheumatic and musculoskeletal diseases (RMDs) needing hospital treatment for COVID-19, according to the first results to be reported from ReCoVery, the German national COVID-19 registry.

Older patients with RMDs were five times more likely than younger patients to be hospitalized if they tested positive for SARS‑CoV‑2 and developed COVID-19 (odds ratio, 5.1; 95% confidence interval, 2.3-11.4).

The likelihood of hospitalization was also significantly increased by the current or prior use of glucocorticoids (OR, 2.59; 95% CI, 1.2-5.4) and by the presence of cardiovascular disease (OR, 2.27; 95% CI, 1.2-5.4).

“The register is a joint initiative of the German Society for Rheumatology and the Justus Liebig University in Giessen,” explained Anne Regierer, MD, during a live session of the annual European Congress of Rheumatology, held online this year due to COVID-19.

“The current pandemic has changed all of our lives. For patients it brought a lot of uncertainty and fears,” said Dr. Regierer, of the German Rheumatism Research Center Berlin.

“The risk of SARS-CoV-2 infection in patients with inflammatory rheumatic diseases [IRD] is still largely unknown. We still don’t know whether they have a high risk of getting the infection or whether they have a higher risk of a severer case ... therefore there’s an urgent need to have data to generate evidence for the management of our patients.”

Launched at the end of March 2020, the German registry now includes data on 251 patients – 194 of whom have recovered – provided by more than 200 registered rheumatologists. The registry data have now been integrated into the EULAR COVID-19 Database, which is itself part of a global effort to better understand and optimally manage RMD patients during the pandemic.

“The data presented by Dr. Regierer looked at similar outcomes and found quite similar results, which is reassuring,” Kimme Hyrich, MD, PhD, professor of epidemiology at the University of Manchester (England) and a consultant rheumatologist in the Kellgren Centre for Rheumatology at Manchester University Hospitals NHS Foundation Trust, said in an interview.

“We are very grateful for this collaboration [with the German society and others]. Our first publication has looked at hospitalization, but with more data we may have the opportunity to look at less-common outcomes [e.g. death, other COVID complications] or within individual diseases or treatments. So far I don’t think we will come to a different conclusion,” observed Dr. Hyrich, who is on the steering committee for the EULAR COVID-19 Database.

“These initial data are reassuring in that the majority of cases of COVID reported to our database have recovered, including those who were hospitalized,” she said.

Current EULAR advice is to continue treatment with glucocorticoids in patients who are being chronically treated, but to use them at the lowest possible dose.

The objectives of this first analysis of the German registry was to provide a description of the patients who did and did not require hospitalization and those who needed ventilation, as well as look at possible risk factors for hospitalization.

Dr. Regierer reported that, of 192 patients they included – all with a positive lab test for SARS-CoV-2 – 128 (67%) did not require hospital admission. Of those that did (n = 64), 43 (22%) did not need ventilation and 21 (11%) did. Fifteen patients died, all of whom had been hospitalized, and all but one of them had needed ventilation.

Concerning the characteristics of the patients, those who needed hospital treatment with and without ventilation were older than those who were not admitted (70 vs. 65 vs. 54 years, respectively).

“Looking at the sexes, the gender distribution is also interesting. We see 69% females in the nonhospitalized patients, 65% of the inpatients without ventilation, but only 43% females in the ventilated patients. So in this group, the male patients are the majority,” Dr. Regierer observed.

Just over half of all patients in the nonhospitalized and the hospitalized without ventilation groups had IRD in remission, but those in the hospitalized with ventilation group less than one-fifth had their IRD under control.

“Of course we have to keep in mind the small sample sizes,” Dr. Regierer said, but the distribution of patients by disease type was “what you’d expect in clinical care.” The majority of patients in each of the three groups had RA (47%, 56%, and 57%), followed by psoriatic arthritis (19%, 7%, and 14%), axial spondyloarthritis (11%, 5%, and 0%), systemic lupus erythematosus (6%, 2%, and 0%), and vasculitis (1%, 5%, and 5%).

Patients who were hospitalized with and without ventilation were more likely to have more than one comorbidity than those who were not hospitalized with COVID-19.

“The most frequent comorbidity was cardiovascular disease with 58% and 76% in the inpatient groups,” Dr. Regierer reported. One-third of the nonhospitalized patients had a cardiovascular comorbidity.

“If we look at pulmonary disease, we see that 38% of the ventilator patients had an underlying pulmonary disease,” she added. This was in comparison with 19% of the hospitalized without ventilation and 13% of the nonhospitalized patients. Diabetes was another common comorbidity in hospitalized patients with (16%) and without (19%) ventilation versus just 2% of nonhospitalized patients. While these and other comorbidities such as chronic renal insufficiency were associated with higher odds ratios in the multivariate risk factor analysis, they did not reach statistical significance.

With regard to RMD treatments, more than 60% of patients in the hospitalized group had received treatment with glucocorticoids versus 37% of those who did not get admitted. No differences were seen for the other treatments.

Interestingly, “female sex, remission, and use of NSAIDs have an odds ratio smaller than 1. So there might be a lower risk of hospitalization associated with these factors,” Dr. Regierer said.

Dr. Regierer has received grant support and is part of speaker’s bureaus for a variety of pharmaceutical companies. Dr. Hyrich disclosed grant income from Bristol-Myers Squibb, UCB, and Pfizer, and receiving speaker fees from AbbVie.

Being aged older than 65 years was associated with the highest risk of people with rheumatic and musculoskeletal diseases (RMDs) needing hospital treatment for COVID-19, according to the first results to be reported from ReCoVery, the German national COVID-19 registry.

Older patients with RMDs were five times more likely than younger patients to be hospitalized if they tested positive for SARS‑CoV‑2 and developed COVID-19 (odds ratio, 5.1; 95% confidence interval, 2.3-11.4).

The likelihood of hospitalization was also significantly increased by the current or prior use of glucocorticoids (OR, 2.59; 95% CI, 1.2-5.4) and by the presence of cardiovascular disease (OR, 2.27; 95% CI, 1.2-5.4).

“The register is a joint initiative of the German Society for Rheumatology and the Justus Liebig University in Giessen,” explained Anne Regierer, MD, during a live session of the annual European Congress of Rheumatology, held online this year due to COVID-19.

“The current pandemic has changed all of our lives. For patients it brought a lot of uncertainty and fears,” said Dr. Regierer, of the German Rheumatism Research Center Berlin.

“The risk of SARS-CoV-2 infection in patients with inflammatory rheumatic diseases [IRD] is still largely unknown. We still don’t know whether they have a high risk of getting the infection or whether they have a higher risk of a severer case ... therefore there’s an urgent need to have data to generate evidence for the management of our patients.”

Launched at the end of March 2020, the German registry now includes data on 251 patients – 194 of whom have recovered – provided by more than 200 registered rheumatologists. The registry data have now been integrated into the EULAR COVID-19 Database, which is itself part of a global effort to better understand and optimally manage RMD patients during the pandemic.

“The data presented by Dr. Regierer looked at similar outcomes and found quite similar results, which is reassuring,” Kimme Hyrich, MD, PhD, professor of epidemiology at the University of Manchester (England) and a consultant rheumatologist in the Kellgren Centre for Rheumatology at Manchester University Hospitals NHS Foundation Trust, said in an interview.

“We are very grateful for this collaboration [with the German society and others]. Our first publication has looked at hospitalization, but with more data we may have the opportunity to look at less-common outcomes [e.g. death, other COVID complications] or within individual diseases or treatments. So far I don’t think we will come to a different conclusion,” observed Dr. Hyrich, who is on the steering committee for the EULAR COVID-19 Database.

“These initial data are reassuring in that the majority of cases of COVID reported to our database have recovered, including those who were hospitalized,” she said.

Current EULAR advice is to continue treatment with glucocorticoids in patients who are being chronically treated, but to use them at the lowest possible dose.

The objectives of this first analysis of the German registry was to provide a description of the patients who did and did not require hospitalization and those who needed ventilation, as well as look at possible risk factors for hospitalization.

Dr. Regierer reported that, of 192 patients they included – all with a positive lab test for SARS-CoV-2 – 128 (67%) did not require hospital admission. Of those that did (n = 64), 43 (22%) did not need ventilation and 21 (11%) did. Fifteen patients died, all of whom had been hospitalized, and all but one of them had needed ventilation.

