The comparative risk of serious infections among rheumatoid arthritis patients starting or switching biological agents

Abstract

Background: It is unclear whether anti-tumour necrosis factor alpha and biological agents with different mechanisms of action have similar safety. This study evaluated the incidence of hospitalised infections among rheumatoid arthritis (RA) patients starting or switching various biological agents.

Methods: Using a database from a large US healthcare organisation from January 2005 to August 2009, the authors identified enrollees with RA and their treatment episodes entailing the new use of a biological agent, stratified by no biological use in the previous year ('biological-free') or switching from a different biological agent ('switchers'). Outcomes were hospitalised infections identified using previously validated algorithms. Proportional hazards models estimated the hazard ratio of hospitalised infections, comparing each biological agent with infliximab.

Results: Among 7847 biological treatment episodes, 63% were for biological-free patients and 37% for switchers. There were 364 hospitalised infections. Rates of hospitalised infection among biological-free patients and switchers were 4.6 and 7.0 per 100 person-years, respectively (p<0.0001). After multivariable adjustment controlling for biological-free/switcher status and other infection-related factors and compared with infliximab, users of abatacept (HR 0.68, 95% CI 0.48 to 0.96), adalimumab (HR 0.52, 0.39 to 0.71), etanercept (HR 0.64, 0.49 to 0.84) and rituximab (HR 0.81, 0.55 to 1.20) had lower rates of hospitalised infection. Patient risk factors contributed more to the risk of infection than did the risk associated with specific biological therapies.

Conclusion: The rate of hospitalised infections among RA patients was highest for infliximab. Most of the variability in patients' risk of infection was driven by factors other than biological agent exposure.

Figure 1

Distribution of predicted infection risk among biological-free versus switchers. The x-axis is the 1-year predicted risk of hospitalised infection, expressed as a percentage ranging from 0 to 100. The y-axis is the cumulative distribution of infection risk in the biological-free and switcher groups; the area under each of the two curves sums to 100%, representing all patients in that group. The x-axis was right-truncated at 15% to facilitate visual inspection; 97% of the biological-free patients had a predicted 1-year infection risk of 15% or less; 94% of the switcher patients had a predicted 1-year infection risk of 15% or less.

Figure 2

Adjusted* HR of hospitalised infection for biological-free, switcher and combined cohorts, compared with infliximab. *Adjusted for quintile of the infection risk score, described in the supplementary appendix (available online only).