Rheumatology

Opioid use does not decline after patients with inflammatory arthritis start TNF inhibitor therapy; in fact, average use appears to increase, results from a new study show.

“Starting a TNF inhibitor, you would think the pain would go down, and we were hoping the dose of opioids would go down with it,” said investigator Olafur Palsson, MD, from the University of Iceland in Reykjavik and Lund University in Sweden.

“But this research shows that the insertion of a TNF inhibitor has only a minor effect on that,” he told Medscape Medical News.

The findings are an “important reminder” to rheumatologists that they should broaden their consideration of other pain treatments and techniques for patients with inflammatory arthritis, Dr. Palsson said. “They should focus on trying other tactics to get patients’ pain and stiffness under control; there may be some underlying factors.”

The investigators compared opioid prescription rates in 940 patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and undifferentiated arthritis with a control group of 4,700 matched subjects. Dr. Palsson presented the findings at the virtual European League Against Rheumatism (EULAR) 2020 Congress.

The team assessed nationwide databases that capture all patients taking biologics for rheumatic diseases and more than 90% of all drug prescriptions. They found that patients with inflammatory arthritis in Iceland were more likely to have received at least one opioid prescription than control subjects (75% vs. 43%).

During the study period, average yearly opioid dose rose much more in the patient group than in the control group. And 2 years after the initiation of TNF inhibitors, the number of patients taking opioids was unchanged from baseline, at about 40%.

Overall, the patient group was prescribed nearly six times more opioids than the control group. The investigators used a bootstrapping analysis to obtain a reliable confidence interval.

“In a way, the data are extremely skewed,” Dr. Palsson explained. “Most patients were taking very low doses of opioids and a few were taking extremely high doses. It’s hard to do a statistical analysis.”

“With bootstrapping, you don’t detect small fluctuations in data,” he said, acknowledging this study limitation. Also, “prescription data don’t necessarily reflect consumption” of a drug. People prescribed high doses may not necessarily be consuming high doses.”

Additionally, the risk for addiction is low when opioids are used as intended, said John Isaacs, MBBS, PhD, from Newcastle University in Newcastle Upon Tyne, United Kingdom, who is chair of the EULAR scientific program committee.

To alleviate chronic pain, opioids “should, in any case, only be part of a comprehensive therapy program in which doctors, psychologists, and physiotherapists work together,” Dr. Isaacs said in a EULAR news release.

Dr. Palsson has disclosed no relevant financial relationships. Dr. Isaacs is a consultant or has received honoraria or grants from Pfizer, AbbVie, Amgen, Merck, Roche, and UCB.

This article first appeared on Medscape.com.



 

Opioid use does not decline after patients with inflammatory arthritis start TNF inhibitor therapy; in fact, average use appears to increase, results from a new study show.

“Starting a TNF inhibitor, you would think the pain would go down, and we were hoping the dose of opioids would go down with it,” said investigator Olafur Palsson, MD, from the University of Iceland in Reykjavik and Lund University in Sweden.

“But this research shows that the insertion of a TNF inhibitor has only a minor effect on that,” he told Medscape Medical News.

The findings are an “important reminder” to rheumatologists that they should broaden their consideration of other pain treatments and techniques for patients with inflammatory arthritis, Dr. Palsson said. “They should focus on trying other tactics to get patients’ pain and stiffness under control; there may be some underlying factors.”

The investigators compared opioid prescription rates in 940 patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and undifferentiated arthritis with a control group of 4,700 matched subjects. Dr. Palsson presented the findings at the virtual European League Against Rheumatism (EULAR) 2020 Congress.

The team assessed nationwide databases that capture all patients taking biologics for rheumatic diseases and more than 90% of all drug prescriptions. They found that patients with inflammatory arthritis in Iceland were more likely to have received at least one opioid prescription than control subjects (75% vs. 43%).

During the study period, average yearly opioid dose rose much more in the patient group than in the control group. And 2 years after the initiation of TNF inhibitors, the number of patients taking opioids was unchanged from baseline, at about 40%.

Overall, the patient group was prescribed nearly six times more opioids than the control group. The investigators used a bootstrapping analysis to obtain a reliable confidence interval.

“In a way, the data are extremely skewed,” Dr. Palsson explained. “Most patients were taking very low doses of opioids and a few were taking extremely high doses. It’s hard to do a statistical analysis.”

“With bootstrapping, you don’t detect small fluctuations in data,” he said, acknowledging this study limitation. Also, “prescription data don’t necessarily reflect consumption” of a drug. People prescribed high doses may not necessarily be consuming high doses.”

Additionally, the risk for addiction is low when opioids are used as intended, said John Isaacs, MBBS, PhD, from Newcastle University in Newcastle Upon Tyne, United Kingdom, who is chair of the EULAR scientific program committee.

To alleviate chronic pain, opioids “should, in any case, only be part of a comprehensive therapy program in which doctors, psychologists, and physiotherapists work together,” Dr. Isaacs said in a EULAR news release.

Dr. Palsson has disclosed no relevant financial relationships. Dr. Isaacs is a consultant or has received honoraria or grants from Pfizer, AbbVie, Amgen, Merck, Roche, and UCB.

This article first appeared on Medscape.com.



 

Opioid use does not decline after patients with inflammatory arthritis start TNF inhibitor therapy; in fact, average use appears to increase, results from a new study show.

“Starting a TNF inhibitor, you would think the pain would go down, and we were hoping the dose of opioids would go down with it,” said investigator Olafur Palsson, MD, from the University of Iceland in Reykjavik and Lund University in Sweden.

“But this research shows that the insertion of a TNF inhibitor has only a minor effect on that,” he told Medscape Medical News.

The findings are an “important reminder” to rheumatologists that they should broaden their consideration of other pain treatments and techniques for patients with inflammatory arthritis, Dr. Palsson said. “They should focus on trying other tactics to get patients’ pain and stiffness under control; there may be some underlying factors.”

The investigators compared opioid prescription rates in 940 patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and undifferentiated arthritis with a control group of 4,700 matched subjects. Dr. Palsson presented the findings at the virtual European League Against Rheumatism (EULAR) 2020 Congress.

The team assessed nationwide databases that capture all patients taking biologics for rheumatic diseases and more than 90% of all drug prescriptions. They found that patients with inflammatory arthritis in Iceland were more likely to have received at least one opioid prescription than control subjects (75% vs. 43%).

During the study period, average yearly opioid dose rose much more in the patient group than in the control group. And 2 years after the initiation of TNF inhibitors, the number of patients taking opioids was unchanged from baseline, at about 40%.

Overall, the patient group was prescribed nearly six times more opioids than the control group. The investigators used a bootstrapping analysis to obtain a reliable confidence interval.

“In a way, the data are extremely skewed,” Dr. Palsson explained. “Most patients were taking very low doses of opioids and a few were taking extremely high doses. It’s hard to do a statistical analysis.”

“With bootstrapping, you don’t detect small fluctuations in data,” he said, acknowledging this study limitation. Also, “prescription data don’t necessarily reflect consumption” of a drug. People prescribed high doses may not necessarily be consuming high doses.”

Additionally, the risk for addiction is low when opioids are used as intended, said John Isaacs, MBBS, PhD, from Newcastle University in Newcastle Upon Tyne, United Kingdom, who is chair of the EULAR scientific program committee.

To alleviate chronic pain, opioids “should, in any case, only be part of a comprehensive therapy program in which doctors, psychologists, and physiotherapists work together,” Dr. Isaacs said in a EULAR news release.

Dr. Palsson has disclosed no relevant financial relationships. Dr. Isaacs is a consultant or has received honoraria or grants from Pfizer, AbbVie, Amgen, Merck, Roche, and UCB.

This article first appeared on Medscape.com.



 

The risk for venous thromboembolism is almost 50% lower in patients with RA taking TNF inhibitors than in those taking conventional synthetic disease-modifying antirheumatic drugs (DMARDs), according to data from the German RABBIT registry.

“Some rheumatologists have thought TNF inhibitors could increase the risk for venous thromboembolism events, but we don’t think this is true, based on our findings,” said investigator Anja Strangfeld, MD, PhD, from the German Rheumatism Research Center in Berlin.

The risk is more than one-third lower in RA patients treated with other newer biologics, such as abatacept, rituximab, sarilumab, and tocilizumab.

However, risk for a serious venous thromboembolism is twice as high in patients with C-reactive protein (CRP) levels above 5 mg/L and is nearly three times as high in patients 65 years and older.

For the study, Dr. Strangfeld and her colleagues followed about 11,000 patients for more than 10 years. The findings were presented at the European League Against Rheumatism (EULAR) 2020 Congress.

“Patients with RA have a greater risk for venous thromboembolism compared with the general population, but we didn’t know the risk conveyed by different DMARD treatments,” Dr. Strangfeld told Medscape Medical News. “It is also evident that higher age and lower capacity for physical function increase the risk, which was not so surprising.”

