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Safety Profile of PCSK9 Inhibitors (Master thesis)

Δερμίκη - Γκάνα, Φωτεινή/ Dermiki - Gana, Fotini

Spontaneous adverse event reporting systems such as the FDA Adverse Event Reporting System (FAERS) are integral in the monitoring of the safety profile of drugs. FAERS contributes to the exploration of unknown drug-adverse event associations based on real-world data. Objective To detect potential safety signals related to hypersensitivity/anaphylaxis associated with PCSK9 inhibitors (alirocumab, evolocumab). Methodology A retrospective pharmacovigilance study was conducted, querying FAERS in the year 2018 for reports including PCSK9 inhibitors. We estimated several measures of disproportionate reporting of hypersensitivity and anaphylaxis associated with use of PCSK9 inhibitors: reporting odds ratio (ROR) with 95% confidence interval (CI), proportional reporting ratio (PRR) with 95% CI, and the Bayesian Confidence Propagation Neural Network with the information component and 95% credible intervals, using the full FAERS dataset as the reference set. In sensitivity analyses, we used a stricter outcome definition and statins as an active comparator. Results The number of cases linking PCSK9 inhibitors to hypersensitivity is 900, of which 79.67% were associated with evolocumab, while the incidents of anaphylaxis for these specific drugs were calculated at 493. The average age of patients with a direct correlation to a PCSK9 inhibitor was 66.8 years. Physicians and nurses submitted the majority of the reports to FAERS. No significant potential association was found between PCKS9 inhibitors and hypersensitivity/anaphylaxis incidents based on the investigation of ROR and PRR values that ranged below 1. Conclusions This pharmacovigilance study, based on data from 2018, represents a snapshot of a real-world investigation. Apart from demographic information, it provides indications for the need for further pharmacoepidemiological research on the safety of PCSK9 inhibitors.