Anti-tumor necrosis factor alpha ( TNF-alpha ) antibodies for the treatment of rheumatoid arthritis appears to be associated with an increased risk for herpes zoster.

There has been evidence from some studies that patients treated with anti–TNF-alpha agents are at an increased risk of bacterial infections, but little is known about the risk of viral infections, such as herpes zoster, in patients with rheumatoid arthritis receiving these types of medications.
Herpes zoster is one of the most common adverse events reported in clinical trials of anti–TNF-a agents. Patients with rheumatoid arthritis are at increased risk of herpes zoster compared with the general population.

Anja Strangfeld, of the German Rheumatism Research Center, Berlin, and colleagues investigated the association of various rheumatoid arthritis treatments, including anti–TNF-alpha therapy, with the risk of herpes zoster. The researchers analyzed data from patients who began treatment with Adalimumab ( Humira ) or Infliximab ( Remicade ) ( monoclonal anti–TNF-alpha antibodies ), Etanercept ( Enbrel ) ( a fusion protein ), the monotherapeutic agent Anakinra ( Kineret ), or when patients changed conventional disease-modifying anti-rheumatic drug ( DMARD ). Treatment, clinical status and adverse events were assessed by rheumatologists at fixed points during follow-up ( of up to three years ). A total of 5,040 patients were included in the analysis.

There were 86 cases of herpes zoster among 82 patients. Thirty-nine occurrences could be attributed to treatment with anti–TNF-alpha antibodies ( 23 to Etanercept, 24 to conventional DMARDs ). The researchers found a significant association between herpes zoster and treatment with the monoclonal anti–TNF-alpha antibodies Infliximab and Adalimumab, although this risk was lower than the threshold for clinical significance. There was no significant association between herpes zoster and treatment with Etanercept, or anti–TNF-alpha treatment as a class.

A significantly higher risk of developing herpes zoster was found for patients of older age and for treatment with glucocorticoids.

" Based on our data, we recommend careful monitoring of patients treated with monoclonal anti–TNF-alpha antibodies for early signs and symptoms of herpes zoster," the authors conclude.

In an accompanying editorial, Richard J. Whitley, and John W. Gnann Jr. of the University of Alabama at Birmingham, comment on the findings of this study.

" The TNF-alpha inhibitors provide tremendous benefit to a broad spectrum of patients with systemic inflammatory diseases. As with any therapy, time is required for all of the safety concerns related to these potent medications to become apparent. TNF-alpha inhibitors have revolutionized the management of a number of difficult diseases, especially inflammatory arthritis, but clinicians must continue to remain aware of the potential for serious infectious complications, which now include herpes zoster."

Source: Journal of American Medical Association, 2009

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