Risk of Hospitalized Bacterial Infections Associated With Biologic Treatment Among US Veterans With Rheumatoid Arthritis
The comparative risk of infection associated with non–anti–tumor necrosis factor (anti-TNF) biologic agents is not well established. Our objective was to compare risk for hospitalized infections between anti-TNF and non–anti-TNF biologic agents in US veterans with rheumatoid arthritis (RA).
Using 1998–2011 data from the US Veterans Health Administration, we studied RA patients initiating rituximab, abatacept, or anti-TNF therapy. Exposure was based upon days supplied (injections) or usual dosing intervals (infusions). Treatment episodes were defined as new biologic agent use. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hospitalization for a bacterial infection were estimated from Cox proportional hazards models, adjusting for potential confounders.
Among 3,152 unique RA patients contributing 4,158 biologic treatment episodes to rituximab (n = 596), abatacept (n = 451), and anti-TNF agents (n = 3,111), the patient mean age was 60 years and 87% were male. The most common infections were pneumonia (37%), skin/soft tissue (22%), urinary tract (9%), and bacteremia/sepsis (7%). Hospitalized infection rates per 100 person-years were 4.4 (95% CI 3.1–6.4) for rituximab, 2.8 (95% CI 1.7–4.7) for abatacept, and 3.0 (95% CI 2.5–3.5) for anti-TNF. Compared to etanercept, the adjusted rate of hospitalized infection was not different for adalimumab (HR 1.4, 95% CI 0.9–2.2), abatacept (HR 1.1, 95% CI 0.6–2.1), or rituximab (HR 1.4, 0.8–2.6), although it was increased for infliximab (HR 2.3, 95% CI 1.3–4.0). Infection risk was greater for those taking prednisone >7.5 mg/day (HR 1.8, 95% CI 1.3–2.7) and in the highest quartile of C-reactive protein (HR 2.3, 95% CI 1.4–3.8) and erythrocyte sedimentation rate (HR 4.1, 95% CI 2.3–7.2) compared to the lowest quartile.
In older, predominantly male US veterans with RA, the risk of hospitalized bacterial infections associated with rituximab or abatacept was similar to etanercept.