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Methotrexate use associated with increased risk of some skin cancers

New findings from the University of Gothenburg in Sweden show that methotrexate (MTX) use is associated with a higher risk of skin cancer at a group level.

Published in the British Journal of Cancer, the findings come from an analysis of medical records from Danish healthcare registries. Investigators identified patients born in any of the Nordic countries who, between 2004 and 2018, were diagnosed with one of three types of skin cancer: basal cell carcinoma (BCC, 131,447 patients), squamous cell carcinoma (SCC, 18,661 patients), and cutaneous malignant melanoma (CMM, 26,068 patients). Every patient with skin cancer was compared with 10 age and sex-matched controls.

The results showed that, at a group level, it was more common for patients who developed any of the three types of skin cancer to have been treated with MTX previously. This rise in risk is presented in the study as a range of 20–38% for BCC, 37–89% for SCC, and 13-61% for CMM. Patients who had been prescribed higher doses of MTX were at higher risk for SCC and BCC. In contrast, no distinct dose–response relationship was observed for CMM.

The study’s first author, Sam Polesie, MD, PhD, is an associate professor (docent) of dermatology and venereology at Sahlgrenska Academy, University of Gothenburg, and a dermatologist at Sahlgrenska University Hospital. He points out in a press release that the study’s findings should not be used at an individual level.

“MTX is an effective and important medicine that helps lots of patients. The absolute risk for an individual patient of developing any of these skin cancer types remains small even if they use the drug. However, since MTX is a quite frequently used drug, our results may imply a rise in the number of skin cancer cases at the population level,” Dr. Polesie said.

When the researchers looked specifically at data on patients with psoriasis, they found no statistical correlation linking MTX to a heightened SCC or CMM risk. However, a rise in BCC risk remained.

“You could interpret this as a weakness in the study. It’s possible that the statistical analyses conceal some type of bias that was evident among patients with psoriasis, but we can only speculate about that. These results might also be interpreted as reassuring to dermatologists who mainly use MTX as the first line therapy of systemic drugs to treat patients with moderate to severe psoriasis,” said Dr. Polesie.

“Patients with psoriasis probably have divergent sun exposure habits. Moreover, historically light therapy used to be a common treatment to treat psoriasis. Sun exposure habits and use of light therapies were examples of important factors we weren’t able to include in the study.”


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