Analysis of the association between Janus kinase inhibitors and malignant skin tumors using the Food and Drug Administration Adverse Event Reporting System

Abstract Background Malignant skin tumor (MST) is one of the most concerning possible adverse events of Janus kinase (JAK) inhibitors, while the risk of drug-related MST events remains unproven. Aim This study aimed to evaluate the association between JAK inhibitors and adverse events of MST and to characterize the main features of drug-related MSTs. Method Data (2012 to 2021) were collected using the US Food and Drug Administration Adverse Event Reporting System (FAERS). Adverse event cases of JAK inhibitors as the primary suspected (PS) drug were extracted explicitly for further analysis. Disproportionality analysis evaluated the association between JAK inhibitors and MST events by estimating the reporting odds ratio (ROR) and the information component (IC) with a 95% confidence interval (95% CI). Results A total of 142,673 cases with JAK inhibitors as a PS drug were collected from FAERS, including 1,400 cases of MST events. Ruxolitinib, upadacitinib, tofacitinib, and baricitinib were included in the disproportionality analysis. Three JAK inhibitors were associated with MST events, including ruxolitinib (ROR 5.40, 95%CI 5.03–5.81; IC 2.39, 95%CI 2.14–2.62), upadacitinib (ROR 4.79, 95%CI 4.03–5.71; IC 2.24, 95%CI 1.62–2.77), and tofacitinib (ROR 1.67, 95%CI 1.53–1.83; IC 0.73, 95%CI 0.43–1.02). The median time to onset of MST events was 378.5 days. Conclusion The data mining of FAERS suggested an association between MSTs and ruxolitinib, upadacitinib, and tofacitinib. More attention should be paid to MST events when prescribing JAK inhibitors in clinical practice.