Effect of Immunosuppressive or Immunomodulatory Agents on Severe COVID‐19 Outcomes: A Population‐Based Cohort Study

Abstract

Objective We estimated the association between immunosuppressive and immunomodulatory agent (IIA) exposure and severe COVID‐19 outcomes in a population‐based cohort study. Methods Participants were 18 years or older, tested positive for SARS‐CoV‐2 between February 6, 2020, and August 15, 2021, and were from administrative health data for the entire province of British Columbia, Canada. IIA use within 3 months prior to positive SARS‐CoV‐2 test included conventional disease‐modifying antirheumatic drugs (antimalarials, methotrexate, leflunomide, sulfasalazine, individually), immunosuppressants (azathioprine, mycophenolate mofetil/mycophenolate sodium [MMF], cyclophosphamide, cyclosporine, individually and collectively), tumor necrosis factor inhibitor (TNFi) biologics (adalimumab, certolizumab, etanercept, golimumab, infliximab, collectively), non‐TNFi biologics or targeted synthetic disease‐modifying antirheumatic drugs (tsDMARDs) (rituximab separately from abatacept, anakinra, secukinumab, tocilizumab, tofacitinib and ustekinumab collectively), and glucocorticoids. Severe COVID‐19 outcomes were hospitalizations for COVID‐19, ICU admissions, and deaths within 60 days of a positive test. Exposure score–overlap weighting was used to balance baseline characteristics of participants with IIA use compared with nonuse of that IIA. Logistic regression measured the association between IIA use and severe COVID‐19 outcomes. Results From 147,301 participants, we identified 515 antimalarial, 573 methotrexate, 72 leflunomide, 180 sulfasalazine, 468 immunosuppressant, 378 TNFi biologic, 49 rituximab, 144 other non‐TNFi biologic or tsDMARD, and 1348 glucocorticoid prescriptions. Risk of hospitalizations for COVID‐19 was significantly greater for MMF (odds ratio [95% CI]): 2.82 [1.81‐4.40], all immunosuppressants: 2.08 [1.51‐2.87], and glucocorticoids: 1.63 [1.36‐1.96], relative to nonuse. Similar outcomes were seen for ICU admission and MMF: 2.52 [1.34‐4.74], immunosuppressants: 2.88 [1.73‐4.78], and glucocorticoids: 1.86 [1.37‐2.54]. Only glucocorticoids use was associated with a significant increase in 60‐day mortality: 1.58 [1.21‐2.06]. No other IIAs displayed statistically significant associations with severe COVID‐19 outcomes. Conclusion Current use of MMF and glucocorticoids were associated with an increased risk of severe COVID‐19 outcomes compared with nonuse. These results emphasize the variety of circumstances of patients taking IIAs.