Chronic inflammation in RA patients elevates the risk for deep vein and pulmonary thrombosis by two to three times, said John Isaacs, MBBS, PhD, from Newcastle University in Newcastle Upon Tyne, United Kingdom, who is chair of the EULAR scientific program committee.

Among the supporting studies Dr. Isaacs discussed during an online press conference was a Swedish trial of more than 46,000 RA patients, which had been presented earlier by Viktor Molander, a PhD candidate from the Karolinska Institute in Stockholm (abstract OP0034).

Mr. Molander’s team showed that one in 100 patients with high disease activity will develop venous thromboembolism within a year, which is twice the number of events seen among patients in remission.

Combined with the RABBIT data, both studies “show if you can control their disease in the right way, you’re not only helping rheumatoid arthritis patients feel better, but you could be prolonging their lives,” Dr. Isaacs said.

The prospective RABBIT study followed RA patients who began receiving a new DMARD after treatment failed with at least one conventional synthetic DMARD, such as methotrexate or leflunomide. At baseline, those taking TNF inhibitors or other biologics had higher CRP levels on average, as well as a higher rate of existing cardiovascular disease. They also received glucocorticoids, such as prednisone, more often.

The observational nature of the RABBIT study is a weakness, Dr. Strangfeld said, and it could not prove cause and effect. But the methodology had several strengths, including input on patient factors from participating rheumatologists at least every 6 months.

“We enrolled patients at the start of treatment and observed them, regardless of any treatment changes, for up to 10 years,” she added. “That’s a really long observation period.”

The RABBIT data can help shape treatment decisions, said Loreto Carmona, MD, PhD, from the Musculoskeletal Health Institute in Madrid, who is chair of the EULAR abstract selection committee.

For a woman with RA who smokes and takes oral contraceptives, for example, “if she has high levels of inflammation, I think it’s okay to use TNF inhibitors, where maybe in the past we wouldn’t have thought that,” she said.

“The TNF inhibitors are actually reducing the inflammation and, therefore, reducing the risk,” Dr. Carmona told Medscape Medical News. “It could be an effect of using the drugs on people with higher levels of inflammation. It’s an indirect protective effect.”

The study was funded by a joint unconditional grant from AbbVie, Amgen, BMS, Fresenius-Kabi, Hexal, Lilly, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. Dr. Strangfeld is on the speakers bureau of AbbVie, BMS, Pfizer, Roche and Sanofi-Aventis. Dr. Isaacs is a consultant or has received honoraria or grants from Pfizer, AbbVie, Amgen, Merck, Roche, and UCB. Dr. Carmona has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.




 

The risk for venous thromboembolism is almost 50% lower in patients with RA taking TNF inhibitors than in those taking conventional synthetic disease-modifying antirheumatic drugs (DMARDs), according to data from the German RABBIT registry.

“Some rheumatologists have thought TNF inhibitors could increase the risk for venous thromboembolism events, but we don’t think this is true, based on our findings,” said investigator Anja Strangfeld, MD, PhD, from the German Rheumatism Research Center in Berlin.

The risk is more than one-third lower in RA patients treated with other newer biologics, such as abatacept, rituximab, sarilumab, and tocilizumab.

However, risk for a serious venous thromboembolism is twice as high in patients with C-reactive protein (CRP) levels above 5 mg/L and is nearly three times as high in patients 65 years and older.

For the study, Dr. Strangfeld and her colleagues followed about 11,000 patients for more than 10 years. The findings were presented at the European League Against Rheumatism (EULAR) 2020 Congress.

“Patients with RA have a greater risk for venous thromboembolism compared with the general population, but we didn’t know the risk conveyed by different DMARD treatments,” Dr. Strangfeld told Medscape Medical News. “It is also evident that higher age and lower capacity for physical function increase the risk, which was not so surprising.”

Chronic inflammation in RA patients elevates the risk for deep vein and pulmonary thrombosis by two to three times, said John Isaacs, MBBS, PhD, from Newcastle University in Newcastle Upon Tyne, United Kingdom, who is chair of the EULAR scientific program committee.

Among the supporting studies Dr. Isaacs discussed during an online press conference was a Swedish trial of more than 46,000 RA patients, which had been presented earlier by Viktor Molander, a PhD candidate from the Karolinska Institute in Stockholm (abstract OP0034).

Mr. Molander’s team showed that one in 100 patients with high disease activity will develop venous thromboembolism within a year, which is twice the number of events seen among patients in remission.

Combined with the RABBIT data, both studies “show if you can control their disease in the right way, you’re not only helping rheumatoid arthritis patients feel better, but you could be prolonging their lives,” Dr. Isaacs said.

The prospective RABBIT study followed RA patients who began receiving a new DMARD after treatment failed with at least one conventional synthetic DMARD, such as methotrexate or leflunomide. At baseline, those taking TNF inhibitors or other biologics had higher CRP levels on average, as well as a higher rate of existing cardiovascular disease. They also received glucocorticoids, such as prednisone, more often.

The observational nature of the RABBIT study is a weakness, Dr. Strangfeld said, and it could not prove cause and effect. But the methodology had several strengths, including input on patient factors from participating rheumatologists at least every 6 months.

“We enrolled patients at the start of treatment and observed them, regardless of any treatment changes, for up to 10 years,” she added. “That’s a really long observation period.”

The RABBIT data can help shape treatment decisions, said Loreto Carmona, MD, PhD, from the Musculoskeletal Health Institute in Madrid, who is chair of the EULAR abstract selection committee.

For a woman with RA who smokes and takes oral contraceptives, for example, “if she has high levels of inflammation, I think it’s okay to use TNF inhibitors, where maybe in the past we wouldn’t have thought that,” she said.

“The TNF inhibitors are actually reducing the inflammation and, therefore, reducing the risk,” Dr. Carmona told Medscape Medical News. “It could be an effect of using the drugs on people with higher levels of inflammation. It’s an indirect protective effect.”

The study was funded by a joint unconditional grant from AbbVie, Amgen, BMS, Fresenius-Kabi, Hexal, Lilly, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. Dr. Strangfeld is on the speakers bureau of AbbVie, BMS, Pfizer, Roche and Sanofi-Aventis. Dr. Isaacs is a consultant or has received honoraria or grants from Pfizer, AbbVie, Amgen, Merck, Roche, and UCB. Dr. Carmona has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.




 

The risk for venous thromboembolism is almost 50% lower in patients with RA taking TNF inhibitors than in those taking conventional synthetic disease-modifying antirheumatic drugs (DMARDs), according to data from the German RABBIT registry.

“Some rheumatologists have thought TNF inhibitors could increase the risk for venous thromboembolism events, but we don’t think this is true, based on our findings,” said investigator Anja Strangfeld, MD, PhD, from the German Rheumatism Research Center in Berlin.

The risk is more than one-third lower in RA patients treated with other newer biologics, such as abatacept, rituximab, sarilumab, and tocilizumab.

However, risk for a serious venous thromboembolism is twice as high in patients with C-reactive protein (CRP) levels above 5 mg/L and is nearly three times as high in patients 65 years and older.

For the study, Dr. Strangfeld and her colleagues followed about 11,000 patients for more than 10 years. The findings were presented at the European League Against Rheumatism (EULAR) 2020 Congress.

“Patients with RA have a greater risk for venous thromboembolism compared with the general population, but we didn’t know the risk conveyed by different DMARD treatments,” Dr. Strangfeld told Medscape Medical News. “It is also evident that higher age and lower capacity for physical function increase the risk, which was not so surprising.”

Chronic inflammation in RA patients elevates the risk for deep vein and pulmonary thrombosis by two to three times, said John Isaacs, MBBS, PhD, from Newcastle University in Newcastle Upon Tyne, United Kingdom, who is chair of the EULAR scientific program committee.

Among the supporting studies Dr. Isaacs discussed during an online press conference was a Swedish trial of more than 46,000 RA patients, which had been presented earlier by Viktor Molander, a PhD candidate from the Karolinska Institute in Stockholm (abstract OP0034).

Mr. Molander’s team showed that one in 100 patients with high disease activity will develop venous thromboembolism within a year, which is twice the number of events seen among patients in remission.

Combined with the RABBIT data, both studies “show if you can control their disease in the right way, you’re not only helping rheumatoid arthritis patients feel better, but you could be prolonging their lives,” Dr. Isaacs said.

The prospective RABBIT study followed RA patients who began receiving a new DMARD after treatment failed with at least one conventional synthetic DMARD, such as methotrexate or leflunomide. At baseline, those taking TNF inhibitors or other biologics had higher CRP levels on average, as well as a higher rate of existing cardiovascular disease. They also received glucocorticoids, such as prednisone, more often.

The observational nature of the RABBIT study is a weakness, Dr. Strangfeld said, and it could not prove cause and effect. But the methodology had several strengths, including input on patient factors from participating rheumatologists at least every 6 months.

“We enrolled patients at the start of treatment and observed them, regardless of any treatment changes, for up to 10 years,” she added. “That’s a really long observation period.”

