Post-Marketing Safety Profile of Mirikizumab: A Multi-Database Pharmacovigilance Study Using FAERS and JADER with IL-23 Inhibitor Class Comparison.

BACKGROUND

Mirikizumab, a first-in-class interleukin-23p19 antagonist, was approved for ulcerative colitis (2023) and Crohn's disease (2025). The US Food and Drug Administration (FDA) identified a hepatotoxicity signal during pre-approval review, mandating post-marketing surveillance. No independent pharmacovigilance analysis has been published.

AIMS: To characterise the post-marketing safety profile of mirikizumab using multi-database pharmacovigilance, with a focus on hepatotoxicity and IL-23 inhibitor class comparison.

METHODS

Disproportionality analysis of the FDA Adverse Event Reporting System (FAERS; Q4 2023-Q4 2025) and Japanese Adverse Drug Event Report database (JADER) was performed using four algorithms (reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, empirical Bayesian geometric mean). Signals of disproportionate reporting were defined by concordance of all four methods. Active comparator analysis against risankizumab, guselkumab and ustekinumab, Weibull time-to-onset modelling and hepatotoxicity case characterisation were conducted. Reporting followed READUS-PV guidelines.

RESULTS

We identified 564 mirikizumab reports in FAERS and 123 in JADER. Nine signals met all four criteria in FAERS, including spontaneous abortion (Reporting odds ratio (ROR) 10.16, 95% CI 5.16-20.02), pulmonary embolism (ROR 5.56, 2.93-10.56) and injection site reactions. Hepatotoxicity showed no disproportionate reporting in either FAERS (ROR 1.19, 0.74-1.92; n = 17) or JADER (ROR 0.24, 0.05-1.19; n = 1). Comparator analysis identified cytomegalovirus infection and interstitial lung disease as mirikizumab-specific versus the IL-23 class. Weibull analysis (β = 0.65) indicated early-onset adverse event clustering.

DISCUSSION: This first multi-database pharmacovigilance study of mirikizumab did not confirm the FDA-flagged hepatotoxicity signal. Potential signals warranting further investigation include thromboembolic events and pulmonary toxicity.