Cutaneous melanoma and JAK inhibitors: a disproportionality analysis in EudraVigilance

Pharmacovigilance aims to ensure that the risk-benefit balance remains favourable throughout the entire life-cycle of drugs. Although JAK inhibitors have been associated with the development of skin cancers, melanoma is not mentioned in their data sheets, except in the case of tofacitinib.

A case/non-case study was performed in EudraVigilance to evaluate the association between exposure to JAK inhibitors and the adverse reaction "skin melanomas(excluded ocular)" by calculating the reporting odds ratio. Additionally, univariate and multivariate analysis were performed to assess whether different variables could have an influence on melanoma development.

Until April 30, 2025, the EudraVigilance database included 158 reports with tofacitinib, 65 with ruxolitinib, 42 with upadacitinib, 21 with baricitinib, 2 with filgotinib, and 1 with abrocitinib. The reporting odds ratio analysis showed a signal between exposure to baricitinib, ruxolitinib, tofacitinib, upadacitinib, and the explored adverse reaction. Besides, when analysing the association of malignant melanoma (the most frequently coded PT in individual case reports) with different variables, a statistically significant association was observed based on the drug(p = 0.0014) and the indication(p = 0.0037).

In this EudraVigilance disproportionality analysis, signals of disproportionate reporting for cutaneous melanoma were identified for baricitinib, ruxolitinib, tofacitinib, and upadacitinib. These findings are hypothesis-generating and should not be interpreted as evidence of a causal association. Further evaluation in cohort studies, disease registries, and electronic health-record databases is required to confirm and quantify any potential association between JAK inhibitor exposure and melanoma. Given the seriousness of melanoma and the potential influence of confounding and surveillance bias, these results support maintaining clinical vigilance and appropriate dermatological monitoring in patients receiving JAK inhibitors, particularly those with additional melanoma risk factors.