Systemic Adverse Events Associated with Teprotumumab Use: A Population-Based Pharmacovigilance Study

Background/Objectives: Teprotumumab is the first FDA-approved medication for thyroid eye disease (TED), with proven efficacy in reducing proptosis and inflammation. However, emerging reports have raised concerns about systemic adverse events (AEs). This study aimed to evaluate systemic AEs associated with teprotumumab using a population-based pharmacovigilance approach. Subjects/Methods: This population-based observational study analyzed teprotumumab-related AEs reported in the Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 2020—December 2024 using Open Vigil 2.1 software. Drug-specific AEs attributed to teprotumumab were compared to background FAERS reporting rates for other drugs. Disproportionality analyses were performed using reporting odds ratios (RORs) and Bayesian confidence propagation neural network algorithms to identify significant safety signals. Subgroup analyses by sex and age were also performed. Results A total of 3,787 AEs were attributed to teprotumumab over the study period. Teprotumumab was overreported for 28 systemic AEs (≥ 10 AEs with an ROR ≥ 10). Notably, many AEs pertained to ear and labyrinth disorders: permanent deafness (3.2%, n = 121/3,787; ROR = 9,827.3, 95%CI=[6,968.5, 13,859.1]), autophony (0.4%, n = 16/3,787; ROR = 2,366.6, 95%CI=[1,202.5, 4,657.5]), eustachian tube dysfunction (0.3%, n = 12/3,787; ROR = 147.8, 95%CI=[82.9, 263.6]), neurosensory deafness, auditory disorder, and tinnitus. Several other safety signals including but not limited to hyperglycaemia, muscle spasms, dysgeusia, menstrual disorders, onychoclasis, and gingival recession were also identified. Conclusions Heightened vigilance is needed to monitor early systemic AEs in patients administered teprotumumab. Proactive monitoring and intervention may mitigate the impact of these AEs, improving patient safety and outcomes. Future research should explore strategies to minimize or manage these AEs while preserving efficacy.