The RABBIT data can help shape treatment decisions, said Loreto Carmona, MD, PhD, from the Musculoskeletal Health Institute in Madrid, who is chair of the EULAR abstract selection committee.

For a woman with RA who smokes and takes oral contraceptives, for example, “if she has high levels of inflammation, I think it’s okay to use TNF inhibitors, where maybe in the past we wouldn’t have thought that,” she said.

“The TNF inhibitors are actually reducing the inflammation and, therefore, reducing the risk,” Dr. Carmona told Medscape Medical News. “It could be an effect of using the drugs on people with higher levels of inflammation. It’s an indirect protective effect.”

The study was funded by a joint unconditional grant from AbbVie, Amgen, BMS, Fresenius-Kabi, Hexal, Lilly, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. Dr. Strangfeld is on the speakers bureau of AbbVie, BMS, Pfizer, Roche and Sanofi-Aventis. Dr. Isaacs is a consultant or has received honoraria or grants from Pfizer, AbbVie, Amgen, Merck, Roche, and UCB. Dr. Carmona has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.




 

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.

The risk of melanoma was increased among patients taking biologics for immune-mediated inflammatory diseases, compared with biologic-naive patients on conventional systemic therapy, but the association was not statistically significant in a systematic review and meta-analysis published in JAMA Dermatology.

The studies included in the analysis, however, had limitations, including a lack of those comparing biologic and conventional systemic therapy in psoriasis and inflammatory bowel disease (IBD), according to Shamarke Esse, MRes, of the division of musculoskeletal and dermatological sciences at the University of Manchester (England) and colleagues. “We advocate for more large, well-designed studies of this issue to be performed to help improve certainty” regarding this association, they wrote.

Previous studies that have found an increased risk of melanoma in patients on biologics for psoriasis, rheumatoid arthritis, and IBD have “typically used the general population as the comparator,” they noted. There is a large amount of evidence that has established short-term efficacy and safety of biologics, compared with conventional systemic treatments, but concerns about longer-term cancer risk associated with biologics remains a concern. Moreover, they added, “melanoma is a highly immunogenic skin cancer and therefore of concern to patients treated with TNFIs [tumor necrosis factor inhibitors] because melanoma risk increases with suppression of the immune system and TNF-alpha plays an important role in the immune surveillance of tumors.12,13

In their review, the researchers identified seven cohort studies from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases published between January 1995 and February 2019 that evaluated melanoma risk in about 34,000 patients receiving biologics and 135,370 patients who had never been treated with biologics, and were receiving conventional systemic therapy for psoriasis, RA, or IBD. Of these, four studies were in patients with RA, two studies were in patients with IBD, and a single study was in patients with psoriasis. Six studies examined patients taking TNF inhibitors, but only one of six studies had information on specific TNF inhibitors (adalimumab, etanercept, and infliximab) in patients with RA. One study evaluated abatacept and rituximab in RA patients.

The researchers analyzed the pooled relative risk across all studies. Compared with patients who received conventional systemic therapy, there was a nonsignificant association with risk of melanoma in patients with psoriasis (hazard ratio, 1.57; 95% confidence interval, 0.61-4.09), RA (pooled relative risk, 1.20; 95% CI, 0.83-1.74), and IBD (pRR, 1.20; 95% CI, 0.60-2.40).

Among RA patients who received TNF inhibitors only, there was a slightly elevated nonsignificant risk of melanoma (pRR, 1.08; 95% CI, 0.81-1.43). Patients receiving rituximab had a pRR of 0.73 (95% CI, 0.38-1.39), and patients taking abatacept had a pRR of 1.43 (95% CI, 0.66-3.09), compared with RA patients receiving conventional systemic therapy. When excluding two major studies in the RA subgroup of patients in a sensitivity analysis, pooled risk estimates varied from 0.91 (95% CI, 0.69-1.18) to 1.95 (95% CI, 1.16- 3.30). There were no significant between-study heterogeneity or publication bias among the IBD and RA studies.

Mr. Esse and colleagues acknowledged the small number of IBD and psoriasis studies in the meta-analysis, which could affect pooled risk estimates. “Any future update of our study through the inclusion of newly published studies may produce significantly different pooled risk estimates than those reported in our meta-analysis,” they said. In addition, the use of health insurance databases, lack of risk factors for melanoma, and inconsistent information about treatment duration for patients receiving conventional systemic therapy were also limitations.

“Prospective cohort studies using an active comparator, new-user study design providing detailed information on treatment history, concomitant treatments, biologic and conventional systemic treatment duration, recreational and treatment-related UV exposure, skin color, and date of melanoma diagnosis are required to help improve certainty. These studies would also need to account for key risk factors and the latency period of melanoma,” the researchers said.

Mr. Esse disclosed being funded by a PhD studentship from the Psoriasis Association. One author disclosed receiving personal fees from Janssen, LEO Pharma, Lilly, and Novartis outside the study; another disclosed receiving grants and personal fees from those and several other pharmaceutical companies during the study, and personal fees from several pharmaceutical companies outside of the submitted work; the fourth author had no disclosures.

SOURCE: Esse S et al. JAMA Dermatol. 2020 May 20;e201300.

The risk of melanoma was increased among patients taking biologics for immune-mediated inflammatory diseases, compared with biologic-naive patients on conventional systemic therapy, but the association was not statistically significant in a systematic review and meta-analysis published in JAMA Dermatology.

The studies included in the analysis, however, had limitations, including a lack of those comparing biologic and conventional systemic therapy in psoriasis and inflammatory bowel disease (IBD), according to Shamarke Esse, MRes, of the division of musculoskeletal and dermatological sciences at the University of Manchester (England) and colleagues. “We advocate for more large, well-designed studies of this issue to be performed to help improve certainty” regarding this association, they wrote.

Previous studies that have found an increased risk of melanoma in patients on biologics for psoriasis, rheumatoid arthritis, and IBD have “typically used the general population as the comparator,” they noted. There is a large amount of evidence that has established short-term efficacy and safety of biologics, compared with conventional systemic treatments, but concerns about longer-term cancer risk associated with biologics remains a concern. Moreover, they added, “melanoma is a highly immunogenic skin cancer and therefore of concern to patients treated with TNFIs [tumor necrosis factor inhibitors] because melanoma risk increases with suppression of the immune system and TNF-alpha plays an important role in the immune surveillance of tumors.12,13

In their review, the researchers identified seven cohort studies from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases published between January 1995 and February 2019 that evaluated melanoma risk in about 34,000 patients receiving biologics and 135,370 patients who had never been treated with biologics, and were receiving conventional systemic therapy for psoriasis, RA, or IBD. Of these, four studies were in patients with RA, two studies were in patients with IBD, and a single study was in patients with psoriasis. Six studies examined patients taking TNF inhibitors, but only one of six studies had information on specific TNF inhibitors (adalimumab, etanercept, and infliximab) in patients with RA. One study evaluated abatacept and rituximab in RA patients.

The researchers analyzed the pooled relative risk across all studies. Compared with patients who received conventional systemic therapy, there was a nonsignificant association with risk of melanoma in patients with psoriasis (hazard ratio, 1.57; 95% confidence interval, 0.61-4.09), RA (pooled relative risk, 1.20; 95% CI, 0.83-1.74), and IBD (pRR, 1.20; 95% CI, 0.60-2.40).

Among RA patients who received TNF inhibitors only, there was a slightly elevated nonsignificant risk of melanoma (pRR, 1.08; 95% CI, 0.81-1.43). Patients receiving rituximab had a pRR of 0.73 (95% CI, 0.38-1.39), and patients taking abatacept had a pRR of 1.43 (95% CI, 0.66-3.09), compared with RA patients receiving conventional systemic therapy. When excluding two major studies in the RA subgroup of patients in a sensitivity analysis, pooled risk estimates varied from 0.91 (95% CI, 0.69-1.18) to 1.95 (95% CI, 1.16- 3.30). There were no significant between-study heterogeneity or publication bias among the IBD and RA studies.

Mr. Esse and colleagues acknowledged the small number of IBD and psoriasis studies in the meta-analysis, which could affect pooled risk estimates. “Any future update of our study through the inclusion of newly published studies may produce significantly different pooled risk estimates than those reported in our meta-analysis,” they said. In addition, the use of health insurance databases, lack of risk factors for melanoma, and inconsistent information about treatment duration for patients receiving conventional systemic therapy were also limitations.

“Prospective cohort studies using an active comparator, new-user study design providing detailed information on treatment history, concomitant treatments, biologic and conventional systemic treatment duration, recreational and treatment-related UV exposure, skin color, and date of melanoma diagnosis are required to help improve certainty. These studies would also need to account for key risk factors and the latency period of melanoma,” the researchers said.

