TNF Inhibitors May Increase Nonmelanoma Skin Cancer Risk

August 15, 2011 — Data from over 20,000 US military veterans show that nonmelanoma skin cancer (NMSC) risk is about one third higher for patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors than for similar patients treated with nonbiologic disease-modifying antirheumatic drugs (DMARDs). The study, led by Wassila Amari, MD, appears in the August issue of Rheumatology.

Senior author Prabha Ranganathan, MD, from the Department of Medicine at Washington University School of Medicine, St. Louis, told Medscape Medical News that for patients with RA treated with TNF inhibitors, "a complete skin exam by a dermatologist [should be done] once a year."

However, Dr. Ranganathan also warned against overinterpretation of the data. "It is intriguing that NMSC risk is increased in patients on anti-TNFs, while most studies to date show that overall cancer risk is not increased in these patients. But this is an observational study, so association does not equal causality," Dr. Ranganathan said.

The researchers examined skin cancer risk in a cohort of 20,648 patients with RA using data from US Department of Veterans Affairs databases. They defined skin cancer as first occurrence of International Classification of Diseases, 9th revision, Clinical Modification, diagnosis code for NMSC after initiation of a biologic or nonbiologic DMARD.

Incidence of NMSC was 18.9/100 patient-years in patients receiving TNF inhibitors and 12.7/100 patient-years in patients receiving nonbiologic DMARDs. The hazard ratio for NMSC was 1.42 for TNF inhibitors vs nonbiologic DMARDs. Risk was greater in patients who were older, were male, had used nonsteroidal anti-inflammatory drugs or glucocorticoids, or had prior malignancies.

"TNF-alpha antagonist therapy in veterans with RA may be associated with an increased risk of NMSC," the authors conclude. "This result should prompt rheumatologists to carefully and systematically screen all patients on TNF-alpha antagonists periodically for skin cancer and pre-cancerous lesions."

Kaleb Michaud, PhD, assistant professor of medicine at the University of Nebraska Medical Center, Omaha, and co-director of the National Data Bank for Rheumatic Diseases, reviewed the study for Medscape Medical News.

Dr. Michaud said, "All observational studies have details that can be critiqued, and I do feel they should have conducted some sensitivity analysis with their treatment group by allowing patients to switch back and forth between exposure groups and by looking at other comorbidities that would lead to being switched from a treatment group."

"Overall their study is well done and is an important contribution to the scarce literature on this subject. While our studies show an association between anti-TNF usage and skin cancer, it's still unclear if this is a causal relationship and whether or not aggressive screening beforehand or during treatment would be beneficial," Dr. Michaud said.

Dr. Ranganathan and Dr. Michaud have disclosed no relevant financial relationships.

Rheumatology. 2011;50:1431-1439. Abstract

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