Study Finds Use of Methotrexate Can Increase Risk of Skin Cancer – Latest Scientific and Practical Based Pharmacy Info

Pharmaceutical Magazine – Methotrexate (MTX) can increase a person’s risk of basal cell carcinoma (BCC), squamous cell carcinoma of the skin (cSCC), or malignant melanoma of the skin (CMM), according to a study published in the journal Nature. The current findings do not suggest that there is a dose-dependent increase in CMM risk with MTX. Conversely, when the cumulative dose is increased, MTX appears to exacerbate the risk of developing BCC and cSCC, according to the researchers.

“Use of cumulative MTX doses ≥2.5 g was associated with an increased risk of BCC, cSCC and CMM compared with no use of MTX… The specific indications for MTX treatment deserve discussion because the indications themselves may be associated with an increased risk of skin cancer,” wrote the study authors.

MTX is an essential drug, as defined by the World Health Organization (WHO). Immunosuppressive drugs are used for dermatological and rheumatological conditions, but these treatments are associated with photosensitizing properties. Both immunosuppression and photosensitization are associated with an increased risk of skin cancer.

The Cardiovascular Inflammation Reduction Trial (CIRT) reported that MTX doubled the risk of skin cancer compared with placebo, but this study had a short follow-up and no qualified clinical prescribing practice. The current study was conducted to determine the risk of developing BCC, cSCC, and CMM from MTX, evaluating the national health registry and demographics of patients from Denmark who developed any of the 3 cancers between 2004 and 2018.

The data showed that 233 (1.2%) patients with cSCC cases were exposed to MTX with a cumulative dose of 2.5 g or more—patients numbered 1214 (0.9%) for BCC, and 183 (.07%) for CMM. MTX is often used to treat patients with severe psoriasis, but the current study found no association between CMM and cSCC risk among patients with psoriasis, despite the results of previous studies.

One such study came out of Sweden, which showed that MTX use was invariably associated with cSCC in psoriasis patients. A different meta-analysis of 16,642 melanoma cases associated MTX with a small increased risk overall and the CIRT study observed that MTX had the highest hazard ratio (HR) for cSCC. Although several studies have evaluated MTX with skin cancer risk, there is no unanimous conclusion, according to the authors of the current study.

This study is limited in that no data is available on sun exposure, so the authors cannot exclude UV exposure as a confounding variable. In addition, this study was conducted in people born in the Nordic countries, which was mainly limited to skin types 1 and 3. Furthermore, people using MTX were more likely to have skin checks, which could lead to surveillance bias.

“Our findings… cannot support that skin cancer risk should be an important consideration when prescribing MTX,” the study authors wrote in the article. “However, our findings do deserve further attention for future investigations which ideally include data on UV exposure.”

Reference

Polesie S, Gillstedt M, Schmidt S, Egeberg A, Pottegård A, Kristensen K. Use of methotrexate and risk of skin cancer: a nationwide case–control study. Br J Cancer (2023). doi.org/10.1038/s41416-023-02172-7