Potential cerebrovascular accident signal for risankizumab: A disproportionality analysis of the FDA Adverse Event Reporting System (FAERS)

The interleukin-23 (IL-23) inhibitor risankizumab was recently approved for the treatment of moderate-to-severe plaque psoriasis in the United States. Low rates of cerebrovascular accident (CVA) were observed in risankizumab-treated patients during clinical trials. The aim of this study was to determine whether risankizumab may be associated with CVA in a real-world setting.A retrospective disproportionality analysis was conducted utilizing postmarketing adverse event reports submitted to the US Food and Drug Administration Adverse Event Reporting System (FAERS) through the fourth quarter of 2021. A custom query consisting of 22 CVA-related Medical Dictionary for Regulatory Activities (MedDRA) preferred terms previously reported in clinical trials of plaque psoriasis medications was used to identify cases. Disproportionality was measured by calculating reporting odds ratios (ROR) and 95% confidence intervals (CI), whereby the lower limit of a 95% CI >1.0 and ≥ three cases was considered a signal.Risankizumab was associated with significantly disproportionate CVA reporting compared to all other drugs in FAERS (ROR 2.48; 95% CI 2.14-2.88) as well as 11 alternative plaque psoriasis therapeutics across five pharmacologic classes. The largest disproportionality signals for risankizumab were identified relative to apremilast (ROR 9.07; 95% CI 7.56-10.89), ixekizumab (ROR 6.75; 95% CI 5.14-8.86), guselkumab (ROR 6.74; 95% CI 4.68-9.71), certolizumab (ROR 5.70; 95% CI 4.74-6.85) and etanercept (ROR 4.91; 95% CI 4.21-5.73).This study detected a previously unreported signal of disproportionate CVA reporting with the real-world use of risankizumab. Further long-term observational data will be necessary to better characterize this unconfirmed potential safety signal.