practicaldermatology.com
A new analysis of psoriasis patients indicates an emergence of new safety signals associated with interleukin-23 (IL-23) inhibitors and the IL-12/23 inhibitor ustekinumab.
Researchers on the study analyzed 41.4 million adverse event (AE) reports from the FDA Adverse Event Reporting System (FAERS) between 2014 and 2022, focusing on tildrakizumab, guselkumab, risankizumab, and ustekinumab. Using disproportionality analysis, researchers identified 8, 20, 107, and 115 AE signals, respectively, for these drugs. Infections and infestations emerged as the most frequently reported adverse events with all four drugs. Incidence rates observed in those taking risankizumab and ustekinumab tended to be higher.
The authors noted that risankizumab showed a notably higher incidence of AEs compared to ustekinumab, despite being a newer drug on the market and having fewer overall reports.
"Our pharmacovigilance analysis has brought to light a substantial frequency of AEs linked to IL-23 and IL-12/23 inhibitors. These findings underscore the pivotal role of IL-23 and IL-12/23 inhibitors in modulating immune function and raise concerns regarding their potential to heighten susceptibility to infections and malignancies."
The authors also noted some important limitations.
"Limitations inherent to the FAERS database, including underreporting, lack of denominator data, potential duplicate records, and inability to confirm causality, should be acknowledged of particular significance is risankizumab, which, despite having fewer reported cases and a later market introduction compared to ustekinumab, exhibited a higher incidence of AEs," they said. "These results emphasize the necessity for ongoing vigilance, further investigation, and a reevaluation of the safety profile of IL-23 and IL-12/23 inhibitors in the clinical management of psoriasis."
Source: Shi W, et al. BMC Pharmacology and Toxicology. 2025. Doi:10.1186/s40360-025-00837-y