This study compared the incidence and hazard of ICD-9-CM-coded infections and severe infections in rheumatoid arthritis (RA) patients treated with subsequent-line (SL) BIOs (BIO) after switching from first-line (FL) anti-TNF therapy (anti-TNF).

Retrospective analysis of a large U.S. claims database. RA patients initiating an FL anti-TNF between 1/1/2004 and 3/31/2010 were identified and followed forward in time to capture all SL BIO episodes through 3/31/2010. SL BIO episodes were classified into: abatacept, adalimumab, etanercept, infliximab, or rituximab. Multivariate mixed-effects survival models compared the hazard of infections and severe infections across the SL BIO episodes with adjustment for demographic and clinical confounders.

In total, 4332 SL BIO episodes were identified: mean age 55 years; 80% female. In adjusted analyses: when compared to rituximab, the hazard of all infections was significantly higher for adalimumab (hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.09–1.55), etanercept (HR = 1.44, 95% CI = 1.20–1.72), and infliximab (HR = 1.30, 95% CI = 1.07–1.57), and insignificantly different for abatacept (HR = 1.18, 95% CI = 0.98–1.41); when compared to rituximab, the hazard of severe infection was significantly higher for infliximab (HR = 1.62, 95% CI = 1.03–2.55), and insignificantly different for abatacept (HR = 1.21, 95% CI = 0.78–1.88), adalimumab (HR = 1.10, 95% CI = 0.72–1.68), and etanercept (HR = 1.27, 95% CI = 0.83–1.95).

In RA patients treated with SL BIO, a 30–44% higher hazard of all infection was observed in anti-TNFs versus rituximab with a 62% higher hazard of severe infection observed in infliximab versus rituximab. This study used a non-randomized, observational design and is therefore subject to confounding from unmeasured factors that influence both treatment choice and infection risk.