Low-Dose Methotrexate Exposure marginally Increases Risk of Melanoma

Methotrexate is widely used for the treatment of inflammatory disorders, including rheumatoid arthritis. Studies suggest that methotrexate may be associated with an increased risk of melanoma.

A study was conducted to determine whether methotrexate exposure is associated with an increased risk of cutaneous melanoma.

Case-control studies, cohort studies, or randomized clinical trials (RCTs) were included if they examined the odds or risk of cutaneous melanoma in individuals exposed to low-dose methotrexate in comparison with individuals unexposed. No language limitations were applied. Two independent reviewers extracted data on study characteristics and outcome data. The Meta-analysis of Observational Studies in Epidemiology guidelines were followed. To assess study quality, the Cochrane risk of bias tool was used for RCTs, and the Joanna Briggs Institute Checklist was used for cohort and case-control studies. Odds ratio from case-control studies and relative risk or hazard ratio from cohort studies or RCTs were pooled, and a random-effects model meta-analysis was conducted.

Results:

• Seventeen studies were eligible for inclusion, and of these, 12 studies with 16 642 cases of melanoma were pooled in the primary analysis.
• Indications for methotrexate included rheumatoid arthritis, psoriasis, psoriatic arthritis, and inflammatory bowel disease and were unknown in 5 studies.
• Compared with unexposed individuals, study participants with methotrexate exposure had a small increased risk of melanoma but this did not persist in a sensitivity analysis excluding the largest study
• Subgroup analyses according to comparator group or the indication for methotrexate being rheumatoid arthritis provided similar risk estimates.
• Using geographical population melanoma incidence rates, a number needed to harm of 18 630 was calculated in Australia, and 41 425 in North America.

In this systematic review and meta-analysis, low-dose methotrexate exposure was associated with an increased melanoma risk, but the absolute risk increase could be considered negligible.

Reference:

Mabel K. Yan, Charlie Wang, Rory Wolfe, Victoria J. Mar, Anita E. Wluka. Association Between Low-Dose Methotrexate Exposure and Melanoma A Systematic Review and Meta-analysis. Jama. Published online August 31, 2022.

Keywords:

Mabel K. Yan, Charlie Wang, Rory Wolfe, Victoria J. Mar, Anita E. Wluka, Association, Between, Low-Dose, Methotrexate, Exposure, Melanoma, Systematic, Review, Meta-analysis, JAMA