TNF agents for rheumatic diseases associated with increased skin cancer risk

Tumor necrosis factor inhibitors (TNFi) used to treat rheumatoid arthritis are associated with an increased risk of skin cancer but not lymphoma, according to a meta-analysis.

To assess the risk of malignancy in patients with rheumatoid arthritis treated with TNFi, researchers did a meta-analysis of published literature and, to reduce publication bias, included conference abstracts published by three rheumatology medical societies.

Twenty-one full texts and eight abstracts met the inclusion criteria of prospective, observational studies of more than 100 patients receiving TNFi for rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. No retrospective studies were included. The studies included 40,000 patients and almost 150,000 cumulative years of exposure. Results appeared in the September Annals of the Rheumatic Diseases.

The pooled estimate among seven studies that included relative risk for all-site malignancy was 0.95 (95% CI, 0.85 to 1.05) for patients treated with TNFi compared to non-exposed patients. Two studies reported there was no evidence that longer exposure to TNFi agents increased the risk of malignancy.

In patients with previous malignancies, there was a higher risk of a new/recurring malignancy, the researchers noted. The overall incidence of malignancy in patients with rheumatoid arthritis ranged from 3.88 (95% CI not reported) per 1,000 patient-years to 9.34 (95% CI, 8.19 to 10.60) per 1,000 patient-years in the included studies. But in two studies among patients with previous malignancy, rates were much higher: 25.3 (95% CI 13.4 to 43.2) per 1,000 patient-years and 45.5 (95% CI 20.8 to 86.3) per 1,000 patient-years. This risk was not higher in patients who had been exposed to TNFi compared to those who hadn't, although researchers noted the confidence intervals were wide.

Results from four studies showed that patients treated with TNFi have a significantly increased risk of developing a non-melanoma skin cancer (1.45, 95% CI, 1.15 to 1.76). In addition, patients are at an increased risk of developing melanoma, as the pooled estimate from two studies was 1.79 (95% CI, 0.92 to 2.67). The pooled estimate for the risk of lymphoma was 1.11 (95% CI, 0.70 to 1.51).

“This systematic review and meta-analysis provides reassurance to physicians and patients that the treatment of RA patients with TNFi does not increase the risk of malignancy, particularly lymphoma,” the authors wrote. “However, it does appear to increase the risk of skin cancer, including melanoma. The [confidence intervals], however, do not preclude an effect of treatment on the risk for specific malignancies, and researchers should be encouraged to publish additional analyses to add to the evidence base.”