Background/Purpose:  Several newer biologics have been approved for treatment of rheumatoid arthritis (RA) in the United States. However, their comparative risks of herpes zoster infection are not well understood. The objective of the present study is to evaluate whether the risks of herpes zoster infections associated with various biologics differ among Medicare RA population.

Methods: Using Medicare data from 2006-2011 for patients with RA, we identified new users of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, 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 characteristics to allow comparison with 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 must have been continuously enrolled in Medicare Parts A, B and D in baseline and throughout follow up and could not have had zoster medications during baseline. Follow up started from the drug initiation date and ended at the earliest date of: zoster infection, a 30 day gap in current exposure, death, loss of Medicare coverage or Dec 31, 2011. We identified herpes zoster infection using physician diagnosis code and use of antiviral medication within 7 days. 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 herpes zoster infection for each biologic and compared their herpes zoster 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 25,274 biologic switchers, 11.3% used etanercept, 15.9% adalimumab, 6.1% certolizumab, 4.4% golimumab, 12.6% infliximab, 29.0% abatacept, 14.5% rituximab and 6.3% tocilizumab. Among 24,237 patients who had no history of herpes zoster infection, we identified 336 herpes zoster infections yielding similar crude incidence rates across different biologics. After adjustment for potential cofounders and compared to infliximab users, the adjusted hazard ratios of all types of biologics were not significantly different from infliximab users. Among 1,037 patients with a history of herpes zoster infection during baseline, we identified 14 recurrent herpes zoster infections yielding an incidence rate for recurrence of 2.1 per 100 person years. We did not have enough data to look at drug-specific associations with recurrent infection.  

Conclusion: Among patients with RA, the risk for herpes zoster was similar across biologics, include those with non-TNF mechanisms of action.