A disproportionality analysis on proprotein convertase subtilisin/kexin type 9 inhibitors and hypersensitivity and anaphylaxis

Recent case reports linked use of the lipid-lowering class of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to severe hypersensitivity reactions. Therefore, our pharmacovigilance study assessed the association between reporting of PCSK9 inhibitors and hypersensitivity or anaphylaxis. We analyzed the US Food and Drug Administration Adverse Event Reporting System (FAERS) extracting spontaneous reports from 2015 to 2023. We calculated reporting odds ratios (ROR), proportional reporting ratios, and information components (IC) as measures of disproportionate reporting of hypersensitivity or anaphylaxis with PCSK9 inhibitors overall and with specific compounds (alirocumab, evolocumab) using the entire FAERS as comparator. In sensitivity analyses, we adjusted for demographic characteristics, used statins as active comparator, and applied alternate outcome definitions. Among all reports in FAERS during the study period involving PCSK9 inhibitors, we identified 12,591 cases of hypersensitivity and 17,214 cases of anaphylaxis. Across disproportionality analysis methods, we did not observe an association between the reporting of PCSK9 inhibitors or evolocumab specifically and the outcomes. However, there were associations with alirocumab and hypersensitivity (ROR, 1.14; 95% confidence interval [CI], 1.11-1.18 / IC, 0.19; 95% credible interval [CrI], 0.14-0.24) and with alirocumab and anaphylaxis (ROR, 1.30; 95% CI, 1.26-1.33; IC, 0.37; 95% CrI, 0.33-0.42). Sensitivity analyses corroborated the lack of an association with PCSK9 inhibitors or with evolocumab and were inconsistent regarding alirocumab. Our large pharmacovigilance study showed no signal of disproportionate reporting for hypersensitivity or anaphylaxis with PCSK9 inhibitors overall. The inconsistencies in alirocumab related findings argue against a compound specific signal.