Rheumatoid Arthritis Drugs Raise Shingles Risk

TUESDAY Feb. 17, 2009 -- A class of medications used widely to treat rheumatoid arthritis and other autoimmune diseases might increase the risk of shingles, especially among older people and those who are also taking steroids.

But while the findings, appearing in the Feb. 18 issue of the Journal of the American Medical Association, might raise awareness of the potential complication among physicians and patients, some experts say it's unlikely to change how the drugs are used.

"We've changed people's lives with use of these anti-tumor necrosis factor drugs. People who were housebound are now leading relatively normal lives," said Dr. Guy Fiocco, an assistant professor of internal medicine at Texas A&M Health Science Center College of Medicine and director of rheumatology at Scott & White in Temple. "This modest increase in risk is not going to stop us prescribing the drug. It may make us more aware."

The increased risk did not reach clinical significance, and, Fiocco added, rheumatoid arthritis itself probably increases the risk of shingles (herpes zoster), as do steroids, which are taken by many people with the disease.

Although the link between TNF blockers and fungal and bacterial infections is fairly well-established, associations with viral infections are less clear.

There have, however, been reports of severe herpes zoster in people taking TNF blockers.

TNF blockers, which suppress the immune system, are used for a variety of autoimmune disorders, including Crohn's disease and psoriasis. In September, the U.S. Food and Drug Administration asked the manufacturers of Humira, Cimzia, Enbrel and Remicade to bolster safety warnings on the risk of developing opportunistic fungal infections. The drugs already carried black-box warnings related to different safety issues. This followed an announcement by the FDA that it would begin a safety review of the drugs, spurred by concerns that the drugs might be associated with cancer.

In the latest study, researchers from the German Rheumatism Research Centre in Berlin looked at 5,040 people taking the TNF blockers infliximab (Remicade) or adalimumab (Humira), the fusion protein etanercept (Enbrel) or the monotherapeutic drug anakinra (Kineret).

Although generally considered a TNF blocker, Enbrel was not put in that category for the study because it works with a slightly different mechanism than Remicade and Humira, explained the study's lead author, Dr. Anja Strangfeld, of the epidemiology unit at the research center in Berlin. "The target that is blocked (TNF) is the same, but it is reached with different molecular mechanisms of action," she said.

Of 86 cases of shingles that were reported in 82 participants, 39 were deemed related to treatment with one of the two TNF blockers, and 24 were attributed to treatment with conventional medications.

People taking Remicade or Humira had almost double the risk of developing shingles, the study found. According to an accompanying editorial, the risk was roughly the same as that seen in general populations over the age of 80. People in the study were, on average, in their early 50s.

Also, according to an accompanying editorial, the cases of shingles observed in the study seemed to be worse than those usually seen in the general population, with 20 percent of episodes categorized as "severe" and 13 percent requiring hospitalization.

The researchers found no statistically significant association between herpes zoster and the other drugs studied or with TNF blockers overall.

"Our recommendations [to physicians and patients] so far are limited," Strangfeld said. "As this is not enough data on the possible benefit of vaccination against shingles in older, immunosuppressed patients with a chronic disease, we are only able to advise a careful monitoring of patients under treatment with TNF blockers for early signs and symptoms of herpes zoster."

A vaccine against shingles is available and recommended for people age 60 and over, but it has not been studied in those with rheumatoid arthritis or people taking TNF blockers, the editorial indicated.

And, Fiocco pointed out, choosing a rheumatoid arthritis drug can be complicated. Given that people on Enbrel had a lower risk of developing herpes zoster than those on TNF blockers, for instance, that agent might seem to be the drug of choice for some physicians and patients.

But, he said, Medicare covers Remicade better than Enbrel and other injectable drugs.

"It's not always science that drives this," Fiocco said. "There are different finances and patient preferences. There's a lot that goes into making a decision."

More information

The National Institute of Neurological Disorders and Stroke has more on shingles.

Posted: February 2009


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