Tumor necrosis factor (TNF) inhibitors—biologic agents used in the treatment of rheumatoid arthritis—appear to increase the risk of skin cancer, including melanoma, based on the results of a systematic review and meta-analysis. These agents include the monoclonal antibodies infliximab and adalimumab, and the protein etanercept.

Persons with inflammatory arthritis in general and particularly rheumatoid arthritis have an increased risk of malignancy, especially lymphoma and lung cancer. However, they have a reduced risk of developing colorectal and breast cancers. The effect of treatments acting on the immune system may influence these risks, but limited patient numbers and relatively short duration of exposure to treatment make this difficult to study.

Professor Xavier Mariette of the rheumatology service at Bicêtre Hospital in suburban Paris, France, and colleagues searched for prospective, observational studies to help them assess the risk of malignancy in persons with rheumatoid arthritis who were treated with TNF inhibitors. The search yielded 21 full texts and eight conference abstracts that met the inclusion criteria, involving more than 40,000 patients and nearly 150,000 cumulative years of exposure to TNF inhibitors.

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The pooled estimate for the risk of all-site malignancy from seven of the studies was 0.95, indicating negligible or no increased risk of malignancy overall for users of TNF inhibitors. Two studies further indicated that there was no evidence that long-term use of these agents increased cancer risk. And although persons with a history of cancer were more likely to be diagnosed with the disease again, this risk was not affected by exposure to TNF inhibitors.

However, compared with persons not taking TNF inhibitors, four studies showed that patients undergoing such treatment were 45% more likely to develop a nonmelanoma skin cancer, and two studies indicated a 79% increased risk for melanoma.

“This systematic review and meta-analysis provides reassurance to physicians and patients that the treatment of [rheumatoid arthritis] with TNF inhibitors does not increase the risk of malignancy, particularly lymphoma,” concluded Mariette’s team in Annals of the Rheumatic Diseases. “However, it does appear to increase the risk of skin cancer, including melanoma.”

The investigators added that the confidence intervals of the studies do not preclude an effect of treatment on the risk for specific malignancies, and that more analyses should be done.