Mr. Esse disclosed being funded by a PhD studentship from the Psoriasis Association. One author disclosed receiving personal fees from Janssen, LEO Pharma, Lilly, and Novartis outside the study; another disclosed receiving grants and personal fees from those and several other pharmaceutical companies during the study, and personal fees from several pharmaceutical companies outside of the submitted work; the fourth author had no disclosures.

SOURCE: Esse S et al. JAMA Dermatol. 2020 May 20;e201300.

The risk of melanoma was increased among patients taking biologics for immune-mediated inflammatory diseases, compared with biologic-naive patients on conventional systemic therapy, but the association was not statistically significant in a systematic review and meta-analysis published in JAMA Dermatology.

The studies included in the analysis, however, had limitations, including a lack of those comparing biologic and conventional systemic therapy in psoriasis and inflammatory bowel disease (IBD), according to Shamarke Esse, MRes, of the division of musculoskeletal and dermatological sciences at the University of Manchester (England) and colleagues. “We advocate for more large, well-designed studies of this issue to be performed to help improve certainty” regarding this association, they wrote.

Previous studies that have found an increased risk of melanoma in patients on biologics for psoriasis, rheumatoid arthritis, and IBD have “typically used the general population as the comparator,” they noted. There is a large amount of evidence that has established short-term efficacy and safety of biologics, compared with conventional systemic treatments, but concerns about longer-term cancer risk associated with biologics remains a concern. Moreover, they added, “melanoma is a highly immunogenic skin cancer and therefore of concern to patients treated with TNFIs [tumor necrosis factor inhibitors] because melanoma risk increases with suppression of the immune system and TNF-alpha plays an important role in the immune surveillance of tumors.12,13

In their review, the researchers identified seven cohort studies from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases published between January 1995 and February 2019 that evaluated melanoma risk in about 34,000 patients receiving biologics and 135,370 patients who had never been treated with biologics, and were receiving conventional systemic therapy for psoriasis, RA, or IBD. Of these, four studies were in patients with RA, two studies were in patients with IBD, and a single study was in patients with psoriasis. Six studies examined patients taking TNF inhibitors, but only one of six studies had information on specific TNF inhibitors (adalimumab, etanercept, and infliximab) in patients with RA. One study evaluated abatacept and rituximab in RA patients.

The researchers analyzed the pooled relative risk across all studies. Compared with patients who received conventional systemic therapy, there was a nonsignificant association with risk of melanoma in patients with psoriasis (hazard ratio, 1.57; 95% confidence interval, 0.61-4.09), RA (pooled relative risk, 1.20; 95% CI, 0.83-1.74), and IBD (pRR, 1.20; 95% CI, 0.60-2.40).

Among RA patients who received TNF inhibitors only, there was a slightly elevated nonsignificant risk of melanoma (pRR, 1.08; 95% CI, 0.81-1.43). Patients receiving rituximab had a pRR of 0.73 (95% CI, 0.38-1.39), and patients taking abatacept had a pRR of 1.43 (95% CI, 0.66-3.09), compared with RA patients receiving conventional systemic therapy. When excluding two major studies in the RA subgroup of patients in a sensitivity analysis, pooled risk estimates varied from 0.91 (95% CI, 0.69-1.18) to 1.95 (95% CI, 1.16- 3.30). There were no significant between-study heterogeneity or publication bias among the IBD and RA studies.

Mr. Esse and colleagues acknowledged the small number of IBD and psoriasis studies in the meta-analysis, which could affect pooled risk estimates. “Any future update of our study through the inclusion of newly published studies may produce significantly different pooled risk estimates than those reported in our meta-analysis,” they said. In addition, the use of health insurance databases, lack of risk factors for melanoma, and inconsistent information about treatment duration for patients receiving conventional systemic therapy were also limitations.

“Prospective cohort studies using an active comparator, new-user study design providing detailed information on treatment history, concomitant treatments, biologic and conventional systemic treatment duration, recreational and treatment-related UV exposure, skin color, and date of melanoma diagnosis are required to help improve certainty. These studies would also need to account for key risk factors and the latency period of melanoma,” the researchers said.

Mr. Esse disclosed being funded by a PhD studentship from the Psoriasis Association. One author disclosed receiving personal fees from Janssen, LEO Pharma, Lilly, and Novartis outside the study; another disclosed receiving grants and personal fees from those and several other pharmaceutical companies during the study, and personal fees from several pharmaceutical companies outside of the submitted work; the fourth author had no disclosures.

SOURCE: Esse S et al. JAMA Dermatol. 2020 May 20;e201300.

Adding a tumor necrosis factor inhibitor to the treatment regimen of patients with psoriatic arthritis who failed to reach minimal disease activity on methotrexate monotherapy after 4 or more weeks had more than triple the rate of minimal disease activity after 16 weeks, compared with patients who had their methotrexate dosage escalated but received no second drug, in a multicenter, randomized study with 245 patients.

After 16 weeks, 42% of 123 patients with psoriatic arthritis (PsA) treated with methotrexate and the tumor necrosis factor (TNF) inhibitor adalimumab achieved minimal disease activity, compared with 13% of 122 patients randomized to receive escalated methotrexate monotherapy to their maximally tolerated dosage or to a maximum of 25 mg/week, Laura C. Coates, MBChB, PhD, reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The findings are “supportive of the EULAR recommendations” for managing patients with PsA, said Dr. Coates, a rheumatologist at the University of Oxford (England). The EULAR recommendations call for starting a biologic disease-modifying antirheumatic drug (bDMARD) in patients with PsA and peripheral arthritis and “inadequate response to at least one [conventional synthetic] DMARD,” such as methotrexate (Ann Rheum Dis. 2019 Jun;79[6]:700-12). “A proportion of patients treated with methotrexate do well, but for those struggling on methotrexate, these results support use of a TNF inhibitor. It’s a balance of cost and benefit. If TNF inhibitors were as cheap as methotrexate, I suspect that would be first line more frequently,” Dr. Coates said in an interview. In contrast, the PsA management recommendations from the American College of Rheumatology make treatment with a TNF inhibitor first line, before starting with what these guidelines call an oral small molecule, the same as a conventional synthetic DMARD such as methotrexate (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

The results seen in the CONTROL study with adalimumab would likely be similar using a different TNF inhibitor or an agent that’s an adalimumab biosimilar, Dr. Coates said. The only patients with PsA and not achieving minimal disease activity on methotrexate monotherapy who should not then receive add-on treatment with a TNF inhibitor are those known to have a safety exclusion for this drug class or patients for whom the incremental cost poses a barrier, she added. In addition, patients with more substantial skin involvement may get greater benefit from a different class of bDMARD, such as a drug that inhibits interleukin-17 or IL-12 and -23 as recommended by the EULAR panel.

“We still get very good results with a TNF inhibitor for psoriasis, but in patients with severe psoriasis there is an argument to use a different drug,” Dr. Coates acknowledged. Skin responses with an IL-17 inhibitor or an IL-12/23 inhibitor “are far better” than with a TNF inhibitor, said Dr. Landewé. He also added the caution that longer-term use of adalimumab “may induce aggravation of PsA in a significant number of patients.”

CONTROL was sponsored by AbbVie, the company that markets adalimumab (Humira). Dr. Coates has been a consultant to AbbVie, as well as to Amgen, Biogen, Boehringer Ingelheim, Celgene, Jansen, Novartis, Pfizer, and UCB. Dr. Landewé has been a consultant to AbbVie, as well as to Eli Lilly, Novartis, Pfizer, and UCB.

[email protected]

SOURCE: Coates LC et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33, Abstract OP0050.

Adding a tumor necrosis factor inhibitor to the treatment regimen of patients with psoriatic arthritis who failed to reach minimal disease activity on methotrexate monotherapy after 4 or more weeks had more than triple the rate of minimal disease activity after 16 weeks, compared with patients who had their methotrexate dosage escalated but received no second drug, in a multicenter, randomized study with 245 patients.

After 16 weeks, 42% of 123 patients with psoriatic arthritis (PsA) treated with methotrexate and the tumor necrosis factor (TNF) inhibitor adalimumab achieved minimal disease activity, compared with 13% of 122 patients randomized to receive escalated methotrexate monotherapy to their maximally tolerated dosage or to a maximum of 25 mg/week, Laura C. Coates, MBChB, PhD, reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The findings are “supportive of the EULAR recommendations” for managing patients with PsA, said Dr. Coates, a rheumatologist at the University of Oxford (England). The EULAR recommendations call for starting a biologic disease-modifying antirheumatic drug (bDMARD) in patients with PsA and peripheral arthritis and “inadequate response to at least one [conventional synthetic] DMARD,” such as methotrexate (Ann Rheum Dis. 2019 Jun;79[6]:700-12). “A proportion of patients treated with methotrexate do well, but for those struggling on methotrexate, these results support use of a TNF inhibitor. It’s a balance of cost and benefit. If TNF inhibitors were as cheap as methotrexate, I suspect that would be first line more frequently,” Dr. Coates said in an interview. In contrast, the PsA management recommendations from the American College of Rheumatology make treatment with a TNF inhibitor first line, before starting with what these guidelines call an oral small molecule, the same as a conventional synthetic DMARD such as methotrexate (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

The results seen in the CONTROL study with adalimumab would likely be similar using a different TNF inhibitor or an agent that’s an adalimumab biosimilar, Dr. Coates said. The only patients with PsA and not achieving minimal disease activity on methotrexate monotherapy who should not then receive add-on treatment with a TNF inhibitor are those known to have a safety exclusion for this drug class or patients for whom the incremental cost poses a barrier, she added. In addition, patients with more substantial skin involvement may get greater benefit from a different class of bDMARD, such as a drug that inhibits interleukin-17 or IL-12 and -23 as recommended by the EULAR panel.

