Objective: To examine the association of methotrexate (MTX) and TNF antagonists with risk of infectious outcomes including opportunistic infections in patients with rheumatoid arthritis (RA).
Methods: RA patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry prescribed MTX, TNF antagonists or other disease modifying anti-rheumatic drugs (DMARDs) were included. The primary outcomes were incident overall and opportunistic infections. Incident rate ratios were calculated using Generalized Estimating Equation (GEE) Poisson regression models adjusted for demographics, comorbidities and RA disease activity measures.
Results: A total of 7,971 RA patients were followed. Adjusted rate of infections per 100 person-years was increased among MTX (30.9, 95% CI [29.2, 32.7]), TNF antagonist (40.1, 95% CI [37.0, 43.4]) and combination MTX/TNF antagonist users (37.1, 95% CI [34.9, 39.3]) versus other nonbiologic DMARD users (24.5, 95% CI [21.8, 27.5]). The adjusted incidence rate ratio (IRR) was increased for patients prescribed MTX (IRR 1.30, 95% CI 1.12-1.50) and TNF antagonists (IRR 1.52, 95% CI 1.30-1.78) compared to other DMARD users. For opportunistic infections, TNF antagonist use (IRR 1.67, 95% CI 0.95-2.94) was associated with increased risk. Prednisone use was associated with an increased risk of opportunistic infection (IRR 1.63, 95% CI 1.20-2.21) and an increased risk of overall infection at doses > 10 mg daily (IRR 1.30, 95% CI 1.11-1.53).
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 risk for opportunistic infections.