Concerning the characteristics of the patients, those who needed hospital treatment with and without ventilation were older than those who were not admitted (70 vs. 65 vs. 54 years, respectively).

“Looking at the sexes, the gender distribution is also interesting. We see 69% females in the nonhospitalized patients, 65% of the inpatients without ventilation, but only 43% females in the ventilated patients. So in this group, the male patients are the majority,” Dr. Regierer observed.

Just over half of all patients in the nonhospitalized and the hospitalized without ventilation groups had IRD in remission, but those in the hospitalized with ventilation group less than one-fifth had their IRD under control.

“Of course we have to keep in mind the small sample sizes,” Dr. Regierer said, but the distribution of patients by disease type was “what you’d expect in clinical care.” The majority of patients in each of the three groups had RA (47%, 56%, and 57%), followed by psoriatic arthritis (19%, 7%, and 14%), axial spondyloarthritis (11%, 5%, and 0%), systemic lupus erythematosus (6%, 2%, and 0%), and vasculitis (1%, 5%, and 5%).

Patients who were hospitalized with and without ventilation were more likely to have more than one comorbidity than those who were not hospitalized with COVID-19.

“The most frequent comorbidity was cardiovascular disease with 58% and 76% in the inpatient groups,” Dr. Regierer reported. One-third of the nonhospitalized patients had a cardiovascular comorbidity.

“If we look at pulmonary disease, we see that 38% of the ventilator patients had an underlying pulmonary disease,” she added. This was in comparison with 19% of the hospitalized without ventilation and 13% of the nonhospitalized patients. Diabetes was another common comorbidity in hospitalized patients with (16%) and without (19%) ventilation versus just 2% of nonhospitalized patients. While these and other comorbidities such as chronic renal insufficiency were associated with higher odds ratios in the multivariate risk factor analysis, they did not reach statistical significance.

With regard to RMD treatments, more than 60% of patients in the hospitalized group had received treatment with glucocorticoids versus 37% of those who did not get admitted. No differences were seen for the other treatments.

Interestingly, “female sex, remission, and use of NSAIDs have an odds ratio smaller than 1. So there might be a lower risk of hospitalization associated with these factors,” Dr. Regierer said.

Dr. Regierer has received grant support and is part of speaker’s bureaus for a variety of pharmaceutical companies. Dr. Hyrich disclosed grant income from Bristol-Myers Squibb, UCB, and Pfizer, and receiving speaker fees from AbbVie.

Patients with rheumatoid arthritis (RA) who are treated with Janus kinase (JAK) inhibitors had the highest risk of developing herpes zoster among newer disease-modifying antirheumatic drugs (DMARDs), according to data released from the German biologics registry.

These are believed to be the first European data on the risk of herpes zoster with JAK inhibitors and showed that the crude incidence rate of herpes zoster per 1,000 patient-years was 24.9 with JAK inhibitors, compared with just 5.8 for controls taking conventional synthetic (cs) DMARDs.

The risk of herpes zoster was also increased with other biologic (b) and targeted synthetic (ts) DMARDs that were assessed, with crude rates per 1,000 patient-years of 10.4 for monoclonal tumor necrosis factor inhibitors (TNFi), 10.5 for B-cell targeted therapies, 9.4 for T-cell costimulation modulators, 9.0 for soluble TNF receptors, and 8.5 for interleukin (IL)-6 inhibitors.

Overall, JAK inhibitor treatment was associated with a fivefold higher risk of herpes zoster (hazard ratio, 5.0; P < .0001), compared with the control csDMARD population after adjustment using an inverse probability weights (IPW) method.

“The general risk of herpes zoster is [twofold] higher in patients with rheumatoid arthritis when you compare it with the general population,” said Anja Strangfeld, MD of the German Research Center, Berlin, and one of the three RABBIT [Rheumatoide Arthritis: Biobachtung der Biologika-Therapie] principal investigators.

“If you think of all the treatments that RA patients get, then the risk is further increased with bDMARD and [JAK inhibitor] treatments,” she added in an interview. While the risk was highest with JAK inhibitors, “we also saw that monoclonal TNF antibodies as well as all the other biologic DMARD treatments have a higher risk of herpes zoster in RA patients, compared to csDMARD therapy,” Dr. Strangfeld said.

Adjusted IPW HR for the other RA treatments showed an increased herpes zoster risk for all but the soluble TNF receptor agents, at 1.6 for IL-6 inhibitors (P = .0045) and monoclonal TNFi antibodies (P = .0003), and 1.7 for B-cell targeted therapies (P = .00026) and T-cell costimulation modulators (P = .0048).

Dr. Strangfeld presented these data during the annual European Congress of Rheumatology, held online this year due to COVID-19. The analysis included 12,470 patients with RA enrolled in RABBIT from 2007 onward and who had been treated with monoclonal TNF inhibitor antibodies, cell-targeted therapies, and tsDMARDs such as JAK inhibitors. In all, at the data cutoff at the end of April 2019, 452 cases of herpes zoster were recorded in 433 patients, of which 52 cases were serious.

“The reactivation of the varicella zoster virus causing the herpes zoster is triggered by a decline of cellular immunity. This can be due to aging or immune suppression of any kind,” Dr. Strangfeld said in her presentation.

“The Cox regression [analysis] revealed that higher age and intake of glucocorticoids were associated with an increased risk of herpes zoster,” she reported, with a dose dependent increase with glucocorticoids. IPW HR for age per 10 years was 1.3 (P < .0001) and 1.9 (P = .0022) for higher doses of glucocorticoids (>10 vs. 0 mg/day).

Commenting on the study, rheumatologist and epidemiologist Loreto Carmona, MD, PhD, said: “This is a very interesting study. The results are confident and precise. The frequency of herpes zoster infection [based on crude incidence rate estimates] is very high. However, we must focus on the [multivariable with IPW] analysis after taking into account baseline risk.”

Dr. Carmona, who is the chair of the congress’s Abstract Selection Committee and is the scientific director of the Instituto de Salud Musculoesquelética in Madrid, added: “Having a disease with high levels of activity or a disease refractory to treatments [both of which were very likely used in creating the IPW] levels off the risk a bit. Also, because RA by itself, glucocorticoids, and age all increase the risk. Still, jakinibs [JAK inhibitors] stand out as the treatment related to higher risk of herpes zoster infection.”

Dr. Strangfeld and fellow RABBIT investigators have previously looked at the risk of herpes zoster in patients treated with anti–TNF-alpha agents (JAMA. 2009;301[7]:737-44). They found that monoclonal anti–TNF-alpha agents may be associated with increased risk of herpes zoster, which is now confirmed by the current analysis. The reason for looking at herpes zoster risk again is that since that first analysis, many more therapies have become available for RA during the past 10 years, notably the tsDMARDs.

Herpes zoster may not always be a serious event, Dr. Strangfeld said in the interview, “but it diminishes your quality of life; it can also be associated with pain and may be followed by postherpetic neuralgia, which is very painful.” With new herpes zoster vaccinations available, it is now possible to vaccinate patients more easily. “This is advisable for all kinds of treatments,” she said.

“What we found was quite in agreement with the data that we know from the U.S., from the observational studies, for example from the Corrona database,” Dr. Strangfeld stated. The key finding is that the risk of herpes zoster is increased to some level, almost regardless of which drug is chosen, she said. “This gives a clear message that systematic herpes zoster vaccination should be done in patients with RA,” she suggested.

The German biologics registry RABBIT is supported by a joint unconditional grant from AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Hexal, Lilly, Merck Sharp & Dohme, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. Dr. Strangfeld has received speaker fees from AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, Sanofi-Aventis, and UCB. Dr. Carmona had no relevant conflicts of interest to disclose.

SOURCE: Strangfeld A et al. Ann Rheum Dis. 2020;79[suppl 1]:150. Abstract OP0238.

Patients with rheumatoid arthritis (RA) who are treated with Janus kinase (JAK) inhibitors had the highest risk of developing herpes zoster among newer disease-modifying antirheumatic drugs (DMARDs), according to data released from the German biologics registry.

These are believed to be the first European data on the risk of herpes zoster with JAK inhibitors and showed that the crude incidence rate of herpes zoster per 1,000 patient-years was 24.9 with JAK inhibitors, compared with just 5.8 for controls taking conventional synthetic (cs) DMARDs.

