TNF Inhibitors Do Not Increase Herpes Zoster Risk in RA

Janis C. Kelly

March 06, 2013

Herpes zoster (shingles) incidence is higher in patients with rheumatoid arthritis (RA) than in the general population but is not further elevated by TNF inhibitor treatment, Kevin L. Winthrop, MD, MPH, and colleagues report in an article published in the March issue of JAMA.

Dr. Winthrop told Medscape Medical News it would be reasonable for clinicians to conclude that (in general), TNF inhibitors can be started in patients with RA without increasing the risk for herpes zoster. Dr. Winthrop is an infectious diseases specialist at Oregon Health and Science University in Portland.

To examine the potential association between TNF inhibitors and herpes zoster, the researchers searched several databases to identify new users of anti-TNF therapy among nearly 60,000 patients with RA, inflammatory bowel disease, and psoriasis, psoriatic arthritis, or ankylosing spondylitis from 1998 through 2007. They used data from the national Medicaid and Medicare databases, Tennessee Medicaid, New Jersey's Pharmaceutical Assistance to the Aged and Disabled and Pennsylvania's Pharmaceutical Assistance Contract for the Elderly, and Kaiser Permanente Northern California. Their study was part of the Safety Assessment of Biologic Therapy initiative.

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. The researchers developed propensity scores to estimate the probability of receiving a nonbiologic DMARD. They controlled for potential confounders such as age, sex, race, urban vs rural residence, nursing home or community dwelling, comorbidities, disease severity, and herpes zoster risk factors such as history of cancer or diabetes.

Surprising Results

There were 310 herpes zoster cases among those receiving anti-TNF and 160 among nonbiologic DMARD users. For patients with RA, adjusted incidence rates were similar between anti-TNF and nonbiologic DMARD initiators (adjusted hazard ratio [aHR], 1.00; 95% confidence interval [CI], 0.77 - 1.29) and comparable between all 3 anti-TNF therapies studied (infliximab, adalimumab, and etanercept). Baseline use of corticosteroids of 10 mg/day or greater was associated with elevated risk compared with no baseline use in all disease cohorts (aHR, 2.13; 95% CI, 1.64 - 2.75).

"I was a bit surprised we found no increased risk of zoster," Dr. Winthrop said. "We controlled for changes in prednisone and methotrexate use before and after TNF start, underlying disease severity, etc, and we still managed to find no increase in zoster risk."

Coauthor Jeffrey R. Curtis, MD, MPH, told Medscape Medical News that the study data could be considered to be an argument supporting use of TNF inhibitors as a steroid-sparing approach, as long as patients are able to taper steroids if they start TNF therapy (or other biologics). Dr. Curtis is director, UAB Arthritis Clinical Intervention Program and codirector, UAB Center for Education and Research on Therapeutics at the University of Alabama, Birmingham.

Dr. Curtis added, "A key question is whether we might also be able to vaccinate patients for herpes zoster, which right now is contraindicated based on essentially no data."

James R. O'Dell, MD, Larson Professor of Internal Medicine, vice-chairman of internal medicine, and chief of the Section of Rheumatology at the University of Nebraska Medical Center in Omaha, also told Medscape Medical News that the vaccination issue is extremely important. Dr. O'Dell, who was not involved in the study, said, "The data are pretty convincing, but currently I would not give live vaccines to patients on TNF inhibitors. The most important thing to think about for clinicians still is: Use the start of a biological (especially a TNF inhibitor) as a memory tool to remind you to give all the vaccines (especially live vaccines) before starting TNF inhibitors."

Dr. Winthrop has received consulting fees from Genentech, Abbott, Pfizer, UCB Pharma, and Amgen and research grant support from Pfizer. Dr. Curtis has received consultant fees from Roche/Genentech, UCB Pharma, Centocor, Consortium of Rheumatology Researchers of North America Inc, Amgen, Pfizer, Bristol-Myers Squibb, Crescendo, and Abbott. Other authors have received consulting fees or research support from Pfizer, Merck, Amgen, Novartis, Genentech, Horizon, Apollo Health Resources Ltd, Ardea, Lilly, Regeneron, Savient, URL Pharma, Centocor, Procter and Gamble, Hoffman La Roche, Takeda, Shire, Millennium Pharmaceuticals, and Prometheus. Dr. O'Dell has disclosed no relevant financial relationships.

JAMA. 2013;309:887-895. Abstract

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