Anti-TNFs Linked to Increased Risk for Herpes Reactivation

Kate Johnson

June 13, 2012

June 13, 2012 (Berlin, Germany) — Patients with inflammatory rheumatic diseases treated with tumor necrosis factor (TNF) inhibitors have up to a 75% increased risk for herpes zoster infection, compared with those treated with traditional disease-modifying antirheumatic drugs (DMARDs), researchers reported here at the European League Against Rheumatism Congress 2012.

"This is the first meta-analysis concerning the risk of herpes virus infection in patients treated with TNF-blockers... These data raise the issue of a systematic prophylactic treatment in patients with a known history of herpetic infections, or vaccination in naïve patients," write the authors.

"What we can recommend, at this time, is to be cautious and ask patients before they start the anti-TNF drugs whether they know they are at specific risk," senior author Cédric Lukas, MD, PhD, told Medscape Medical News. "That is, even without the biologic treatment, do they already have a lot of frequent, recurrent herpetic infections? If so, then they should think about prophylaxis," said Dr. Lukas, who is a rheumatologist at Hôpital Lapeyronie in Montpellier, France.

The meta-analysis looked at 5 national registries that recorded herpes infections in patients treated with either TNF inhibitors or conventional DMARDs: the Spanish BIOBADASER; the British Society for Rheumatology Biologics Register (BSRBR); the North American CORRONA registry; a veterans registry in the United States (US veterans); and the German RABBIT registry.

The combined data provided a follow-up of 124,966 patient-years, with 74,198 patient-years in the biologic group and 50,768 patient-years in the DMARD group.

For the association between herpes zoster infections and TNF inhibitors, the investigators found a pooled odds ratio (OR) of 1.75. The registry with the strongest association was BIOBADASER (OR, 2.45), followed by CORRONA (OR, 2.34), BSRBR (OR, 1.95), RABBIT (OR, 1.82), and US veterans (OR, 1.33).

The incidence of severe herpetic infections (involving multidermatomal lesions and requiring hospitalization or intravenous treatment) was recorded by the US veterans (4.9%) and RABBIT (20.9%) registries, but was not linked to a specific treatment. The BSRBR registry recorded a higher rate of severe infections with TNF inhibitors than with synthetic DMARDs (6.00% vs 0.02%).

"Anti-TNFs, such as infliximab, adalimumab, and etanercept, have become the treatment of choice for patients with inflammatory rheumatic diseases who are uncontrolled on traditional DMARDs, but it is known that a side effect of these drugs is an increased risk of bacterial infections," said lead author Helene Che, also from Lapeyronie Hospital, in a press release. "This systematic review and meta-analysis demonstrates that careful monitoring of patients treated with anti-TNFs is required to watch for early signs and symptoms of herpes zoster, and raises the issue of when vaccination against the virus should occur."

Alberto Sulli, MD, from the University of Genova, Italy, who led a poster tour that included the this study, said that vaccination is not currently available in Europe, and that prophylaxis would be required for the duration of anti-TNF therapy. "Several drugs to treat viral infection, if used long-term, present a risk of hepatotoxicity," he told Medscape Medical News. "In Europe, we do not use prophylaxis for herpes infection when we treat patients with biologics."

"I don't think this will change the way we treat rheumatoid arthritis, but this study is important because it demonstrates that we have to look for this infection before starting treatment and during treatment."

Dr. Lukas, Ms. Che, and Dr. Sulli have disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2012: Abstract THU0368. Presented June 8, 2012.


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