The risk of herpes zoster was also increased with other biologic (b) and targeted synthetic (ts) DMARDs that were assessed, with crude rates per 1,000 patient-years of 10.4 for monoclonal tumor necrosis factor inhibitors (TNFi), 10.5 for B-cell targeted therapies, 9.4 for T-cell costimulation modulators, 9.0 for soluble TNF receptors, and 8.5 for interleukin (IL)-6 inhibitors.

Overall, JAK inhibitor treatment was associated with a fivefold higher risk of herpes zoster (hazard ratio, 5.0; P < .0001), compared with the control csDMARD population after adjustment using an inverse probability weights (IPW) method.

“The general risk of herpes zoster is [twofold] higher in patients with rheumatoid arthritis when you compare it with the general population,” said Anja Strangfeld, MD of the German Research Center, Berlin, and one of the three RABBIT [Rheumatoide Arthritis: Biobachtung der Biologika-Therapie] principal investigators.

“If you think of all the treatments that RA patients get, then the risk is further increased with bDMARD and [JAK inhibitor] treatments,” she added in an interview. While the risk was highest with JAK inhibitors, “we also saw that monoclonal TNF antibodies as well as all the other biologic DMARD treatments have a higher risk of herpes zoster in RA patients, compared to csDMARD therapy,” Dr. Strangfeld said.

Adjusted IPW HR for the other RA treatments showed an increased herpes zoster risk for all but the soluble TNF receptor agents, at 1.6 for IL-6 inhibitors (P = .0045) and monoclonal TNFi antibodies (P = .0003), and 1.7 for B-cell targeted therapies (P = .00026) and T-cell costimulation modulators (P = .0048).

Dr. Strangfeld presented these data during the annual European Congress of Rheumatology, held online this year due to COVID-19. The analysis included 12,470 patients with RA enrolled in RABBIT from 2007 onward and who had been treated with monoclonal TNF inhibitor antibodies, cell-targeted therapies, and tsDMARDs such as JAK inhibitors. In all, at the data cutoff at the end of April 2019, 452 cases of herpes zoster were recorded in 433 patients, of which 52 cases were serious.

“The reactivation of the varicella zoster virus causing the herpes zoster is triggered by a decline of cellular immunity. This can be due to aging or immune suppression of any kind,” Dr. Strangfeld said in her presentation.

“The Cox regression [analysis] revealed that higher age and intake of glucocorticoids were associated with an increased risk of herpes zoster,” she reported, with a dose dependent increase with glucocorticoids. IPW HR for age per 10 years was 1.3 (P < .0001) and 1.9 (P = .0022) for higher doses of glucocorticoids (>10 vs. 0 mg/day).

Commenting on the study, rheumatologist and epidemiologist Loreto Carmona, MD, PhD, said: “This is a very interesting study. The results are confident and precise. The frequency of herpes zoster infection [based on crude incidence rate estimates] is very high. However, we must focus on the [multivariable with IPW] analysis after taking into account baseline risk.”

Dr. Carmona, who is the chair of the congress’s Abstract Selection Committee and is the scientific director of the Instituto de Salud Musculoesquelética in Madrid, added: “Having a disease with high levels of activity or a disease refractory to treatments [both of which were very likely used in creating the IPW] levels off the risk a bit. Also, because RA by itself, glucocorticoids, and age all increase the risk. Still, jakinibs [JAK inhibitors] stand out as the treatment related to higher risk of herpes zoster infection.”

Dr. Strangfeld and fellow RABBIT investigators have previously looked at the risk of herpes zoster in patients treated with anti–TNF-alpha agents (JAMA. 2009;301[7]:737-44). They found that monoclonal anti–TNF-alpha agents may be associated with increased risk of herpes zoster, which is now confirmed by the current analysis. The reason for looking at herpes zoster risk again is that since that first analysis, many more therapies have become available for RA during the past 10 years, notably the tsDMARDs.

Herpes zoster may not always be a serious event, Dr. Strangfeld said in the interview, “but it diminishes your quality of life; it can also be associated with pain and may be followed by postherpetic neuralgia, which is very painful.” With new herpes zoster vaccinations available, it is now possible to vaccinate patients more easily. “This is advisable for all kinds of treatments,” she said.

“What we found was quite in agreement with the data that we know from the U.S., from the observational studies, for example from the Corrona database,” Dr. Strangfeld stated. The key finding is that the risk of herpes zoster is increased to some level, almost regardless of which drug is chosen, she said. “This gives a clear message that systematic herpes zoster vaccination should be done in patients with RA,” she suggested.

The German biologics registry RABBIT is supported by a joint unconditional grant from AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Hexal, Lilly, Merck Sharp & Dohme, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. Dr. Strangfeld has received speaker fees from AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, Sanofi-Aventis, and UCB. Dr. Carmona had no relevant conflicts of interest to disclose.

SOURCE: Strangfeld A et al. Ann Rheum Dis. 2020;79[suppl 1]:150. Abstract OP0238.

Patients with rheumatoid arthritis (RA) who are treated with Janus kinase (JAK) inhibitors had the highest risk of developing herpes zoster among newer disease-modifying antirheumatic drugs (DMARDs), according to data released from the German biologics registry.

These are believed to be the first European data on the risk of herpes zoster with JAK inhibitors and showed that the crude incidence rate of herpes zoster per 1,000 patient-years was 24.9 with JAK inhibitors, compared with just 5.8 for controls taking conventional synthetic (cs) DMARDs.

The risk of herpes zoster was also increased with other biologic (b) and targeted synthetic (ts) DMARDs that were assessed, with crude rates per 1,000 patient-years of 10.4 for monoclonal tumor necrosis factor inhibitors (TNFi), 10.5 for B-cell targeted therapies, 9.4 for T-cell costimulation modulators, 9.0 for soluble TNF receptors, and 8.5 for interleukin (IL)-6 inhibitors.

Overall, JAK inhibitor treatment was associated with a fivefold higher risk of herpes zoster (hazard ratio, 5.0; P < .0001), compared with the control csDMARD population after adjustment using an inverse probability weights (IPW) method.

“The general risk of herpes zoster is [twofold] higher in patients with rheumatoid arthritis when you compare it with the general population,” said Anja Strangfeld, MD of the German Research Center, Berlin, and one of the three RABBIT [Rheumatoide Arthritis: Biobachtung der Biologika-Therapie] principal investigators.

“If you think of all the treatments that RA patients get, then the risk is further increased with bDMARD and [JAK inhibitor] treatments,” she added in an interview. While the risk was highest with JAK inhibitors, “we also saw that monoclonal TNF antibodies as well as all the other biologic DMARD treatments have a higher risk of herpes zoster in RA patients, compared to csDMARD therapy,” Dr. Strangfeld said.

Adjusted IPW HR for the other RA treatments showed an increased herpes zoster risk for all but the soluble TNF receptor agents, at 1.6 for IL-6 inhibitors (P = .0045) and monoclonal TNFi antibodies (P = .0003), and 1.7 for B-cell targeted therapies (P = .00026) and T-cell costimulation modulators (P = .0048).

Dr. Strangfeld presented these data during the annual European Congress of Rheumatology, held online this year due to COVID-19. The analysis included 12,470 patients with RA enrolled in RABBIT from 2007 onward and who had been treated with monoclonal TNF inhibitor antibodies, cell-targeted therapies, and tsDMARDs such as JAK inhibitors. In all, at the data cutoff at the end of April 2019, 452 cases of herpes zoster were recorded in 433 patients, of which 52 cases were serious.

“The reactivation of the varicella zoster virus causing the herpes zoster is triggered by a decline of cellular immunity. This can be due to aging or immune suppression of any kind,” Dr. Strangfeld said in her presentation.

“The Cox regression [analysis] revealed that higher age and intake of glucocorticoids were associated with an increased risk of herpes zoster,” she reported, with a dose dependent increase with glucocorticoids. IPW HR for age per 10 years was 1.3 (P < .0001) and 1.9 (P = .0022) for higher doses of glucocorticoids (>10 vs. 0 mg/day).

Commenting on the study, rheumatologist and epidemiologist Loreto Carmona, MD, PhD, said: “This is a very interesting study. The results are confident and precise. The frequency of herpes zoster infection [based on crude incidence rate estimates] is very high. However, we must focus on the [multivariable with IPW] analysis after taking into account baseline risk.”

