Methotrexate treatment and risk for cutaneous malignant melanoma: a retrospective comparative registry-based cohort study.

BACKGROUND: Methotrexate (MTX) is frequently used as an immunosuppressive drug in inflammatory diseases. It is controversial and it has not been thoroughly investigated whether MTX increases the risk of cutaneous malignant melanoma (CMM).

OBJECTIVES: The aim of the present study was to investigate whether MTX exposure increases the risk for CMM.

METHODS: A retrospective cohort study was conducted using statistics from the National Board of Health and Welfare. All patients over 18 years in the time period August 2005 to December 2014 that were dispensed MTX from Swedish pharmacies were registered (n = 101 966). For every MTX-exposed patient, five age- and sex-matched patients who had been dispensed a random drug other than MTX during the same time period were randomly selected (n = 509 279). The lists were matched with the Swedish Cancer Registry.

RESULTS: Overall, a small but statistically significant (P < 0·001) risk increase for CMM was observed in MTX-exposed patients compared with patients without MTX exposure. The Kaplan-Meier estimates for the 5-year risk of CMM was 0·48% [95% confidence interval (CI) 0·43-0·53] in the MTX-exposed group and 0·41% (95% CI 0·39-0·43) in the MTX-unexposed group. However, in a subgroup analysis, the difference between the groups was preserved only in women older than 70 years at treatment start. Moreover, there was no significant difference in incidences between the MTX-exposed and MTX-unexposed patients in the time period.

CONCLUSIONS: Our results suggest a small but significant increase in risk for CMM in patients treated with MTX. However, the risk increase observed was considerably lower than in earlier observations.