Adverse Events Associated with IL-23 Inhibitors in the Clinical Management of Psoriasis: A Comprehensive Pharmacovigilance Analysis

Abstract Background Interleukin-23 (IL-23) inhibitors constitute a pivotal class of therapeutic agents employed in the clinical management of Psoriasis, a chronic autoimmune skin disorder. Notwithstanding their therapeutic efficacy, concerns have arisen due to the emergence of multiple adverse events (AEs) associated with their usage. This study aims to provide a comprehensive examination of the distribution and characteristics of these AEs concerning IL-23 inhibitors, with a specific focus on Guselkumab, Tildrakizumab, Risankizumab, and Ustekinumab. Methods In this research endeavor, we conducted an extensive analysis of data extracted from the FDA Adverse Event Reporting System (FAERS), spanning the timeframe from January 1, 2014, to September 30, 2022. To identify potential signals of AEs, we rigorously applied disproportionality analysis, utilizing both reporting odds ratio (ROR) and information component (IC) metrics. A signal was considered present when the lower limit of the 95% confidence interval (CI) for ROR (ROR025) exceeded one or when IC (IC025) surpassed zero, with a minimum requirement of three or more reported cases. Results Our investigation encompassed a substantial dataset, comprising a total of 41,408,408 reports detailing drug-AE associations and involving 13,271,168 individuals. Among these, 704, 13,164, 62,853, and 11,399 patients were identified as users of Tildrakizumab, Guselkumab, Ustekinumab, and Risankizumab, respectively. The analysis revealed the presence of 8, 20, 107, and 115 signals for these respective drugs. Significantly, the System Organ Class (SOC) exhibiting the highest incidence was "infections and infestations," with documented occurrences in Tildrakizumab (6/8), Guselkumab (5/20), Ustekinumab (50/107), and Risankizumab (25/115). Conclusion Our pharmacovigilance analysis has brought to light a substantial frequency of AEs linked to IL-23 inhibitors. These findings underscore the pivotal role of IL-23 inhibitors in modulating immune function and raise concerns regarding their potential to heighten susceptibility to infections and malignancies. 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. These results emphasize the necessity for ongoing vigilance, further investigation, and a reevaluation of the safety profile of IL-23 inhibitors in the clinical management of Psoriasis.