Risk of Herpes Zoster in Patients With Rheumatoid Arthritis Treated With Anti–TNF-α Agents
- Anja Strangfeld, MD;
- Joachim Listing, PhD;
- Peter Herzer, MD;
- Anke Liebhaber, MD;
- Karin Rockwitz, MD;
- Constanze Richter, MD;
- Angela Zink, PhD
- Author Affiliations: German Rheumatism Research Centre, Berlin (Drs Strangfeld and Listing); and German Rheumatism Research Centre and Department of Rheumatology and Clinical Immunology, Charité- University Medicine, Berlin (Dr Zink). Drs Herzer, Liebhaber, Rockwitz, and Richter are rheumatologists in private practice in Germany.
Abstract
Context The risk of bacterial infection is increased in patients treated with drugs that inhibit tumor necrosis factor α (TNF-α). Little is known about the reactivation of latent viral infections during treatment with TNF-α inhibitors.
Objective To investigate whether TNF-α inhibitors together as a class, or separately as either monoclonal anti–TNF-α antibodies (adalimumab, infliximab) or a fusion protein (etanercept), are related to higher rates of herpes zoster in patients with rheumatoid arthritis.
Design, Setting, and Patients Patients were enrolled in the German biologics register RABBIT, a prospective cohort, between May 2001 and December 2006 at the initiation of treatment with infliximab, etanercept, adalimumab, or anakinra, or when they changed conventional disease-modifying antirheumatic drug (DMARD). Treatment, clinical status, and adverse events were assessed by rheumatologists at fixed points during follow-up.
Main Outcome Measures Hazard ratio (HR) of herpes zoster episodes following anti–TNF-α treatment. Study aims were to detect a clinically significant difference (HR, 2.0) between TNF-α inhibitors as a class compared with DMARDs and to detect an HR of at least 2.5 for each of 2 types of TNF-α inhibitors, the monoclonal antibodies or the fusion protein, compared with conventional DMARDs.
Results Among 5040 patients receiving TNF-α inhibitors or conventional DMARDs, 86 episodes of herpes zoster occurred in 82 patients. Thirty-nine occurrences could be attributed to treatment with anti–TNF-α antibodies, 23 to etanercept, and 24 to conventional DMARDs. The crude incidence rate per 1000 patient-years was 11.1 (95% confidence interval [CI], 7.9-15.1) for the monoclonal antibodies, 8.9 (95% CI, 5.6-13.3) for etanercept, and 5.6 (95% CI, 3.6-8.3) for conventional DMARDs. Adjusted for age, rheumatoid arthritis severity, and glucocorticoid use, a significantly increased risk was observed for treatment with the monoclonal antibodies (HR, 1.82 [95% CI, 1.05-3.15]), although this risk was lower than the threshold for clinical significance. No significant associations were found for etanercept use (HR, 1.36 [95% CI, 0.73-2.55]) or for anti–TNF-α treatment (HR, 1.63 [95% CI, 0.97-2.74]) as a class.
Conclusion Treatment with monoclonal anti–TNF-α antibodies may be associated with increased risk of herpes zoster, but this requires further study.
