Initiation of rheumatoid arthritis treatments and the risk of serious infections

Abstract

Objective. In clinical trials of RA patients on traditional DMARDs, the addition of TNF-α antagonists increased infections compared with addition of placebo. Our objective was to compare serious infections following initiation of different RA regimens. Prior comparative studies of DMARD initiation have yielded conflicting results. Methods. We estimated hospitalization rates for infections following initiation of TNF-α antagonists, other DMARDs and oral glucocorticoids in Tennessee Medicaid-enrolled RA patients (1995–2005). Exposure time was measured using pharmacy information and infections were identified using validated definitions. Initiation of RA regimens was compared using Cox regression models with MTX as the reference. Sensitivity analyses excluded glucocorticoid users, applied a first exposure carried forward approach, restricted observations to 2002–05 and first episodes of use and explored effects of unmeasured confounders. Results. We identified 28 906 new episodes of medication use, including TNF-α antagonists (8%), MTX alone (15%) and glucocorticoids alone (57%). Compared with MTX initiation, TNF-α antagonist initiation did not significantly increase the risk of hospitalizations for pneumonia [adjusted hazard ratio (aHR) 1.61; 95% CI 0.85, 3.03] or any infection (aHR 1.31; 95% CI 0.78, 2.19). Initiation of LEF, SSZ or HCQ did not increase serious infections, compared with MTX. Both initiation and concurrent glucocorticoid use were associated with a dose-dependent increase in serious infections. Sensitivity analyses showed consistent results. Conclusions. Compared with initiation of MTX alone, initiation of TNF-α antagonists was not associated with a large increase in the risk of serious infections. Glucocorticoid use was associated with a dose-dependent increase in the risk of these infections.