Dr. Carmona, who is the chair of the congress’s Abstract Selection Committee and is the scientific director of the Instituto de Salud Musculoesquelética in Madrid, added: “Having a disease with high levels of activity or a disease refractory to treatments [both of which were very likely used in creating the IPW] levels off the risk a bit. Also, because RA by itself, glucocorticoids, and age all increase the risk. Still, jakinibs [JAK inhibitors] stand out as the treatment related to higher risk of herpes zoster infection.”

Dr. Strangfeld and fellow RABBIT investigators have previously looked at the risk of herpes zoster in patients treated with anti–TNF-alpha agents (JAMA. 2009;301[7]:737-44). They found that monoclonal anti–TNF-alpha agents may be associated with increased risk of herpes zoster, which is now confirmed by the current analysis. The reason for looking at herpes zoster risk again is that since that first analysis, many more therapies have become available for RA during the past 10 years, notably the tsDMARDs.

Herpes zoster may not always be a serious event, Dr. Strangfeld said in the interview, “but it diminishes your quality of life; it can also be associated with pain and may be followed by postherpetic neuralgia, which is very painful.” With new herpes zoster vaccinations available, it is now possible to vaccinate patients more easily. “This is advisable for all kinds of treatments,” she said.

“What we found was quite in agreement with the data that we know from the U.S., from the observational studies, for example from the Corrona database,” Dr. Strangfeld stated. The key finding is that the risk of herpes zoster is increased to some level, almost regardless of which drug is chosen, she said. “This gives a clear message that systematic herpes zoster vaccination should be done in patients with RA,” she suggested.

The German biologics registry RABBIT is supported by a joint unconditional grant from AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Hexal, Lilly, Merck Sharp & Dohme, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. Dr. Strangfeld has received speaker fees from AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, Sanofi-Aventis, and UCB. Dr. Carmona had no relevant conflicts of interest to disclose.

SOURCE: Strangfeld A et al. Ann Rheum Dis. 2020;79[suppl 1]:150. Abstract OP0238.

The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.

“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”

Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.

In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.

The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.

“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.

As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.

Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.

Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.

“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”

“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”

It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.

“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.

The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.

Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.

Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.

“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”

This article first appeared on Medscape.com.

The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.

“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”

Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.

In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.

The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.

“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.

As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.

Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.

Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.

“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”

“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”

It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.

“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.

The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.

Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.

Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.

“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”

This article first appeared on Medscape.com.

The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.

“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”

Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.

In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.

The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.

“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.

As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.

Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.

Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.

“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”

“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”

It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.

“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.

The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.

Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.

Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.

“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”

This article first appeared on Medscape.com.

In patients with rheumatoid arthritis (RA), strategies to prevent cardiovascular events, such as treating hypertension, encouraging patients to stop smoking, and reinforcing statin therapy, may be especially important, regardless of whether they have a history of coronary artery disease because their risk for adverse cardiovascular outcomes is significantly greater than for patients who have neither RA nor coronary artery disease (CAD), a large population-based study from Denmark suggests.

“Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalized treatment strategies,” wrote Brian B. Løgstrup, MD, PhD, DMSc, of Aarhus (Denmark) University Hospital, and his colleagues.

The study, published in Annals of the Rheumatic Diseases, analyzed 125,331 patients with and without CAD in the Western Denmark Heart Registry who had coronary angiography from 2003 through 2016. The cohort included 671 RA patients with no confirmed CAD and 1,061 RA patients who had CAD.

The study makes a significant contribution to the literature in reporting on the additive risk of RA and CAD, said Christie M. Bartels, MD, associate professor in the division of rheumatology at the University of Wisconsin, Madison. “Even among patients with both conditions [RA and CVD], they were less likely to get statin therapy,” she said, noting that the 82.6% of study patients with both CAD and RA were on statins vs. 86.5% of those with CAD alone, while the former had significantly higher rates of hypertension – 64.3% vs. 58.8%. “We’re doing a less effective job on secondary prevention,” she said. The anti-inflammatory properties of statins can also have an additive benefit in RA, she noted.

“This study shows that the rheumatologist can play a role in reinforcing the importance of primary and secondary cardiovascular disease prevention – meaning hypertension control, counseling patients to stop smoking and following up on statin therapy in RA,” Dr. Bartels added.

The study presents two novel findings, Dr. Løgstrup and colleagues noted:

• That RA confers a statistically significant, “but numerically marginally,” heightened risk of cardiovascular events other than stroke.
• Among patients with CAD, RA confers an increased risk of cardiac and all-cause death as well as MI and major adverse cardiovascular events (MACE).

“These finding indicate that RA may have a potential impact for precipitating cardiovascular events beyond CAD and, even more importantly, that RA seems to exacerbate the clinical risk of cardiovascular events in the presence of CAD,” Dr. Løgstrup and colleagues wrote.

The study found that patients with neither RA nor CAD had the lowest 10-year rates of MI (2.7%), ischemic stroke (2.9%), all-cause death (21.6%), cardiac death (2.3%), and MACE (7.3%).

By comparison, those with RA but no CAD had 10-year rates of 3.8% for MI, 5.5% for stroke, 35.6% for all-cause death, 3% for cardiac death, and 11.5% for MACE. Rates for those outcomes for people with CAD but no RA were 9.9% for MI, 4.6% for stroke, 33.3% for all-cause death, 7% for cardiac death, and 19.1% for MACE.

For patients with both RA and CAD, 10-year rates were 12.2% for MI, 4.4% for stroke, 49% for all-cause death, 10.9% for cardiac death, and 24.3% for MACE.

The researchers also performed a risk adjustment analysis based on potential confounding variables across the different groups, such as age, gender, comorbidities including diabetes and hypertension, active smoking status, and anticoagulant, antiplatelet, and statin therapy. The adjusted analysis revealed that patients with RA alone had a 63% greater risk of MI, 68% greater risk for stroke, 42% greater risk for all-cause death, 25% greater risk for cardiac death, and 60% greater risk for MACE than did people who had neither RA nor CAD.

For people with both RA and CAD, the adjusted risks were significantly higher when compared to people with neither: more than four times greater for MI and MACE, 55% greater for stroke, almost double for all-cause death, and 3.7 times greater for cardiac death. People with CAD but no RA also had higher adjusted risk rates compared to people with neither, but had variable rates when compared to people with RA but no CAD, and significantly lower adjusted rates compared to people with both.

The nature of CAD was also a factor, Dr. Løgstrup and colleagues noted. “We found more non-obstructive CAD but no increased incidence of one-vessel, two-vessel, and three-vessel disease in patients with RA than in patients without RA,” they wrote. That’s in line with other published studies (Semin Arthritis Rheum. 2010;40[3]:215–21 and J Rheumatol. 2007;34[5]:937–42), but counter to a study that found increased plaque burden and higher rates of multivessel disease among people with RA (Ann Rheum Dis. 2014;73:1797–804). Differences in methodology, vessel disease definitions, and study population may explain these deviations.

The study authors did not declare any outside source of funding or any competing interests.

Dr. Bartels disclosed receiving institutional grant funding through Pfizer.

SOURCE: Løgstrup BB et al. Ann Rheum Dis. 2020 May 29. doi: 10.1136/annrheumdis-2020-217154.

In patients with rheumatoid arthritis (RA), strategies to prevent cardiovascular events, such as treating hypertension, encouraging patients to stop smoking, and reinforcing statin therapy, may be especially important, regardless of whether they have a history of coronary artery disease because their risk for adverse cardiovascular outcomes is significantly greater than for patients who have neither RA nor coronary artery disease (CAD), a large population-based study from Denmark suggests.

“Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalized treatment strategies,” wrote Brian B. Løgstrup, MD, PhD, DMSc, of Aarhus (Denmark) University Hospital, and his colleagues.

The study, published in Annals of the Rheumatic Diseases, analyzed 125,331 patients with and without CAD in the Western Denmark Heart Registry who had coronary angiography from 2003 through 2016. The cohort included 671 RA patients with no confirmed CAD and 1,061 RA patients who had CAD.

The study makes a significant contribution to the literature in reporting on the additive risk of RA and CAD, said Christie M. Bartels, MD, associate professor in the division of rheumatology at the University of Wisconsin, Madison. “Even among patients with both conditions [RA and CVD], they were less likely to get statin therapy,” she said, noting that the 82.6% of study patients with both CAD and RA were on statins vs. 86.5% of those with CAD alone, while the former had significantly higher rates of hypertension – 64.3% vs. 58.8%. “We’re doing a less effective job on secondary prevention,” she said. The anti-inflammatory properties of statins can also have an additive benefit in RA, she noted.

