Objective: To examine the association of methotrexate (MTX) and tumour necrosis factor (TNF) antagonists with the risk of infectious outcomes including opportunistic infections in patients with rheumatoid arthritis (RA).
Methods: Patients with RA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry prescribed MTX, TNF antagonists or other disease-modifying antirheumatic drugs (DMARDs) were included. The primary outcomes were incident overall and opportunistic infections. Incident rate ratios were calculated using generalised estimating equation Poisson regression models adjusted for demographics, comorbidities and RA disease activity measures.
Results: A total of 7971 patients with RA were followed. The adjusted rate of infections per 100 person-years was increased among users of MTX (30.9, 95% CI 29.2 to 32.7), TNF antagonists (40.1, 95% CI 37.0 to 43.4) and a combination of MTX and TNF antagonists (37.1, 95% CI 34.9 to 39.3) compared with users of other non-biological DMARDs (24.5, 95% CI 21.8 to 27.5). The adjusted incidence rate ratio (IRR) was increased in patients treated with MTX (IRR 1.30, 95% CI 1.12 to 1.50) and TNF antagonists (IRR 1.52, 95% CI 1.30 to 1.78) compared with those treated with other DMARDs. TNF antagonist use was associated with an increased risk of opportunistic infections (IRR 1.67, 95% CI 0.95 to 2.94). Prednisone use was associated with an increased risk of opportunistic infections (IRR 1.63, 95% CI 1.20 to 2.21) and an increased risk of overall infection at doses >10 mg daily (IRR 1.30, 95% CI 1.11 to 1.53).
Conclusions: MTX, TNF antagonists and prednisone at doses >10 mg daily were associated with increased risks of overall infections. Low-dose prednisone and TNF antagonists (but not MTX) increased the risk of opportunistic infections.
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Funding JDG was supported by grant number K23AR054412 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and a Clinical Translational Research Award in Rheumatoid Arthritis from the Arthritis Foundation. This study was jointly funded by CORRONA and Genentech. Genentech authors (ET and CZ) participated in the data analysis, interpretation of data and writing of the report. No other funding sources influenced the content of this work.
Competing interests JDG has received research support from BMS, honoraria from Roche and UCB and serves as Chief Scientific Officer for CORRONA; GR has a research contract with CORRONA; JMK has received research support from Amgen, Abbott, Centocor, BMS, Roche and Genentech as well as honoraria from Abbott, Centocor, BMS, Roche and Genentech; ET was employed by Genentech Inc during this analysis; CZ is employed by Genentech Inc; WB received honoraria from Abbott, Aventis, Bayer, Elan, Merck, Ortho-McNeil, Oscient, Pfizer, Roche and Schering Plough, and research grants from Abbott, Aventis, Bayer, Merck, Pfizer and Schering Plough; MCH served as a consultant for Amgen, Bristol Meyers Squibb, Roche and UCB. AK has no competing interests.
Ethics approval The study was approved by the appropriate Institutional Review Boards of participating academic and private sites.
JDG takes responsibility for the study design; the collection, analysis and interpretation of data; the writing of the report; and the decision to submit the paper for publication.
Provenance and Peer review Not commissioned; externally peer reviewed.