“We still get very good results with a TNF inhibitor for psoriasis, but in patients with severe psoriasis there is an argument to use a different drug,” Dr. Coates acknowledged. Skin responses with an IL-17 inhibitor or an IL-12/23 inhibitor “are far better” than with a TNF inhibitor, said Dr. Landewé. He also added the caution that longer-term use of adalimumab “may induce aggravation of PsA in a significant number of patients.”

CONTROL was sponsored by AbbVie, the company that markets adalimumab (Humira). Dr. Coates has been a consultant to AbbVie, as well as to Amgen, Biogen, Boehringer Ingelheim, Celgene, Jansen, Novartis, Pfizer, and UCB. Dr. Landewé has been a consultant to AbbVie, as well as to Eli Lilly, Novartis, Pfizer, and UCB.

[email protected]

SOURCE: Coates LC et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33, Abstract OP0050.

Adding a tumor necrosis factor inhibitor to the treatment regimen of patients with psoriatic arthritis who failed to reach minimal disease activity on methotrexate monotherapy after 4 or more weeks had more than triple the rate of minimal disease activity after 16 weeks, compared with patients who had their methotrexate dosage escalated but received no second drug, in a multicenter, randomized study with 245 patients.

After 16 weeks, 42% of 123 patients with psoriatic arthritis (PsA) treated with methotrexate and the tumor necrosis factor (TNF) inhibitor adalimumab achieved minimal disease activity, compared with 13% of 122 patients randomized to receive escalated methotrexate monotherapy to their maximally tolerated dosage or to a maximum of 25 mg/week, Laura C. Coates, MBChB, PhD, reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The findings are “supportive of the EULAR recommendations” for managing patients with PsA, said Dr. Coates, a rheumatologist at the University of Oxford (England). The EULAR recommendations call for starting a biologic disease-modifying antirheumatic drug (bDMARD) in patients with PsA and peripheral arthritis and “inadequate response to at least one [conventional synthetic] DMARD,” such as methotrexate (Ann Rheum Dis. 2019 Jun;79[6]:700-12). “A proportion of patients treated with methotrexate do well, but for those struggling on methotrexate, these results support use of a TNF inhibitor. It’s a balance of cost and benefit. If TNF inhibitors were as cheap as methotrexate, I suspect that would be first line more frequently,” Dr. Coates said in an interview. In contrast, the PsA management recommendations from the American College of Rheumatology make treatment with a TNF inhibitor first line, before starting with what these guidelines call an oral small molecule, the same as a conventional synthetic DMARD such as methotrexate (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

The results seen in the CONTROL study with adalimumab would likely be similar using a different TNF inhibitor or an agent that’s an adalimumab biosimilar, Dr. Coates said. The only patients with PsA and not achieving minimal disease activity on methotrexate monotherapy who should not then receive add-on treatment with a TNF inhibitor are those known to have a safety exclusion for this drug class or patients for whom the incremental cost poses a barrier, she added. In addition, patients with more substantial skin involvement may get greater benefit from a different class of bDMARD, such as a drug that inhibits interleukin-17 or IL-12 and -23 as recommended by the EULAR panel.

“We still get very good results with a TNF inhibitor for psoriasis, but in patients with severe psoriasis there is an argument to use a different drug,” Dr. Coates acknowledged. Skin responses with an IL-17 inhibitor or an IL-12/23 inhibitor “are far better” than with a TNF inhibitor, said Dr. Landewé. He also added the caution that longer-term use of adalimumab “may induce aggravation of PsA in a significant number of patients.”

CONTROL was sponsored by AbbVie, the company that markets adalimumab (Humira). Dr. Coates has been a consultant to AbbVie, as well as to Amgen, Biogen, Boehringer Ingelheim, Celgene, Jansen, Novartis, Pfizer, and UCB. Dr. Landewé has been a consultant to AbbVie, as well as to Eli Lilly, Novartis, Pfizer, and UCB.

[email protected]

SOURCE: Coates LC et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33, Abstract OP0050.

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.

Among patients with ankylosing spondylitis or undifferentiated spondyloarthritis, risk for anterior uveitis may hinge on the choice of biologic disease-modifying antirheumatic drug (bDMARD), a large Swedish cohort study suggests.

Study results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year due to COVID-19.

“Randomized, controlled trials indicate that compared to tumor necrosis factor (TNF) inhibitors, secukinumab has similar efficacy regarding axial inflammation in spondyloarthritis and better efficacy regarding cutaneous psoriasis, but is inferior in inflammatory bowel disease,” noted lead investigator Ulf Lindström, MD, PhD, of the department of rheumatology and inflammation research in the Institute of Medicine at the University of Gothenburg (Sweden). “However, the efficacy of secukinumab, compared to TNF inhibitors, in anterior uveitis has not been extensively studied.”

The investigators used national registry data to study 3,568 patients with ankylosing spondylitis or undifferentiated spondyloarthritis who started bDMARDs in 2005-2018. They considered four agents: the anti–interleukin-17A antibody secukinumab (Cosentyx) and the TNF inhibitors etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade).

Analyses based on 4,523 treatment episodes showed that after excluding the 23% of patients who had previously experienced anterior uveitis, merely 0.9% of patients experienced new-onset anterior uveitis while on their bDMARD, Dr. Lindström reported.

There was confounding by indication, whereby patients with previous anterior uveitis were channeled toward adalimumab and infliximab, and away from secukinumab and etanercept. In addition, there was confounding by line of treatment, with secukinumab usually used in the third line.

After excluding patients who had experienced anterior uveitis in the past year to partly address confounding, the adjusted risk for first on-treatment anterior uveitis was about twice as high with secukinumab and with etanercept as compared with adalimumab. After additionally excluding all biologic treatment episodes beyond the third line, elevation of risk remained significant only for etanercept.

“There is probably a higher occurrence of anterior uveitis on treatment with secukinumab, compared to adalimumab, but there may still be residual confounding and bias that we need to consider,” Dr. Lindström concluded. “As seen previously, there is a higher occurrence of anterior uveitis on etanercept compared to adalimumab or infliximab.”

Findings in context

“These results are not surprising as we have known that secukinumab and etanercept are not good for controlling recurrent and chronic uveitis,” Nigil Haroon MD, PhD, DM, commented in an interview. However, “a single episode of uveitis or infrequent episodes are not usually considered a contraindication to starting these drugs.”

Study caveats included lack of adjustment for uveitis severity and potentially missed uveitis episodes in patients who treated it themselves with steroid eyedrops, he said. “Standard practice is to keep drops with them to start at the earliest possible time point.”

“It would be useful to know the number of patients who stopped medications as a result of uveitis,” added Dr. Haroon, who is codirector of the spondylitis program at the University Health Network and associate professor of medicine and rheumatology at the University of Toronto. “Time-to-event analysis may also be interesting.”

“The study raises an important point regarding channeling bias, and this is important to consider when interpreting clinical trial data as well. Investigators are unlikely to include patients with history of uveitis (or strong family history of inflammatory bowel disease or personal history of gut symptoms) in studies with IL-17 inhibitors and etanercept. Hence, the results have to be interpreted with caution.”
 

Study details

Dr. Lindström and coinvestigators assessed incidences of any anterior uveitis (ascertained from outpatient ophthalmology visits having this diagnostic code) and of anterior uveitis flares (the subset occurring after a gap of at least 90 days without the diagnosis).

When they excluded patients who had experienced anterior uveitis in the year before starting therapy, secukinumab and etanercept carried the highest incidences of anterior uveitis (6.8 and 7.5 per 100 patient-years, respectively) and anterior uveitis flares (2.8 per 100 patient-years for each), he reported.

With adalimumab as the comparator, adjusted risk for first on-treatment anterior uveitis in this population was significantly higher with secukinumab (hazard ratio, 2.23) and etanercept (hazard ratio, 1.80).

When the investigators additionally excluded episodes of therapy beyond the third line, only etanercept carried notably higher incidences of anterior uveitis (7.0 per 100 patient-years) and anterior uveitis flares (2.6 per 100 patient-years). “This could imply that some of the higher incidence rate seen for secukinumab could be due to the fact that these patients are harder to treat and have received more biologics before,” Dr. Lindström proposed.