“This study shows that the rheumatologist can play a role in reinforcing the importance of primary and secondary cardiovascular disease prevention – meaning hypertension control, counseling patients to stop smoking and following up on statin therapy in RA,” Dr. Bartels added.

The study presents two novel findings, Dr. Løgstrup and colleagues noted:

• That RA confers a statistically significant, “but numerically marginally,” heightened risk of cardiovascular events other than stroke.
• Among patients with CAD, RA confers an increased risk of cardiac and all-cause death as well as MI and major adverse cardiovascular events (MACE).

“These finding indicate that RA may have a potential impact for precipitating cardiovascular events beyond CAD and, even more importantly, that RA seems to exacerbate the clinical risk of cardiovascular events in the presence of CAD,” Dr. Løgstrup and colleagues wrote.

The study found that patients with neither RA nor CAD had the lowest 10-year rates of MI (2.7%), ischemic stroke (2.9%), all-cause death (21.6%), cardiac death (2.3%), and MACE (7.3%).

By comparison, those with RA but no CAD had 10-year rates of 3.8% for MI, 5.5% for stroke, 35.6% for all-cause death, 3% for cardiac death, and 11.5% for MACE. Rates for those outcomes for people with CAD but no RA were 9.9% for MI, 4.6% for stroke, 33.3% for all-cause death, 7% for cardiac death, and 19.1% for MACE.

For patients with both RA and CAD, 10-year rates were 12.2% for MI, 4.4% for stroke, 49% for all-cause death, 10.9% for cardiac death, and 24.3% for MACE.

The researchers also performed a risk adjustment analysis based on potential confounding variables across the different groups, such as age, gender, comorbidities including diabetes and hypertension, active smoking status, and anticoagulant, antiplatelet, and statin therapy. The adjusted analysis revealed that patients with RA alone had a 63% greater risk of MI, 68% greater risk for stroke, 42% greater risk for all-cause death, 25% greater risk for cardiac death, and 60% greater risk for MACE than did people who had neither RA nor CAD.

For people with both RA and CAD, the adjusted risks were significantly higher when compared to people with neither: more than four times greater for MI and MACE, 55% greater for stroke, almost double for all-cause death, and 3.7 times greater for cardiac death. People with CAD but no RA also had higher adjusted risk rates compared to people with neither, but had variable rates when compared to people with RA but no CAD, and significantly lower adjusted rates compared to people with both.

The nature of CAD was also a factor, Dr. Løgstrup and colleagues noted. “We found more non-obstructive CAD but no increased incidence of one-vessel, two-vessel, and three-vessel disease in patients with RA than in patients without RA,” they wrote. That’s in line with other published studies (Semin Arthritis Rheum. 2010;40[3]:215–21 and J Rheumatol. 2007;34[5]:937–42), but counter to a study that found increased plaque burden and higher rates of multivessel disease among people with RA (Ann Rheum Dis. 2014;73:1797–804). Differences in methodology, vessel disease definitions, and study population may explain these deviations.

The study authors did not declare any outside source of funding or any competing interests.

Dr. Bartels disclosed receiving institutional grant funding through Pfizer.

SOURCE: Løgstrup BB et al. Ann Rheum Dis. 2020 May 29. doi: 10.1136/annrheumdis-2020-217154.

In patients with rheumatoid arthritis (RA), strategies to prevent cardiovascular events, such as treating hypertension, encouraging patients to stop smoking, and reinforcing statin therapy, may be especially important, regardless of whether they have a history of coronary artery disease because their risk for adverse cardiovascular outcomes is significantly greater than for patients who have neither RA nor coronary artery disease (CAD), a large population-based study from Denmark suggests.

“Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalized treatment strategies,” wrote Brian B. Løgstrup, MD, PhD, DMSc, of Aarhus (Denmark) University Hospital, and his colleagues.

The study, published in Annals of the Rheumatic Diseases, analyzed 125,331 patients with and without CAD in the Western Denmark Heart Registry who had coronary angiography from 2003 through 2016. The cohort included 671 RA patients with no confirmed CAD and 1,061 RA patients who had CAD.

The study makes a significant contribution to the literature in reporting on the additive risk of RA and CAD, said Christie M. Bartels, MD, associate professor in the division of rheumatology at the University of Wisconsin, Madison. “Even among patients with both conditions [RA and CVD], they were less likely to get statin therapy,” she said, noting that the 82.6% of study patients with both CAD and RA were on statins vs. 86.5% of those with CAD alone, while the former had significantly higher rates of hypertension – 64.3% vs. 58.8%. “We’re doing a less effective job on secondary prevention,” she said. The anti-inflammatory properties of statins can also have an additive benefit in RA, she noted.

“This study shows that the rheumatologist can play a role in reinforcing the importance of primary and secondary cardiovascular disease prevention – meaning hypertension control, counseling patients to stop smoking and following up on statin therapy in RA,” Dr. Bartels added.

The study presents two novel findings, Dr. Løgstrup and colleagues noted:

• That RA confers a statistically significant, “but numerically marginally,” heightened risk of cardiovascular events other than stroke.
• Among patients with CAD, RA confers an increased risk of cardiac and all-cause death as well as MI and major adverse cardiovascular events (MACE).

“These finding indicate that RA may have a potential impact for precipitating cardiovascular events beyond CAD and, even more importantly, that RA seems to exacerbate the clinical risk of cardiovascular events in the presence of CAD,” Dr. Løgstrup and colleagues wrote.

The study found that patients with neither RA nor CAD had the lowest 10-year rates of MI (2.7%), ischemic stroke (2.9%), all-cause death (21.6%), cardiac death (2.3%), and MACE (7.3%).

By comparison, those with RA but no CAD had 10-year rates of 3.8% for MI, 5.5% for stroke, 35.6% for all-cause death, 3% for cardiac death, and 11.5% for MACE. Rates for those outcomes for people with CAD but no RA were 9.9% for MI, 4.6% for stroke, 33.3% for all-cause death, 7% for cardiac death, and 19.1% for MACE.

For patients with both RA and CAD, 10-year rates were 12.2% for MI, 4.4% for stroke, 49% for all-cause death, 10.9% for cardiac death, and 24.3% for MACE.

The researchers also performed a risk adjustment analysis based on potential confounding variables across the different groups, such as age, gender, comorbidities including diabetes and hypertension, active smoking status, and anticoagulant, antiplatelet, and statin therapy. The adjusted analysis revealed that patients with RA alone had a 63% greater risk of MI, 68% greater risk for stroke, 42% greater risk for all-cause death, 25% greater risk for cardiac death, and 60% greater risk for MACE than did people who had neither RA nor CAD.

For people with both RA and CAD, the adjusted risks were significantly higher when compared to people with neither: more than four times greater for MI and MACE, 55% greater for stroke, almost double for all-cause death, and 3.7 times greater for cardiac death. People with CAD but no RA also had higher adjusted risk rates compared to people with neither, but had variable rates when compared to people with RA but no CAD, and significantly lower adjusted rates compared to people with both.

The nature of CAD was also a factor, Dr. Løgstrup and colleagues noted. “We found more non-obstructive CAD but no increased incidence of one-vessel, two-vessel, and three-vessel disease in patients with RA than in patients without RA,” they wrote. That’s in line with other published studies (Semin Arthritis Rheum. 2010;40[3]:215–21 and J Rheumatol. 2007;34[5]:937–42), but counter to a study that found increased plaque burden and higher rates of multivessel disease among people with RA (Ann Rheum Dis. 2014;73:1797–804). Differences in methodology, vessel disease definitions, and study population may explain these deviations.

The study authors did not declare any outside source of funding or any competing interests.

Dr. Bartels disclosed receiving institutional grant funding through Pfizer.

SOURCE: Løgstrup BB et al. Ann Rheum Dis. 2020 May 29. doi: 10.1136/annrheumdis-2020-217154.

Unacceptable pain more often remains among patients with early, methotrexate-refractory (RA who move on to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine than biologic combination therapy with the tumor necrosis factor inhibitor infliximab (Remicade) plus methotrexate, according to findings from 21 months of follow-up in a post hoc analysis of data from the randomized, controlled Swedish Farmacotherapy (SWEFOT) trial.

