A study has shown that people with rheumatoid arthritis who take certain drugs that block an inflammatory protein called Tumor Necrosis Factor alpha, or TNF-alpha, have an increased risk of developing the painful, blistering skin rash called shingles, which is caused by the same virus that causes chickenpox.

Though other studies have linked an increased risk of bacterial and fungal infections to the use of TNF-alpha inhibitors, the new study, by German researchers, is one the first to show that TNF-alpha blockers can increase the risk of viral infections.

The study was published in the February 18, 2009, issue of the Journal of the American Medical Association.

Anja Strangfeld, MD, of the German Rheumatism Research Center in Berlin, and her colleagues analyzed more than five years of data from registry of patients with rheumatoid arthritis. Out of 5,040 patients, the investigators identified 86 cases of shingles in 82 people. Thirty-nine of those cases started soon after treatment with an anti-TNF-alpha monoclonal antibody – either adalimumab (Humira) or infliximab (Remicade). There were 23 cases among people who had recently started therapy with etanercept (Enbrel), which is a fusion protein that inhibits TNF-alpha, and 24 cases among people taking traditional disease-modifying antirheumatic drugs, or DMARDs.

Biologic medications work by suppressing an overactive immune system. In people who have been exposed to the virus that causes chickenpox, the virus may lay dormant for years, only to flare up when the immune system drops its guard.

The results translated into an 80 percent increased risk of shingles in people taking the monoclonal antibodies, either adalimumab or infliximab, compared to people treated with traditional DMARDs. There was no increased risk noted in the etanercept users.

While an 80 percent increase in risk may sound large, Dr. Strangfeld points out that the absolute risk remains very low.

For example, in the United States, about 4 people out of 1,000 will get shingles in a year's time.

Among 1,000 people with rheumatoid arthritis treated with conventional DMARDS for one year, about six will get shingles; and among 1,000 people with RA treated for one year with adalimumab or infliximab, 11 will get shingles.

“These monoclonal antibodies have provided wonderful benefit for patients who have rheumatoid arthritis. Our patients need them,” says Richard J. Whitley, MD, a professor in the department of medicine at the University of Alabama at Birmingham, who wrote a comment on the study. “We just need to be prudent and wise in how we use them and how we look for complications.”

Both Drs. Whitley and Strangfeld recommend that patients be vaccinated against the varicella virus, the virus that causes shingles, before they start treatment on a biologic medication.

They also say patients and their doctors should be especially watchful for the early signs and symptoms of herpes zoster, the clinical name for shingles, which include fever, headache, malaise, and a feeling of burning pain, itching, or a pins-and-needles sensation.

Additionally, patients who have already had shingles are at especially high risk for a second attack if they also take a monoclonal TNF-alpha blocker and they are on high doses of glucocorticoid medications.