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Anti-TNF antibody treatment may raise risk of shingles

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – In patients with rheumatoid arthritis, anti-tumor necrosis factor (TNF) treatment with adalimumab and infliximab is associated with a small increased risk of herpes zoster, researchers report in the Journal of the American Medical Association for February 18.

The anti-TNF receptor fusion protein etanercept, on the other hand, appears to have a neutral effect on shingles incidence.

Although increased risk of bacterial infection is a well known consequence of treatments targeting TNF, little is known about the associated risk of viral infection, Dr. Anja Strangfeld, at the German Rheumatism Research Center in Berlin, and co-authors note. However, herpes zoster is one of the most common adverse events reported in clinical trials of TNF blockers.

Their prospective cohort study involved patients enrolled in the German biologics register RABBIT between May 2001 and December 2006, upon initiation of treatment with infliximab (591), etanercept (1252), or adalimumab (1423). A control group comprised 1774 patients who were switching therapy after failing primary therapy with their first disease-modifying antirheumatic drug (DMARD).

There were 86 cases of herpes zoster among 82 patients, the report indicates. Eighteen cases were serious, including 12 that required hospitalization. The three documented complications were postherpetic neuralgia in two patients, and multidermatomal zoster with esophagitis and pulmonary involvement in one patient.

The authors attribute 39 cases to treatment with anti-TNF antibodies, 23 to etanercept, and 24 to conventional DMARDS, which translated to crude incidence rates per 1000 patient-years of 11.1, 8.9 and 5.6, respectively.

After adjusting for age, disease severity, and steroid use, monoclonal antibody treatment was associated with significantly increased risk of herpes zoster (hazard ratio 1.82), “although this risk was lower than the threshold for clinical significance,” the team notes.

The risk was not significantly increased among etanercept users.

Serious complications were far less common than in previous clinical trials, which the investigators attribute to “efficient antiviral treatments” now available.

They conclude by recommending “careful monitoring of patients treated with monoclonal anti-TNF-alpha antibodies for early signs and symptoms of herpes zoster.”

This advice is endorsed by editorialists Dr. Richard J. Whitley and Dr. John W. Gnann, Jr. at the University of Alabama at Birmingham, who write, “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.”

JAMA 2009;301:737-744,774-775.