With adalimumab again as the comparator, the adjusted risk for first on-treatment anterior uveitis in this population was significantly higher only with etanercept (hazard ratio, 1.85).

A final analysis included all patients who started adalimumab in 2004-2018 and then switched to one of the other agents, dramatically reducing confounding by indication. In this population, the incidence rate ratio of anterior uveitis flares was 3.05 for secukinumab, 1.79 for etanercept, and 0.53 for infliximab, compared with adalimumab.

Dr. Lindström disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding. Dr. Haroon disclosed consulting for Amgen, Abbvie, Eli Lilly, Janssen, Novartis, and UCB.

SOURCE: Lindström U et al. Ann Rheum Dis. 2020;79[suppl 1]:9, Abstract OP0014.

Among patients with ankylosing spondylitis or undifferentiated spondyloarthritis, risk for anterior uveitis may hinge on the choice of biologic disease-modifying antirheumatic drug (bDMARD), a large Swedish cohort study suggests.

Study results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year due to COVID-19.

“Randomized, controlled trials indicate that compared to tumor necrosis factor (TNF) inhibitors, secukinumab has similar efficacy regarding axial inflammation in spondyloarthritis and better efficacy regarding cutaneous psoriasis, but is inferior in inflammatory bowel disease,” noted lead investigator Ulf Lindström, MD, PhD, of the department of rheumatology and inflammation research in the Institute of Medicine at the University of Gothenburg (Sweden). “However, the efficacy of secukinumab, compared to TNF inhibitors, in anterior uveitis has not been extensively studied.”

The investigators used national registry data to study 3,568 patients with ankylosing spondylitis or undifferentiated spondyloarthritis who started bDMARDs in 2005-2018. They considered four agents: the anti–interleukin-17A antibody secukinumab (Cosentyx) and the TNF inhibitors etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade).

Analyses based on 4,523 treatment episodes showed that after excluding the 23% of patients who had previously experienced anterior uveitis, merely 0.9% of patients experienced new-onset anterior uveitis while on their bDMARD, Dr. Lindström reported.

There was confounding by indication, whereby patients with previous anterior uveitis were channeled toward adalimumab and infliximab, and away from secukinumab and etanercept. In addition, there was confounding by line of treatment, with secukinumab usually used in the third line.

After excluding patients who had experienced anterior uveitis in the past year to partly address confounding, the adjusted risk for first on-treatment anterior uveitis was about twice as high with secukinumab and with etanercept as compared with adalimumab. After additionally excluding all biologic treatment episodes beyond the third line, elevation of risk remained significant only for etanercept.

“There is probably a higher occurrence of anterior uveitis on treatment with secukinumab, compared to adalimumab, but there may still be residual confounding and bias that we need to consider,” Dr. Lindström concluded. “As seen previously, there is a higher occurrence of anterior uveitis on etanercept compared to adalimumab or infliximab.”

Findings in context

“These results are not surprising as we have known that secukinumab and etanercept are not good for controlling recurrent and chronic uveitis,” Nigil Haroon MD, PhD, DM, commented in an interview. However, “a single episode of uveitis or infrequent episodes are not usually considered a contraindication to starting these drugs.”

Study caveats included lack of adjustment for uveitis severity and potentially missed uveitis episodes in patients who treated it themselves with steroid eyedrops, he said. “Standard practice is to keep drops with them to start at the earliest possible time point.”

“It would be useful to know the number of patients who stopped medications as a result of uveitis,” added Dr. Haroon, who is codirector of the spondylitis program at the University Health Network and associate professor of medicine and rheumatology at the University of Toronto. “Time-to-event analysis may also be interesting.”

“The study raises an important point regarding channeling bias, and this is important to consider when interpreting clinical trial data as well. Investigators are unlikely to include patients with history of uveitis (or strong family history of inflammatory bowel disease or personal history of gut symptoms) in studies with IL-17 inhibitors and etanercept. Hence, the results have to be interpreted with caution.”
 

Study details

Dr. Lindström and coinvestigators assessed incidences of any anterior uveitis (ascertained from outpatient ophthalmology visits having this diagnostic code) and of anterior uveitis flares (the subset occurring after a gap of at least 90 days without the diagnosis).

When they excluded patients who had experienced anterior uveitis in the year before starting therapy, secukinumab and etanercept carried the highest incidences of anterior uveitis (6.8 and 7.5 per 100 patient-years, respectively) and anterior uveitis flares (2.8 per 100 patient-years for each), he reported.

With adalimumab as the comparator, adjusted risk for first on-treatment anterior uveitis in this population was significantly higher with secukinumab (hazard ratio, 2.23) and etanercept (hazard ratio, 1.80).

When the investigators additionally excluded episodes of therapy beyond the third line, only etanercept carried notably higher incidences of anterior uveitis (7.0 per 100 patient-years) and anterior uveitis flares (2.6 per 100 patient-years). “This could imply that some of the higher incidence rate seen for secukinumab could be due to the fact that these patients are harder to treat and have received more biologics before,” Dr. Lindström proposed.

With adalimumab again as the comparator, the adjusted risk for first on-treatment anterior uveitis in this population was significantly higher only with etanercept (hazard ratio, 1.85).

A final analysis included all patients who started adalimumab in 2004-2018 and then switched to one of the other agents, dramatically reducing confounding by indication. In this population, the incidence rate ratio of anterior uveitis flares was 3.05 for secukinumab, 1.79 for etanercept, and 0.53 for infliximab, compared with adalimumab.

Dr. Lindström disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding. Dr. Haroon disclosed consulting for Amgen, Abbvie, Eli Lilly, Janssen, Novartis, and UCB.

SOURCE: Lindström U et al. Ann Rheum Dis. 2020;79[suppl 1]:9, Abstract OP0014.

Among patients with ankylosing spondylitis or undifferentiated spondyloarthritis, risk for anterior uveitis may hinge on the choice of biologic disease-modifying antirheumatic drug (bDMARD), a large Swedish cohort study suggests.

Study results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year due to COVID-19.

“Randomized, controlled trials indicate that compared to tumor necrosis factor (TNF) inhibitors, secukinumab has similar efficacy regarding axial inflammation in spondyloarthritis and better efficacy regarding cutaneous psoriasis, but is inferior in inflammatory bowel disease,” noted lead investigator Ulf Lindström, MD, PhD, of the department of rheumatology and inflammation research in the Institute of Medicine at the University of Gothenburg (Sweden). “However, the efficacy of secukinumab, compared to TNF inhibitors, in anterior uveitis has not been extensively studied.”

The investigators used national registry data to study 3,568 patients with ankylosing spondylitis or undifferentiated spondyloarthritis who started bDMARDs in 2005-2018. They considered four agents: the anti–interleukin-17A antibody secukinumab (Cosentyx) and the TNF inhibitors etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade).

Analyses based on 4,523 treatment episodes showed that after excluding the 23% of patients who had previously experienced anterior uveitis, merely 0.9% of patients experienced new-onset anterior uveitis while on their bDMARD, Dr. Lindström reported.

There was confounding by indication, whereby patients with previous anterior uveitis were channeled toward adalimumab and infliximab, and away from secukinumab and etanercept. In addition, there was confounding by line of treatment, with secukinumab usually used in the third line.

After excluding patients who had experienced anterior uveitis in the past year to partly address confounding, the adjusted risk for first on-treatment anterior uveitis was about twice as high with secukinumab and with etanercept as compared with adalimumab. After additionally excluding all biologic treatment episodes beyond the third line, elevation of risk remained significant only for etanercept.

“There is probably a higher occurrence of anterior uveitis on treatment with secukinumab, compared to adalimumab, but there may still be residual confounding and bias that we need to consider,” Dr. Lindström concluded. “As seen previously, there is a higher occurrence of anterior uveitis on etanercept compared to adalimumab or infliximab.”

Findings in context

“These results are not surprising as we have known that secukinumab and etanercept are not good for controlling recurrent and chronic uveitis,” Nigil Haroon MD, PhD, DM, commented in an interview. However, “a single episode of uveitis or infrequent episodes are not usually considered a contraindication to starting these drugs.”

Study caveats included lack of adjustment for uveitis severity and potentially missed uveitis episodes in patients who treated it themselves with steroid eyedrops, he said. “Standard practice is to keep drops with them to start at the earliest possible time point.”

“It would be useful to know the number of patients who stopped medications as a result of uveitis,” added Dr. Haroon, who is codirector of the spondylitis program at the University Health Network and associate professor of medicine and rheumatology at the University of Toronto. “Time-to-event analysis may also be interesting.”

“The study raises an important point regarding channeling bias, and this is important to consider when interpreting clinical trial data as well. Investigators are unlikely to include patients with history of uveitis (or strong family history of inflammatory bowel disease or personal history of gut symptoms) in studies with IL-17 inhibitors and etanercept. Hence, the results have to be interpreted with caution.”
 

