Post-marketing safety concerns with elagolix: a disproportionality analysis of the FDA adverse event reporting system

Objective Elagolix is approved for the treatment of moderate-to-severe pain associated with endometriosis. However, the long-term safety of elagolix in a large sample of real-world patients is unknown.

The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports were collected and analyzed from January 2019 to June 2023. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of elagolix-related adverse events (AEs).

After removing the non-drug-related AE signals, we detected several AE signals such as hot flushes, bone pain, suicidal ideation, depression, and increased liver enzymes, which were known during the clinical trial phase. In addition to this, we detected several unexpected important AEs that were not mentioned in the drug insert, including cystitis interstitial, parosmia, and epiploic appendagitis. The median onset time of elagolix-associated AEs was 28.5 days.

Our study provides a comprehensive picture of the safety of elagolix in the post-marketing setting, while also identifying potential new AE signals. These findings emphasize the importance of continued monitoring of the potential risks of elagolix. Abbreviations | AEs | = | Adverse events; | | FAERS | = | Food and Drug Administration Adverse Event Reporting System; | | ROR | = | reporting odds ratio; | | PRR | = | proportional reporting ratio; | | BCPNN | = | Bayesian confidence propagation neural network; | | MGPS | = | multi-item gamma Poisson shrinker; | | PS | = | primary suspected; | | SOCs | = | System organ classes; | | FDA | = | Food and Drug Administration; | | HMB | = | heavy menstrual bleeding; | | DRUG | = | drug file; | | DEMO | = | demographic file; | | REAC | = | reaction file; | | OUTC | = | outcome file; | | THER | = | therapy dates file; | | PRSR | = | report source file; | | INDI | = | indications for use file; | | MedDRA | = | Medical Dictionary for Regulatory Activities; | | PT | = | Preferred term; | | IC | = | information component; | | GnRH | = | gonadotrophin-releasing hormone; | | E2 | = | estradiol; | | NETA | = | norethindrone acetate; | | BMD | = | bone mineral density; | | ALT | = | alanine transaminase; | | DILI | = | drug-induced liver injury | Declaration of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties. Reviewer disclosures Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Authors’ contributions EC and YFS participated in the research design, the performance of the research, data analysis, and the writing of the paper. EC, WW performed the data analysis. WW managed and checked all the data. All authors read, checked, and approved the final manuscript. Data availability statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Supplementary material Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2024.2351451.