Real-World Safety of Symdeko: Insights from the Food and Drug Administration Adverse Event Reporting System

Su WeiLixi ZhangCuiping LiuXu Qi^*

• First Affiliated Hospital, Nanjing Medical University, Nanjing, China

Background: Symdeko, a cystic fibrosis transmembrane conductance regulator(CFTR), is widely utilized for treating cystic fibrosis (CF). Although its safety has been validated in numerous clinical trials, the real-world safety profile still needs further investagation. Methods: This study analyzed adverse event (AE) reports related to Symdeko from the FDA Adverse Event Reporting System (FAERS) spanning Q1 2018 to Q3 2024. Four disproportionality analysis methods were employed: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-Item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN). A descriptive analysis of the time to onset (TTO) of AEs was conducted, and the Weibull distribution was used to predict temporal variations in AEs. Sensitivity analysis was also implemented to refine the results. Results: This study included 5,245 AE reports. Of these, 54.9% were from females, 41.3% from males, and 62.3% from healthcare professionals. The study confirmed several known AEs, including headache, nausea, and elevated liver enzymes, and identified novel signals, such as anxiety, depression, suicidal ideation, and renal stones. In females, particular attention should be paid to dizziness, anxiety, and lower respiratory infections. In males, the occurrence of nausea and abdominal pain should be noted. For patients aged 18 and older, kidney stones should be monitored. The median time to onset (TTO) of AEs was 188 days, with 51.3% of AEs occurring after six months of treatment initiation. Sensitivity analysis further confirmed that headache, nausea, anxiety, depression, suicidal ideation, and renal stones continued to exhibit positive signals. Conclusion: The study confirmed several known AEs associated with Symdeko and identified various novel signals, providing preliminary real-world safety evidence for Symdeko. These findings underscore the importance of ongoing monitoring and management for patients treated with Symdeko. Future larger-scale prospective studies are necessary to validate these findings and enhance patient management strategies.