Study details

Dr. Lindström and coinvestigators assessed incidences of any anterior uveitis (ascertained from outpatient ophthalmology visits having this diagnostic code) and of anterior uveitis flares (the subset occurring after a gap of at least 90 days without the diagnosis).

When they excluded patients who had experienced anterior uveitis in the year before starting therapy, secukinumab and etanercept carried the highest incidences of anterior uveitis (6.8 and 7.5 per 100 patient-years, respectively) and anterior uveitis flares (2.8 per 100 patient-years for each), he reported.

With adalimumab as the comparator, adjusted risk for first on-treatment anterior uveitis in this population was significantly higher with secukinumab (hazard ratio, 2.23) and etanercept (hazard ratio, 1.80).

When the investigators additionally excluded episodes of therapy beyond the third line, only etanercept carried notably higher incidences of anterior uveitis (7.0 per 100 patient-years) and anterior uveitis flares (2.6 per 100 patient-years). “This could imply that some of the higher incidence rate seen for secukinumab could be due to the fact that these patients are harder to treat and have received more biologics before,” Dr. Lindström proposed.

With adalimumab again as the comparator, the adjusted risk for first on-treatment anterior uveitis in this population was significantly higher only with etanercept (hazard ratio, 1.85).

A final analysis included all patients who started adalimumab in 2004-2018 and then switched to one of the other agents, dramatically reducing confounding by indication. In this population, the incidence rate ratio of anterior uveitis flares was 3.05 for secukinumab, 1.79 for etanercept, and 0.53 for infliximab, compared with adalimumab.

Dr. Lindström disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding. Dr. Haroon disclosed consulting for Amgen, Abbvie, Eli Lilly, Janssen, Novartis, and UCB.

SOURCE: Lindström U et al. Ann Rheum Dis. 2020;79[suppl 1]:9, Abstract OP0014.

Patients with OA treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs, according to the results of a large, population-based study performed in British Columbia.

Within 1 year of starting treatment, 296 of 13,798 patients treated with tramadol had died, compared with 246 of 13,798 treated with naproxen, giving a death rate of 21.5 versus 17.8 per 1,000 person-years, and representing a 20% increase in all-cause mortality versus the NSAID (hazard ratio, 1.2).

Similar results were seen comparing tramadol with diclofenac and tramadol with cyclooxygenase (COX)-2 inhibitors, but with increasing death rates of 24.8 versus 19.5 per 1,000 person-years (HR, 1.3) and 23.6 versus 15.7 per 1,000 person-years (HR, 1.5), respectively.

However, all-cause mortality was lower with tramadol than with the opiate painkiller, codeine (21.5 vs. 25.5 per 1,000 person-years; HR, 0.8), reported Ms. Lingyi Li, a PhD student from the University of British Columbia, Vancouver, at the annual European Congress of Rheumatology, held online this year due to COVID-19.

This is not the first time that tramadol’s excess mortality risk has been highlighted. Indeed, just last year (JAMA. 2019;321[10]:969-82), researchers using The Health Improvement Network database reported found that tramadol was associated with higher all-cause mortality than two COX-2 inhibitors, celecoxib (31.2 versus 18.4 per 1,000 person-years) and etoricoxib (25.7 versus 12.8 per 1,000 person-years).

Ms. Li and associates’ data not only now add further weight to those findings, but also go a step further by also looking at other serious risks associated with tramadol’s use among patients with OA. “The objective of this study is to compare tramadol with other commonly prescribed pain relief medications on the risk of several severe outcomes, including mortality, cardiovascular diseases [CVD], venous thromboembolism [VTE], and hip fracture,” Ms. Li said during her virtual presentation.

Using sequential propensity score matching, the researchers compared data on patients in British Columbia during 2005-2014 with a first prescription of tramadol (56,325), the NSAIDs naproxen (n = 13,798) or diclofenac (n = 17,675), COX-2 inhibitors (17,039), or codeine (n = 7,813).

“For CVD, we found that there is a higher risk among tramadol users, compared with diclofenac [HR, 1.2] and COX-2 inhibitors [HR, 1.2], but not with naproxen [HR, 1.0] and codeine [HR, 0.9] users,” Ms. Li reported.

Similarly, the 1-year risk of VTE was significantly higher among tramadol users only when compared with diclofenac (HR, 1.5) and COX-2 inhibitors (HR, 1.7).

“For hip fractures, tramadol initiation was associated with an increased risk of hip fractures, compared with all NSAIDs, but not with codeine,” Ms. Li said. The risk of hip fractures was 40%-50% higher with tramadol versus naproxen (HR, 1.4), diclofenac and COX-2 inhibitors (both HR, 1.5).

“Our results suggest an unfavorable safety profile of tramadol use,” Ms. Li said, suggesting that “several guidelines on tramadol use in clinical practice might need to be revisited.”

According to a recent Cochrane review there is “moderate-quality evidence” that tramadol “has no important benefit on mean pain or function in people with osteoarthritis.” The authors of the review wrote that, while some patients might glean a benefit from treatment, the evidence suggests that “adverse events probably cause substantially more participants to stop taking tramadol.”

Current guidance on the use of tramadol varies. The American Academy of Orthopaedic Surgeons guidelines recommend its use in patients with symptomatic knee OA on a par with NSAIDs while the American College of Rheumatology guidance (Arthritis Care Res. 2020;72[2]:149-62) conditionally recommends that it be used only if there is no real alternative, such as a contraindication to NSAIDs or pain relief is ineffective.

Patients with rheumatic disease are increasingly taking opioid painkillers such as tramadol, with other data reported at the EULAR 2020 E-Congress showing a rise from 15% in 2007 to 25% in 2016 in the Catalonia region of Spain alone. A rise from 5% to 10% has previously been reported in the United States from 2003 to 2009.

With increasing rates of tramadol prescribing, the worry is that perhaps tramadol is not as safe a people think it is, as Thomas Schwenk, MD, pointed out when he reviewed the previous research showing excess mortality with tramadol (NEJM Journal Watch, March 2019).

“The opioid agonist tramadol often is prescribed for patients with osteoarthritis pain because it is thought to be safer than opioids or nonsteroidal anti-inflammatory drugs,” he observed. Dr. Schwenk, who is dean of the University of Nevada, Reno, added that the “results [of that study] suggest that tramadol is not as safe as some people believe.”

He suggested cautious prescribing: “Tramadol might be an option for patients in whom NSAIDs are contraindicated, but it should be prescribed as judiciously as traditional opioids.”

Responsible prescribing to avoid opioid misuse in patients with rheumatic diseases was also advocated in a EULAR press release from the congress. A study from Iceland was highlighted that found patients with inflammatory arthritis frequently did not stop taking opioids after the source of their pain had gone; in fact, their use went up despite being treated with tumor necrosis factor inhibitors.

“We would like to raise awareness of a responsible approach both by the prescribers and also the patients,” said John Isaacs, PhD, of the University of Newcastle (England). “In order to alleviate chronic pain, medications should in any case only be part of a comprehensive therapy program, in which doctors, psychologists, and physiotherapists work together.”

The study authors had no conflicts of interest.

SOURCE: Li L et al. Ann Rheum Dis. 2020;79[suppl 1]:118, Abstract OP0191.

Patients with OA treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs, according to the results of a large, population-based study performed in British Columbia.

Within 1 year of starting treatment, 296 of 13,798 patients treated with tramadol had died, compared with 246 of 13,798 treated with naproxen, giving a death rate of 21.5 versus 17.8 per 1,000 person-years, and representing a 20% increase in all-cause mortality versus the NSAID (hazard ratio, 1.2).

Similar results were seen comparing tramadol with diclofenac and tramadol with cyclooxygenase (COX)-2 inhibitors, but with increasing death rates of 24.8 versus 19.5 per 1,000 person-years (HR, 1.3) and 23.6 versus 15.7 per 1,000 person-years (HR, 1.5), respectively.

However, all-cause mortality was lower with tramadol than with the opiate painkiller, codeine (21.5 vs. 25.5 per 1,000 person-years; HR, 0.8), reported Ms. Lingyi Li, a PhD student from the University of British Columbia, Vancouver, at the annual European Congress of Rheumatology, held online this year due to COVID-19.

This is not the first time that tramadol’s excess mortality risk has been highlighted. Indeed, just last year (JAMA. 2019;321[10]:969-82), researchers using The Health Improvement Network database reported found that tramadol was associated with higher all-cause mortality than two COX-2 inhibitors, celecoxib (31.2 versus 18.4 per 1,000 person-years) and etoricoxib (25.7 versus 12.8 per 1,000 person-years).

Ms. Li and associates’ data not only now add further weight to those findings, but also go a step further by also looking at other serious risks associated with tramadol’s use among patients with OA. “The objective of this study is to compare tramadol with other commonly prescribed pain relief medications on the risk of several severe outcomes, including mortality, cardiovascular diseases [CVD], venous thromboembolism [VTE], and hip fracture,” Ms. Li said during her virtual presentation.

