FAERS study finds skin-cancer reporting signals for select interleukin inhibitors

Skin cancer was disproportionately reported in adverse-event records involving several IL-12/23, IL-23 and IL-17 inhibitors in a pharmacovigilance study of the US FDA Adverse Event Reporting System (FAERS). Researchers analysed individual case safety reports submitted from 2004 through the second quarter of 2025 and identified 3,661 reports mentioning skin cancer. The strongest statistical signals occurred for risankizumab, tildrakizumab and ustekinumab, while signals for IL-17 inhibitors were weaker and were no longer significant when the analysis was restricted to reports involving psoriasis.

The investigators used disproportionality analysis to assess whether skin cancer appeared more often than expected among reports involving particular medicines. This approach generated reporting odds ratios (RORs) and information components (ICs) from the spontaneous-reporting data. Risankizumab had the strongest measured signal, with an ROR of 8.01, a 95% confidence interval of 7.62–8.42 and an IC025 of 2.88. Tildrakizumab had an ROR of 5.81, with a 95% confidence interval of 4.13–8.19 and an IC025 of 1.84. Ustekinumab had an ROR of 5.53, with a 95% confidence interval of 5.23–5.85 and an IC025 of 2.35. These measures quantify disproportionate reporting within FAERS; they do not establish that the medicines caused skin cancer or show the magnitude of any absolute increase in incidence.

Subgroup analyses indicated that the reporting association was more pronounced among older patients, particularly those older than 75 years. The researchers also performed time-to-onset analysis and Weibull modelling to examine reporting patterns after treatment initiation. The modelling identified a “wear-out” failure pattern for ustekinumab and risankizumab, indicating that the frequency of reports increased over time in the dataset. This pattern describes when reports accumulated; it does not demonstrate that cancer risk itself rises with longer treatment. Additional analyses of interactions with co-medications did not identify significant synergistic reporting signals for skin cancer.

The findings are best understood as signal detection from a spontaneous-reporting database rather than a comparison of cancer incidence among treated and untreated groups. The study’s population comprised individual safety reports entered into FAERS, and its results concern reporting associations for IL-12/23, IL-23 and IL-17 inhibitors during the specified period. The authors concluded that disproportionate skin-cancer reporting warrants further prospective investigation to establish its clinical significance, particularly for risankizumab and ustekinumab. Their results do not demonstrate that the medicines cause skin cancer, quantify absolute risk or establish that the observed reporting pattern reflects a change in the incidence of skin cancer. The findings also do not support treating the weaker IL-17 inhibitor signals as causally established, especially after they disappeared in the psoriasis-restricted sensitivity analysis.

Subject of Research: FAERS disproportionality analysis of skin-cancer reporting involving IL-12/23, IL-23 and IL-17 inhibitors.

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

Article References: Jiang, X., Huang, Y., Xie, M., Peng, L., Xu, M., Qi, Z., Wang, G., & Pu, X. (2026). Potential association between IL-12/23, IL-23, and IL-17 inhibitors and skin cancer: a pharmacovigilance study based on the FAERS database. Frontiers in Pharmacology, 17, Article 1944368. https://doi.org/10.3389/fphar.2026.1944368

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1944368

Keywords: FAERS, pharmacovigilance, skin cancer, disproportionality analysis, IL-23 inhibitors, IL-17 inhibitors, risankizumab, ustekinumab, tildrakizumab, adverse-event reporting, Potential, association