Although RA patients who took biologic combination therapy had 32% lower risk for unacceptable pain (rated at >40 mm on a 0- to 100-mm visual analog scale) at 21 months, they still had no difference from patients taking triple therapy in the rate of pain described as refractory, or unacceptable despite inflammation control (C-reactive protein <10 mg/L).

While these results lend “some support to a better effect on long-term pain for the biological treatment, compared with triple therapy ... our findings are also in line with insufficient effects of current treatment strategies to prevent development of inflammation-independent pain components, warranting early alternative treatment approaches in affected patients,” Tor Olofsson, MD, PhD, of Lund (Sweden) University, and colleagues wrote in Arthritis Care & Research.

The pain outcomes analyzed in this post hoc study were all secondary outcomes of the original open-label SWEFOT trial, which during 2002-2005 enrolled 258 RA patients with less than a year of symptoms who did not reach low disease activity (28-joint Disease Activity Score ≤3.2) after 3 months of methotrexate and randomized them to an addition of either infliximab (3 mg/kg rounded up to nearest 100-mg increment) or sulfasalazine 1,000 mg twice daily plus hydroxychloroquine 400 mg once daily.

Overall, 90 of 128 patients in the infliximab group and 74 of 130 in the triple-therapy group continued the protocol until the 21-month follow-up. Patients in the infliximab group had a significantly lower area under the curve for visual analog scale for pain, most of which was accounted for during months 9-21. The percentage of patients in the infliximab group with unacceptable pain also dropped significantly from 57% at randomization to 32% at 21 months, while no difference was seen for triple therapy patients, of whom 45% had unacceptable pain at 21 months.

While patients in the infliximab group had a significantly lower risk of unacceptable pain without inflammatory control at 21 months, neither treatment arm showed a within-group difference in refractory pain from randomization to the 21-month follow-up.

Nearly one-third of patients overall still reported unacceptable pain 21 months after addition of either infliximab or sulfasalazine plus hydroxychloroquine. And at that time point, refractory pain constituted 82% of all unacceptable pain. “Notably, this pattern – with a domination of refractory pain – was evident already 3 months after starting combination therapy,” Dr. Olofsson and colleagues wrote.

The original SWEFOT study was supported in part by a grant from the Swedish Rheumatism Association, and in part by an annual unrestricted grant from Schering-Plough Sweden (now Merck Sharp & Dohme). The post hoc analysis was supported by Lund University and the Kockska Foundation, the Swedish Research Council, and the Stockholm County Council. Two authors disclosed financial relationships with multiple pharmaceutical companies.

jevans@mdedge.com

SOURCE: Olofsson T et al. Arthritis Care Res. 2020 May 20. doi: 10.1002/acr.24264.

Unacceptable pain more often remains among patients with early, methotrexate-refractory (RA who move on to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine than biologic combination therapy with the tumor necrosis factor inhibitor infliximab (Remicade) plus methotrexate, according to findings from 21 months of follow-up in a post hoc analysis of data from the randomized, controlled Swedish Farmacotherapy (SWEFOT) trial.

Although RA patients who took biologic combination therapy had 32% lower risk for unacceptable pain (rated at >40 mm on a 0- to 100-mm visual analog scale) at 21 months, they still had no difference from patients taking triple therapy in the rate of pain described as refractory, or unacceptable despite inflammation control (C-reactive protein <10 mg/L).

While these results lend “some support to a better effect on long-term pain for the biological treatment, compared with triple therapy ... our findings are also in line with insufficient effects of current treatment strategies to prevent development of inflammation-independent pain components, warranting early alternative treatment approaches in affected patients,” Tor Olofsson, MD, PhD, of Lund (Sweden) University, and colleagues wrote in Arthritis Care & Research.

The pain outcomes analyzed in this post hoc study were all secondary outcomes of the original open-label SWEFOT trial, which during 2002-2005 enrolled 258 RA patients with less than a year of symptoms who did not reach low disease activity (28-joint Disease Activity Score ≤3.2) after 3 months of methotrexate and randomized them to an addition of either infliximab (3 mg/kg rounded up to nearest 100-mg increment) or sulfasalazine 1,000 mg twice daily plus hydroxychloroquine 400 mg once daily.

Overall, 90 of 128 patients in the infliximab group and 74 of 130 in the triple-therapy group continued the protocol until the 21-month follow-up. Patients in the infliximab group had a significantly lower area under the curve for visual analog scale for pain, most of which was accounted for during months 9-21. The percentage of patients in the infliximab group with unacceptable pain also dropped significantly from 57% at randomization to 32% at 21 months, while no difference was seen for triple therapy patients, of whom 45% had unacceptable pain at 21 months.

While patients in the infliximab group had a significantly lower risk of unacceptable pain without inflammatory control at 21 months, neither treatment arm showed a within-group difference in refractory pain from randomization to the 21-month follow-up.

Nearly one-third of patients overall still reported unacceptable pain 21 months after addition of either infliximab or sulfasalazine plus hydroxychloroquine. And at that time point, refractory pain constituted 82% of all unacceptable pain. “Notably, this pattern – with a domination of refractory pain – was evident already 3 months after starting combination therapy,” Dr. Olofsson and colleagues wrote.

The original SWEFOT study was supported in part by a grant from the Swedish Rheumatism Association, and in part by an annual unrestricted grant from Schering-Plough Sweden (now Merck Sharp & Dohme). The post hoc analysis was supported by Lund University and the Kockska Foundation, the Swedish Research Council, and the Stockholm County Council. Two authors disclosed financial relationships with multiple pharmaceutical companies.

jevans@mdedge.com

SOURCE: Olofsson T et al. Arthritis Care Res. 2020 May 20. doi: 10.1002/acr.24264.

Unacceptable pain more often remains among patients with early, methotrexate-refractory (RA who move on to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine than biologic combination therapy with the tumor necrosis factor inhibitor infliximab (Remicade) plus methotrexate, according to findings from 21 months of follow-up in a post hoc analysis of data from the randomized, controlled Swedish Farmacotherapy (SWEFOT) trial.

Although RA patients who took biologic combination therapy had 32% lower risk for unacceptable pain (rated at >40 mm on a 0- to 100-mm visual analog scale) at 21 months, they still had no difference from patients taking triple therapy in the rate of pain described as refractory, or unacceptable despite inflammation control (C-reactive protein <10 mg/L).

While these results lend “some support to a better effect on long-term pain for the biological treatment, compared with triple therapy ... our findings are also in line with insufficient effects of current treatment strategies to prevent development of inflammation-independent pain components, warranting early alternative treatment approaches in affected patients,” Tor Olofsson, MD, PhD, of Lund (Sweden) University, and colleagues wrote in Arthritis Care & Research.

The pain outcomes analyzed in this post hoc study were all secondary outcomes of the original open-label SWEFOT trial, which during 2002-2005 enrolled 258 RA patients with less than a year of symptoms who did not reach low disease activity (28-joint Disease Activity Score ≤3.2) after 3 months of methotrexate and randomized them to an addition of either infliximab (3 mg/kg rounded up to nearest 100-mg increment) or sulfasalazine 1,000 mg twice daily plus hydroxychloroquine 400 mg once daily.

Overall, 90 of 128 patients in the infliximab group and 74 of 130 in the triple-therapy group continued the protocol until the 21-month follow-up. Patients in the infliximab group had a significantly lower area under the curve for visual analog scale for pain, most of which was accounted for during months 9-21. The percentage of patients in the infliximab group with unacceptable pain also dropped significantly from 57% at randomization to 32% at 21 months, while no difference was seen for triple therapy patients, of whom 45% had unacceptable pain at 21 months.

While patients in the infliximab group had a significantly lower risk of unacceptable pain without inflammatory control at 21 months, neither treatment arm showed a within-group difference in refractory pain from randomization to the 21-month follow-up.

Nearly one-third of patients overall still reported unacceptable pain 21 months after addition of either infliximab or sulfasalazine plus hydroxychloroquine. And at that time point, refractory pain constituted 82% of all unacceptable pain. “Notably, this pattern – with a domination of refractory pain – was evident already 3 months after starting combination therapy,” Dr. Olofsson and colleagues wrote.

The original SWEFOT study was supported in part by a grant from the Swedish Rheumatism Association, and in part by an annual unrestricted grant from Schering-Plough Sweden (now Merck Sharp & Dohme). The post hoc analysis was supported by Lund University and the Kockska Foundation, the Swedish Research Council, and the Stockholm County Council. Two authors disclosed financial relationships with multiple pharmaceutical companies.

jevans@mdedge.com

SOURCE: Olofsson T et al. Arthritis Care Res. 2020 May 20. doi: 10.1002/acr.24264.