Using sequential propensity score matching, the researchers compared data on patients in British Columbia during 2005-2014 with a first prescription of tramadol (56,325), the NSAIDs naproxen (n = 13,798) or diclofenac (n = 17,675), COX-2 inhibitors (17,039), or codeine (n = 7,813).

“For CVD, we found that there is a higher risk among tramadol users, compared with diclofenac [HR, 1.2] and COX-2 inhibitors [HR, 1.2], but not with naproxen [HR, 1.0] and codeine [HR, 0.9] users,” Ms. Li reported.

Similarly, the 1-year risk of VTE was significantly higher among tramadol users only when compared with diclofenac (HR, 1.5) and COX-2 inhibitors (HR, 1.7).

“For hip fractures, tramadol initiation was associated with an increased risk of hip fractures, compared with all NSAIDs, but not with codeine,” Ms. Li said. The risk of hip fractures was 40%-50% higher with tramadol versus naproxen (HR, 1.4), diclofenac and COX-2 inhibitors (both HR, 1.5).

“Our results suggest an unfavorable safety profile of tramadol use,” Ms. Li said, suggesting that “several guidelines on tramadol use in clinical practice might need to be revisited.”

According to a recent Cochrane review there is “moderate-quality evidence” that tramadol “has no important benefit on mean pain or function in people with osteoarthritis.” The authors of the review wrote that, while some patients might glean a benefit from treatment, the evidence suggests that “adverse events probably cause substantially more participants to stop taking tramadol.”

Current guidance on the use of tramadol varies. The American Academy of Orthopaedic Surgeons guidelines recommend its use in patients with symptomatic knee OA on a par with NSAIDs while the American College of Rheumatology guidance (Arthritis Care Res. 2020;72[2]:149-62) conditionally recommends that it be used only if there is no real alternative, such as a contraindication to NSAIDs or pain relief is ineffective.

Patients with rheumatic disease are increasingly taking opioid painkillers such as tramadol, with other data reported at the EULAR 2020 E-Congress showing a rise from 15% in 2007 to 25% in 2016 in the Catalonia region of Spain alone. A rise from 5% to 10% has previously been reported in the United States from 2003 to 2009.

With increasing rates of tramadol prescribing, the worry is that perhaps tramadol is not as safe a people think it is, as Thomas Schwenk, MD, pointed out when he reviewed the previous research showing excess mortality with tramadol (NEJM Journal Watch, March 2019).

“The opioid agonist tramadol often is prescribed for patients with osteoarthritis pain because it is thought to be safer than opioids or nonsteroidal anti-inflammatory drugs,” he observed. Dr. Schwenk, who is dean of the University of Nevada, Reno, added that the “results [of that study] suggest that tramadol is not as safe as some people believe.”

He suggested cautious prescribing: “Tramadol might be an option for patients in whom NSAIDs are contraindicated, but it should be prescribed as judiciously as traditional opioids.”

Responsible prescribing to avoid opioid misuse in patients with rheumatic diseases was also advocated in a EULAR press release from the congress. A study from Iceland was highlighted that found patients with inflammatory arthritis frequently did not stop taking opioids after the source of their pain had gone; in fact, their use went up despite being treated with tumor necrosis factor inhibitors.

“We would like to raise awareness of a responsible approach both by the prescribers and also the patients,” said John Isaacs, PhD, of the University of Newcastle (England). “In order to alleviate chronic pain, medications should in any case only be part of a comprehensive therapy program, in which doctors, psychologists, and physiotherapists work together.”

The study authors had no conflicts of interest.

SOURCE: Li L et al. Ann Rheum Dis. 2020;79[suppl 1]:118, Abstract OP0191.

Patients with OA treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs, according to the results of a large, population-based study performed in British Columbia.

Within 1 year of starting treatment, 296 of 13,798 patients treated with tramadol had died, compared with 246 of 13,798 treated with naproxen, giving a death rate of 21.5 versus 17.8 per 1,000 person-years, and representing a 20% increase in all-cause mortality versus the NSAID (hazard ratio, 1.2).

Similar results were seen comparing tramadol with diclofenac and tramadol with cyclooxygenase (COX)-2 inhibitors, but with increasing death rates of 24.8 versus 19.5 per 1,000 person-years (HR, 1.3) and 23.6 versus 15.7 per 1,000 person-years (HR, 1.5), respectively.

However, all-cause mortality was lower with tramadol than with the opiate painkiller, codeine (21.5 vs. 25.5 per 1,000 person-years; HR, 0.8), reported Ms. Lingyi Li, a PhD student from the University of British Columbia, Vancouver, at the annual European Congress of Rheumatology, held online this year due to COVID-19.

This is not the first time that tramadol’s excess mortality risk has been highlighted. Indeed, just last year (JAMA. 2019;321[10]:969-82), researchers using The Health Improvement Network database reported found that tramadol was associated with higher all-cause mortality than two COX-2 inhibitors, celecoxib (31.2 versus 18.4 per 1,000 person-years) and etoricoxib (25.7 versus 12.8 per 1,000 person-years).

Ms. Li and associates’ data not only now add further weight to those findings, but also go a step further by also looking at other serious risks associated with tramadol’s use among patients with OA. “The objective of this study is to compare tramadol with other commonly prescribed pain relief medications on the risk of several severe outcomes, including mortality, cardiovascular diseases [CVD], venous thromboembolism [VTE], and hip fracture,” Ms. Li said during her virtual presentation.

Using sequential propensity score matching, the researchers compared data on patients in British Columbia during 2005-2014 with a first prescription of tramadol (56,325), the NSAIDs naproxen (n = 13,798) or diclofenac (n = 17,675), COX-2 inhibitors (17,039), or codeine (n = 7,813).

“For CVD, we found that there is a higher risk among tramadol users, compared with diclofenac [HR, 1.2] and COX-2 inhibitors [HR, 1.2], but not with naproxen [HR, 1.0] and codeine [HR, 0.9] users,” Ms. Li reported.

Similarly, the 1-year risk of VTE was significantly higher among tramadol users only when compared with diclofenac (HR, 1.5) and COX-2 inhibitors (HR, 1.7).

“For hip fractures, tramadol initiation was associated with an increased risk of hip fractures, compared with all NSAIDs, but not with codeine,” Ms. Li said. The risk of hip fractures was 40%-50% higher with tramadol versus naproxen (HR, 1.4), diclofenac and COX-2 inhibitors (both HR, 1.5).

“Our results suggest an unfavorable safety profile of tramadol use,” Ms. Li said, suggesting that “several guidelines on tramadol use in clinical practice might need to be revisited.”

According to a recent Cochrane review there is “moderate-quality evidence” that tramadol “has no important benefit on mean pain or function in people with osteoarthritis.” The authors of the review wrote that, while some patients might glean a benefit from treatment, the evidence suggests that “adverse events probably cause substantially more participants to stop taking tramadol.”

Current guidance on the use of tramadol varies. The American Academy of Orthopaedic Surgeons guidelines recommend its use in patients with symptomatic knee OA on a par with NSAIDs while the American College of Rheumatology guidance (Arthritis Care Res. 2020;72[2]:149-62) conditionally recommends that it be used only if there is no real alternative, such as a contraindication to NSAIDs or pain relief is ineffective.

Patients with rheumatic disease are increasingly taking opioid painkillers such as tramadol, with other data reported at the EULAR 2020 E-Congress showing a rise from 15% in 2007 to 25% in 2016 in the Catalonia region of Spain alone. A rise from 5% to 10% has previously been reported in the United States from 2003 to 2009.

With increasing rates of tramadol prescribing, the worry is that perhaps tramadol is not as safe a people think it is, as Thomas Schwenk, MD, pointed out when he reviewed the previous research showing excess mortality with tramadol (NEJM Journal Watch, March 2019).

“The opioid agonist tramadol often is prescribed for patients with osteoarthritis pain because it is thought to be safer than opioids or nonsteroidal anti-inflammatory drugs,” he observed. Dr. Schwenk, who is dean of the University of Nevada, Reno, added that the “results [of that study] suggest that tramadol is not as safe as some people believe.”

He suggested cautious prescribing: “Tramadol might be an option for patients in whom NSAIDs are contraindicated, but it should be prescribed as judiciously as traditional opioids.”

Responsible prescribing to avoid opioid misuse in patients with rheumatic diseases was also advocated in a EULAR press release from the congress. A study from Iceland was highlighted that found patients with inflammatory arthritis frequently did not stop taking opioids after the source of their pain had gone; in fact, their use went up despite being treated with tumor necrosis factor inhibitors.

“We would like to raise awareness of a responsible approach both by the prescribers and also the patients,” said John Isaacs, PhD, of the University of Newcastle (England). “In order to alleviate chronic pain, medications should in any case only be part of a comprehensive therapy program, in which doctors, psychologists, and physiotherapists work together.”

The study authors had no conflicts of interest.

SOURCE: Li L et al. Ann Rheum Dis. 2020;79[suppl 1]:118, Abstract OP0191.

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.