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Herpes Zoster and TNF- Antagonists

Rheumatoid arthritis patients treated with infliximab or adalimumab are at increased risk for herpes zoster.

Drugs that inhibit tumor necrosis factor (TNF-) have been shown to increase risk for serious bacterial and fungal infections. Do they also increase risk for viral infections? To answer this question, researchers in Germany analyzed data from RABBIT, an ongoing, industry-funded, nationwide prospective cohort study examining the effectiveness and long-term safety of biological agents in treating rheumatoid arthritis. Eligible patients started new treatment with the anti–TNF- monoclonal antibodies infliximab or adalimumab, the TNF-receptor fusion protein etanercept, or the interleukin-1–receptor antagonist anakinra, or changed their conventional disease-modifying antirheumatic drug (DMARD) treatment, between May 2001 and December 2006. A total of 5040 patients were included in the analyses.

From May 2001 through October 2007, 86 episodes of herpes zoster were identified among 82 patients. Fifteen episodes involved multidermatomal herpes zoster, and 4 involved herpes zoster ophthalmicus; in 12, the patients required hospitalization. Only two patients developed postherpetic neuralgia. In a multivariate analysis that controlled for age, disease severity, and glucocorticoid use, the risk for herpes zoster was significantly higher among patients who received infliximab or adalimumab than among those who changed DMARDs (hazard ratio, 1.82; 95% confidence interval, 1.05–3.15). No increase in zoster risk was seen with etanercept (HR, 1.36; 95% CI, 0.73–2.55).

Comment: The increase in zoster incidence was modest overall. However, as noted by editorialists, the incidence of severe zoster was strikingly high. Also surprising is the low incidence of postherpetic neuralgia, which was noted across the entire study population. These findings raise the issue of whether patients being considered for infliximab or adalimumab therapy should receive the zoster vaccine before initiating such treatment. However, such immunization will likely be problematic in the setting of other immunosuppressive therapy.

— Richard T. Ellison III, MD

Published in Journal Watch Infectious Diseases March 4, 2009

Citation(s):

Strangfeld A et al. Risk of herpes zoster in patients with rheumatoid arthritis treated with anti–TNF- agents. JAMA 2009 Feb 18; 301:737.

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• Medline abstract (Free)

Whitley RJ and Gnann JW Jr. Herpes zoster in the age of focused immunosuppressive therapy. JAMA 2009 Feb 18; 301:774.

• Original article (Subscription may be required)
• Medline abstract (Free)