Abstract
BACKGROUND: Sickle cell disease (SCD) is a severe genetic disorder causing anemia, pain, and organ damage, affecting millions globally. Voxelotor, approved in the United States in 2019, targeted sickle cell disease pathophysiology. Despite its therapeutic benefits, concerns remain regarding its long-term safety and potential side effects, including headaches and gastrointestinal disturbances. This study used the FDA Adverse Event Reporting System (FAERS) to assess voxelotor's safety, aiming to enhance treatment strategies and clinical decision-making in SCD management. METHODS: In this study, we utilized the FAERS to extract voxelotor-related adverse event reports from 2019 to 2024. We conducted descriptive and disproportionality analyses using four algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinkage (MGPS) to identify significant adverse event signals. The reliability of voxelotor adverse drug reactions (ADRs) was further improved by comparing with hydroxyurea ADRSs. Finally, adverse reactions were divided into acute ADRS, delayed ADRs and efficacy related reports to analyze the adverse event onset time. RESULTS: A total of 16,677,340 case reports were collected in the FAERS database, of which 20,902 reports related to voxelotor were identified. Voxelotor induced adverse events occurred in 27 system organ categories (SOC). Key system organ classes affected were the blood and gastrointestinal systems. Notably, some adverse events, such as priapism and osteonecrosis, were not listed on the drug's label. The median adverse event onset time of acute ADRs, delayed ADRs and efficacy related reports were 1, 189.5 and 271 days, respectively. CONCLUSION: This study systematically analyzed ADRs of voxelotor, highlighting the need for ongoing monitoring and further research on voxelotor's long-term safety and efficacy in treating sickle cell disease.