Use of anti-TNF therapies for inflammatory diseases does not appear to increase risk of herpes zoster

Although patients with rheumatoid arthritis (RA) have a disproportionately higher incidence of herpes zoster, an analysis that included nearly 60,000 patients with RA and other inflammatory diseases found that those who initiated anti-tumor necrosis factor (TNF) therapies were not at higher risk of herpes zoster compared with patients who initiated nonbiologic treatment regimens, according to a study appearing in the March 6 issue of JAMA.

Kevin L. Winthrop, MD, MPH, of Oregon Health and Science University, and colleagues, identified new users of anti-TNF therapy among groups of patients with RA, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis from 1998 through 2007 within a large US multi-institutional collaboration. The authors compared herpes zoster incidence between new anti-TNF users (n=33,324) and patients initiating nonbiologic disease-modifying antirheumatic drugs (DMARDs) (n=25,742) within each inflammatory disease cohort (last participant follow-up, December 31, 2007).

Across all disease indications, there were 310 herpes zoster cases among anti-TNF and 160 among nonbiologic DMARD users. For patients with RA, the researchers found that adjusted incidence rates were similar between anti-TNF and nonbiologic DMARD initiators and comparable between all three anti-TNF therapies studied. Baseline use of corticosteroids of 10 mg/d or greater among all disease indications was associated with elevated risk compared with no baseline use.

After adjustment for various factors, no significant difference in herpes zoster rates was observed within any disease indication between patients initiating anti-TNF therapy and those initiating new DMARD regimens.

Within the RA group, herpes zoster risk was associated with increasing age, female sex, overall health status, and higher-dose corticosteroid use.

“Clinicians and patients should find these results reassuring,” Dr Winthrop said. “We found that starting anti-TNF therapies such as etanercept, adalimumab, and infliximab do not increase the risk of shingles. We also found no appreciable risk difference between these individual drugs. On the contrary, we found that prednisone use does increase the risk, so that physicians and patients should try to limit long-term prednisone use and dosing if possible.”

While Dr Winthrop and colleagues found there was no increased shingles risk with anti-TNF therapies, “we verified that patients with rheumatoid arthritis particularly have high rates of disease-this has been identified in prior studies as well. Shingles is a vaccine-preventable disease.  Given patients with RA are a high-risk group, clinicians should consider vaccinating older RA patients [>50 years old] prior to beginning biologic or other immunosuppressive therapy.”

Dr Winthrop noted that the vaccine is a live virus and is currently contraindicated in those actively receiving biologic therapies such as anti-TNF therapy. Future studies are planned to see if vaccination while using anti-TNF therapy is safe and effective.

Herpes zoster is a big concern for patients at high risk, such as those with RA, according to Dr Winthrop. Approximately 1% to 2% of RA patients develop shingles each year. 

“The therapies in question suppress certain aspects of the immune system potentially important to containing the shingles virus, and prior studies had reached somewhat contradictory results with regard to whether anti-TNF therapies individually or collectively increase the risk of shingles,” he said. “This study supports the idea that this class of drugs does not increase the risk for shingles, but does highlight the dangers of prednisone use with regard to shingles.”

“The new finding that anti-TNF therapy taken by patients with rheumatoid arthritis, inflammatory bowel disease, and other autoimmune conditions may increase the incidence of herpes zoster, can be a cause for concern for many patients,” Formulary Editorial Advisor Abimbola Farinde, PharmD, MS, clinical staff pharmacist at Clear Lake Regional Medical Center, in Webster, Texas, said. “Prescribing providers should make it a point to educate patients on the fact that results have been contradicatory about the potential increased risk of shingles. It is important for providers to closely monitor patients who are on this therapy for the potential risk, immediately  address once there is a reason for concern, and consider alternative treatment options for these patients if this is required.”  ■