Work

Potential association between IL-12/23, IL-23, and IL-17 inhibitors and skin cancer: a pharmacovigilance study based on the FAERS database

Year: 2026

Type: article

Abstract: Background Interleukin (IL)-12/23, IL-23, and IL-17 inhibitors are increasingly used for immune-mediated inflammatory diseases, yet their long-term risk of skin cancer remains unclear due to limited evidence from randomized controlled trials. Methods We conducted a disproportionality analysis using individual case safety reports from the FDA Adverse Event Reporting System (FAERS) from 2004 to 2025 Q2. Reporting odds ratios (ROR) and information components (IC) were calculated to assess the association between IL-12/23, IL-23, and IL-17 inhibitors and skin cancer. Subgroup analyses by age and sex, time-to-onset analysis, Weibull modeling, and co-medication interaction analysis were further performed. Results A total of 3,661 skin cancer reports were identified. Significant disproportionality signals were observed for most interleukin inhibitors, with the strongest associations for risankizumab (ROR 8.01, 95% CI 7.62–8.42; IC 025 , 2.88), tildrakizumab (ROR 5.81, 95% CI 4.13–8.19; IC 025 , 1.84), and ustekinumab (ROR 5.53, 95% CI 5.23–5.85, IC 025 , 2.35). IL-17 inhibitors showed weaker signals and were no longer significant in psoriasis-restricted sensitivity analyses. The association was more pronounced in elderly patients, especially for those aged >75 years. Weibull analysis indicated a wear-out failure pattern for ustekinumab and risankizumab, suggesting an increasing reporting frequency over time. Co-medication analyses did not reveal significant synergistic reporting signals. Conclusion This pharmacovigilance study identified disproportionate reporting of skin cancer in reports involving IL-12/23 and IL-23 inhibitors, particularly risankizumab and ustekinumab, with weaker signals for IL-17 inhibitors. These findings represent signal detection from a spontaneous reporting database and highlight the need for dermatological monitoring in high-risk patients, warranting further prospective investigation to clarify clinical significance.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1944368