Background/Purpose:  Several new biologic disease-modifying antirheumatic drugs (DMARDs) have been approved for treatment of rheumatoid arthritis (RA) in United States. However, their comparative risks of serious infections are unclear. The objective of the current study is to determine if the risks of hospitalized infections associated with various biologics used for RA differs.

Methods: Using Medicare data from 2006-2011 for 100% of patients with RA, we identified new biologic users of etanercept, adalimumab, certolizumab, golimumab, infliximab, abatacept, rituximab and tocilizumab.  New users were defined specific to each drug as no use of that therapy in the prior 12 month ‘baseline’ period. To increase homogeneity of patients for biologics typically not used as first line agents, patients were required to have used another biologic during baseline (i.e. they were ‘switchers’). Eligible subjects were continuously enrolled in Medicare Parts A, B and D in baseline and throughout follow up. Follow up started from the drug initiation date and ended at the earliest date of: a hospitalized infection, 12 months after biologic initiation, a 30 day gap in current exposure, death, or loss of Medicare coverage. We identified hospitalized infection using inpatient physician diagnosis codes in primary or secondary position. Confounding was controlled through a person-specific infection risk score that was separately derived among biologic-naïve new users of anti-TNF and non-biologic DMARDs. We calculated the incidence rate of hospitalized infection for each biologic and compared their hospitalized infection risks during follow-up using Cox regression adjusting for infection risk score decile, disability status, glucocorticoids use during baseline, methotrexate use during baseline, most recent biologic during baseline and Medicaid eligibility.

Results: Of 29,776 new biologic switchers, 11.9% were exposed to etanercept, 15.0% adalimumab, 5.9% certolizumab, 4.3% golimumab, 12.3% infliximab, 29.0% abatacept, 14.9% rituximab and 6.4% tocilizumab. During follow-up, we identified 2,224 hospitalized infections yielding infection incidence rates from a low of 12.3 (abatacept) to a high of 17.4 (infliximab) per 100 person years across different biologics. After adjustment for potential cofounders, etanercept, infliximab and rituximab users had significantly higher hazard ratios of hospitalized infection compared to abatacept users.  Adjusted HRs for all other drug-outcome comparisons were not significantly different from abatacept (table).

Conclusion: Among RA patients with exposure to biologic therapies, etanercept, infliximab and rituximab were associated with a higher one year risk of serious infection compared to abatacept.