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.

bjancin@mdedge.com

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.

bjancin@mdedge.com

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.

bjancin@mdedge.com

Mental illnesses are associated with a significantly increased risk of subsequent physical diseases, new research shows.

An international team of researchers has created an “atlas” that maps the relationship between specific mental disorders and the risk of subsequent physical illnesses.

The researchers found that, following the diagnosis of a mental disorder, psychiatric patients are significantly more likely than the general population to develop potentially life-threatening conditions, including heart disease and stroke.

These findings, the investigators noted, highlight the need for better medical care in this vulnerable population. They have created a website with detailed information about the risks of specific physical ailments and the link to particular mental disorders.

“We found that women with anxiety disorders have a 50% increased risk of developing a heart condition or stroke – over 15 years, one in three women with anxiety disorders will develop these medical disorders,” lead investigator John McGrath, MD, PhD, University of Queensland’s Brain Institute, Brisbane, Australia, and Aarhus (Denmark) University, said in a statement.

“We also looked at men with substance use disorders such as alcohol-related disorders and found they have a 400% increased risk of gut or liver disorders, while over 15 years, one in five of them will develop gut or liver conditions,” he added.

The study was published in the New England Journal of Medicine.
 

New ‘atlas’

It’s well known that patients with mental disorders have decreased quality of life, increased health care utilization, and a shorter life expectancy than individuals in the general population – about 10 years for men and 7 years for women.

However, the investigators noted, previous research examining the relationship between mental disorders and medical conditions only focused on “particular pairs or a small set of mental disorders and medical conditions.”

“We needed a comprehensive study to map the links between different types of mental disorders versus different types of general medical conditions. Our study has provided this atlas,” Dr. McGrath said in an interview.

The clinical utility of such a map could provide comprehensive data on relative and absolute risks of various medical conditions after a diagnosis of a mental disorder. This information, the researchers noted, would “help clinicians and health care planners identify the primary prevention needs of their patients.”

The study included 5.9 million people born in Denmark between 1900 and 2015 and followed them from 2000 to 2016, a total of 83.9 million person-years. The researchers followed patients for up to 17 years (2000-2016) for medical diagnoses and up to 48 years (1969-2016) for diagnoses of mental disorders.

The study’s large sample size allowed investigators to assess 10 broad types of mental disorders and 9 broad categories of medical conditions that encompassed 31 specific conditions.

Categories of medical conditions included circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, neurologic, and cancer. Mental disorder categories included organic disorders such as Alzheimer’s, substance abuse disorders, schizophrenia, mood disorders, neurotic disorders, eating disorders, personality disorders, developmental disorders, behavioral/emotional disorders, and intellectual disabilities.

The researchers estimated associations between 90 pairs of mental disorders and broad-category medical conditions, as well as 310 pairs of mental disorders and specific medical conditions.
 

‘Curious’ finding

Individuals with mental disorders showed a higher risk of medical conditions in 76 out of 90 specific mental disorder–medical condition pairs.

After adjusting for sex, age, calendar time, and previous coexisting mental disorders, the median hazard ratio for a subsequent medical condition was 1.37 in patients with a mental disorder.

The lowest HR was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval, 0.80-0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11-4.22). On the other hand, schizophrenia was associated with a reduced risk of developing musculoskeletal conditions (HR, 0.87; 95% CI, 0.84-0.91).

Dr. McGrath described this finding as “curious” and speculated it “may be related to underlying genetic risk factors.”

One of the highest cumulative associations was for mood disorders and circulatory conditions during the first 15 years following a mood disorder diagnosis, compared with the matched reference group without a mood disorder (40.9% vs. 32.6%, respectively).

The risk of developing subsequent medical conditions after a mental disorder diagnosis did not remain steady over time. For instance, although mood disorders were associated with an increased risk of developing circulatory problems (HR, 1.32; 95% CI, 1.31-1.34), the highest risk occurred during the first 6 months following diagnosis and gradually decreased over the next 15 years (HR, 2.39; 95% CI, 2.29-2.48 and HR, 1.18; 95% CI, 1.17-1.20, respectively).

“Many people with mental disorders have unhealthy lifestyle, including low exercise, poor diet, smoking, and alcohol, which may account for the increased risk of physical illness, and also they may not seek and/or may not get quick treatment for their health conditions,” said Dr. McGrath.

Additionally, “perhaps some genetic and early life exposures, such as trauma, may increase the risk of both medical conditions and mental disorders,” he added. “We need better treatments for mental disorders, so that they do not slip into unemployment or poverty.”
 

A strong case

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto and head of the mood disorders psychopharmacology unit, University Health Network, said that the research “really makes a strong case for the fact that persons who have mental disorders are at higher risk of chronic diseases, and it’s the chronic diseases that decrease their lifespan.”

Dr. McIntyre, who is also director of the Depression and Bipolar Support Alliance, said that the “takeaway message is that mental disorders are not just brain disorders but are multisystem disorders.”

For this reason, “the most appropriate way to provide care would be to provide a holistic approach to treat and prevent the chronic diseases that lead to increase in mortality,” recommended Dr. McIntyre, who was not involved with the current study.

The study was supported by grants from the Danish National Research Foundation, the National Health and Medical Research Council, the Novo Nordisk Foundation , the European Union’s Horizon 2020 Research and Innovation Program, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the European Commission, Helsefonden, the Danish Council for Independent Research, the Independent Research Fund Denmark, the National Health and Medical Research Council of Australia, and the National Institute on Drug Abuse.

Dr. McGrath has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reports receiving grants from Stanley Medical Research Institute; the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation; and receiving speaking/consultation fees from Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, and Minerva.

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

Mental illnesses are associated with a significantly increased risk of subsequent physical diseases, new research shows.

An international team of researchers has created an “atlas” that maps the relationship between specific mental disorders and the risk of subsequent physical illnesses.

The researchers found that, following the diagnosis of a mental disorder, psychiatric patients are significantly more likely than the general population to develop potentially life-threatening conditions, including heart disease and stroke.

These findings, the investigators noted, highlight the need for better medical care in this vulnerable population. They have created a website with detailed information about the risks of specific physical ailments and the link to particular mental disorders.

“We found that women with anxiety disorders have a 50% increased risk of developing a heart condition or stroke – over 15 years, one in three women with anxiety disorders will develop these medical disorders,” lead investigator John McGrath, MD, PhD, University of Queensland’s Brain Institute, Brisbane, Australia, and Aarhus (Denmark) University, said in a statement.

“We also looked at men with substance use disorders such as alcohol-related disorders and found they have a 400% increased risk of gut or liver disorders, while over 15 years, one in five of them will develop gut or liver conditions,” he added.

The study was published in the New England Journal of Medicine.
 

New ‘atlas’

It’s well known that patients with mental disorders have decreased quality of life, increased health care utilization, and a shorter life expectancy than individuals in the general population – about 10 years for men and 7 years for women.

However, the investigators noted, previous research examining the relationship between mental disorders and medical conditions only focused on “particular pairs or a small set of mental disorders and medical conditions.”

“We needed a comprehensive study to map the links between different types of mental disorders versus different types of general medical conditions. Our study has provided this atlas,” Dr. McGrath said in an interview.

The clinical utility of such a map could provide comprehensive data on relative and absolute risks of various medical conditions after a diagnosis of a mental disorder. This information, the researchers noted, would “help clinicians and health care planners identify the primary prevention needs of their patients.”

The study included 5.9 million people born in Denmark between 1900 and 2015 and followed them from 2000 to 2016, a total of 83.9 million person-years. The researchers followed patients for up to 17 years (2000-2016) for medical diagnoses and up to 48 years (1969-2016) for diagnoses of mental disorders.

The study’s large sample size allowed investigators to assess 10 broad types of mental disorders and 9 broad categories of medical conditions that encompassed 31 specific conditions.

Categories of medical conditions included circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, neurologic, and cancer. Mental disorder categories included organic disorders such as Alzheimer’s, substance abuse disorders, schizophrenia, mood disorders, neurotic disorders, eating disorders, personality disorders, developmental disorders, behavioral/emotional disorders, and intellectual disabilities.

