Potential association between IL-12/23, IL-23, and IL-17 inhibitors and skin cancer: a pharmacovigilance study based on the FAERS database
- 1Department of Pharmacy, People’s Hospital of Mianzhu
- 2Department of Pharmacy, The Affiliated Hospital, Southwest Medical University
- 3School of Pharmacy, Southwest Medical University
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.
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BibTeX
@article{jiang2026potential,
title = {{Potential association between IL-12/23, IL-23, and IL-17 inhibitors and skin cancer: a pharmacovigilance study based on the FAERS database}},
author = {Xing Jiang and Yunbei Huang and Min Xie and Li Peng and Mengyao Xu and Zhongyu Qi and Guojun Wang and Xiaofeng Pu},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1944368},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1944368/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Potential association between IL-12/23, IL-23, and IL-17 inhibitors and skin cancer: a pharmacovigilance study based on the FAERS database
AU - Xing Jiang
AU - Yunbei Huang
AU - Min Xie
AU - Li Peng
AU - Mengyao Xu
AU - Zhongyu Qi
AU - Guojun Wang
AU - Xiaofeng Pu
PY - 2026
DA - 2026/10/22
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1944368
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1944368/full
AB - 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.
SN - 1663-9812
ER -