The researchers estimated associations between 90 pairs of mental disorders and broad-category medical conditions, as well as 310 pairs of mental disorders and specific medical conditions.
 

‘Curious’ finding

Individuals with mental disorders showed a higher risk of medical conditions in 76 out of 90 specific mental disorder–medical condition pairs.

After adjusting for sex, age, calendar time, and previous coexisting mental disorders, the median hazard ratio for a subsequent medical condition was 1.37 in patients with a mental disorder.

The lowest HR was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval, 0.80-0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11-4.22). On the other hand, schizophrenia was associated with a reduced risk of developing musculoskeletal conditions (HR, 0.87; 95% CI, 0.84-0.91).

Dr. McGrath described this finding as “curious” and speculated it “may be related to underlying genetic risk factors.”

One of the highest cumulative associations was for mood disorders and circulatory conditions during the first 15 years following a mood disorder diagnosis, compared with the matched reference group without a mood disorder (40.9% vs. 32.6%, respectively).

The risk of developing subsequent medical conditions after a mental disorder diagnosis did not remain steady over time. For instance, although mood disorders were associated with an increased risk of developing circulatory problems (HR, 1.32; 95% CI, 1.31-1.34), the highest risk occurred during the first 6 months following diagnosis and gradually decreased over the next 15 years (HR, 2.39; 95% CI, 2.29-2.48 and HR, 1.18; 95% CI, 1.17-1.20, respectively).

“Many people with mental disorders have unhealthy lifestyle, including low exercise, poor diet, smoking, and alcohol, which may account for the increased risk of physical illness, and also they may not seek and/or may not get quick treatment for their health conditions,” said Dr. McGrath.

Additionally, “perhaps some genetic and early life exposures, such as trauma, may increase the risk of both medical conditions and mental disorders,” he added. “We need better treatments for mental disorders, so that they do not slip into unemployment or poverty.”
 

A strong case

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto and head of the mood disorders psychopharmacology unit, University Health Network, said that the research “really makes a strong case for the fact that persons who have mental disorders are at higher risk of chronic diseases, and it’s the chronic diseases that decrease their lifespan.”

Dr. McIntyre, who is also director of the Depression and Bipolar Support Alliance, said that the “takeaway message is that mental disorders are not just brain disorders but are multisystem disorders.”

For this reason, “the most appropriate way to provide care would be to provide a holistic approach to treat and prevent the chronic diseases that lead to increase in mortality,” recommended Dr. McIntyre, who was not involved with the current study.

The study was supported by grants from the Danish National Research Foundation, the National Health and Medical Research Council, the Novo Nordisk Foundation , the European Union’s Horizon 2020 Research and Innovation Program, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the European Commission, Helsefonden, the Danish Council for Independent Research, the Independent Research Fund Denmark, the National Health and Medical Research Council of Australia, and the National Institute on Drug Abuse.

Dr. McGrath has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reports receiving grants from Stanley Medical Research Institute; the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation; and receiving speaking/consultation fees from Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, and Minerva.

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

Mental illnesses are associated with a significantly increased risk of subsequent physical diseases, new research shows.

An international team of researchers has created an “atlas” that maps the relationship between specific mental disorders and the risk of subsequent physical illnesses.

The researchers found that, following the diagnosis of a mental disorder, psychiatric patients are significantly more likely than the general population to develop potentially life-threatening conditions, including heart disease and stroke.

These findings, the investigators noted, highlight the need for better medical care in this vulnerable population. They have created a website with detailed information about the risks of specific physical ailments and the link to particular mental disorders.

“We found that women with anxiety disorders have a 50% increased risk of developing a heart condition or stroke – over 15 years, one in three women with anxiety disorders will develop these medical disorders,” lead investigator John McGrath, MD, PhD, University of Queensland’s Brain Institute, Brisbane, Australia, and Aarhus (Denmark) University, said in a statement.

“We also looked at men with substance use disorders such as alcohol-related disorders and found they have a 400% increased risk of gut or liver disorders, while over 15 years, one in five of them will develop gut or liver conditions,” he added.

The study was published in the New England Journal of Medicine.
 

New ‘atlas’

It’s well known that patients with mental disorders have decreased quality of life, increased health care utilization, and a shorter life expectancy than individuals in the general population – about 10 years for men and 7 years for women.

However, the investigators noted, previous research examining the relationship between mental disorders and medical conditions only focused on “particular pairs or a small set of mental disorders and medical conditions.”

“We needed a comprehensive study to map the links between different types of mental disorders versus different types of general medical conditions. Our study has provided this atlas,” Dr. McGrath said in an interview.

The clinical utility of such a map could provide comprehensive data on relative and absolute risks of various medical conditions after a diagnosis of a mental disorder. This information, the researchers noted, would “help clinicians and health care planners identify the primary prevention needs of their patients.”

The study included 5.9 million people born in Denmark between 1900 and 2015 and followed them from 2000 to 2016, a total of 83.9 million person-years. The researchers followed patients for up to 17 years (2000-2016) for medical diagnoses and up to 48 years (1969-2016) for diagnoses of mental disorders.

The study’s large sample size allowed investigators to assess 10 broad types of mental disorders and 9 broad categories of medical conditions that encompassed 31 specific conditions.

Categories of medical conditions included circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, neurologic, and cancer. Mental disorder categories included organic disorders such as Alzheimer’s, substance abuse disorders, schizophrenia, mood disorders, neurotic disorders, eating disorders, personality disorders, developmental disorders, behavioral/emotional disorders, and intellectual disabilities.

The researchers estimated associations between 90 pairs of mental disorders and broad-category medical conditions, as well as 310 pairs of mental disorders and specific medical conditions.
 

‘Curious’ finding

Individuals with mental disorders showed a higher risk of medical conditions in 76 out of 90 specific mental disorder–medical condition pairs.

After adjusting for sex, age, calendar time, and previous coexisting mental disorders, the median hazard ratio for a subsequent medical condition was 1.37 in patients with a mental disorder.

The lowest HR was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval, 0.80-0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11-4.22). On the other hand, schizophrenia was associated with a reduced risk of developing musculoskeletal conditions (HR, 0.87; 95% CI, 0.84-0.91).

Dr. McGrath described this finding as “curious” and speculated it “may be related to underlying genetic risk factors.”

One of the highest cumulative associations was for mood disorders and circulatory conditions during the first 15 years following a mood disorder diagnosis, compared with the matched reference group without a mood disorder (40.9% vs. 32.6%, respectively).

The risk of developing subsequent medical conditions after a mental disorder diagnosis did not remain steady over time. For instance, although mood disorders were associated with an increased risk of developing circulatory problems (HR, 1.32; 95% CI, 1.31-1.34), the highest risk occurred during the first 6 months following diagnosis and gradually decreased over the next 15 years (HR, 2.39; 95% CI, 2.29-2.48 and HR, 1.18; 95% CI, 1.17-1.20, respectively).

“Many people with mental disorders have unhealthy lifestyle, including low exercise, poor diet, smoking, and alcohol, which may account for the increased risk of physical illness, and also they may not seek and/or may not get quick treatment for their health conditions,” said Dr. McGrath.

Additionally, “perhaps some genetic and early life exposures, such as trauma, may increase the risk of both medical conditions and mental disorders,” he added. “We need better treatments for mental disorders, so that they do not slip into unemployment or poverty.”
 

A strong case

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto and head of the mood disorders psychopharmacology unit, University Health Network, said that the research “really makes a strong case for the fact that persons who have mental disorders are at higher risk of chronic diseases, and it’s the chronic diseases that decrease their lifespan.”

Dr. McIntyre, who is also director of the Depression and Bipolar Support Alliance, said that the “takeaway message is that mental disorders are not just brain disorders but are multisystem disorders.”

For this reason, “the most appropriate way to provide care would be to provide a holistic approach to treat and prevent the chronic diseases that lead to increase in mortality,” recommended Dr. McIntyre, who was not involved with the current study.

The study was supported by grants from the Danish National Research Foundation, the National Health and Medical Research Council, the Novo Nordisk Foundation , the European Union’s Horizon 2020 Research and Innovation Program, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the European Commission, Helsefonden, the Danish Council for Independent Research, the Independent Research Fund Denmark, the National Health and Medical Research Council of Australia, and the National Institute on Drug Abuse.

Dr. McGrath has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reports receiving grants from Stanley Medical Research Institute; the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation; and receiving speaking/consultation fees from Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, and Minerva.

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.

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.