Teprotumumab Related Hearing Loss: A Large-Scale Analysis and Review of Voluntarily Reported Patient Complaints to the Food and Drug Administration (FDA)

Purpose: Accumulating case reports and series have suggested that teprotumumab may significantly increase the risk of hearing impairment that, in some cases, does not resolve. This study investigates the association between hearing impairment and teprotumumab use. Methods: A disproportionality analysis was conducted using the United States Food and Drug Administration Adverse Event Reporting System, a publicly accessible database used for postmarketing surveillance and research. All adverse event reports containing the terms “teprotumumab” or “Tepezza” and a similar comparison group from all patients with the same indications for teprotumumab use (e.g., autoimmune thyroiditis, endocrine ophthalmopathy, and hyperthyroidism) but who had not received the drug were selected. Hearing impairment events were identified using the hearing impairment Standardized MedDRA Query. Results: A total of 940 teprotumumab-associated adverse events were identified, including 84 hearing-related adverse events, with the first reported to the Food and Drug Administration in April 2020. A comparison group of 32,794 nonteprotumumab adverse events was identified with 127 hearing-related adverse events reported. Use of teprotumumab in patients with thyroid conditions was associated with a nearly 24-fold (proportional reporting ratio [PRR] 23.6, 95% confidence interval [CI]: 18.1–30.8) increased likelihood of any hearing disorder ( p value <0.0001). The association was specifically elevated for a variety of deafness conditions (e.g., bilateral deafness [PRR: 41.9; 95% CI: 12.8–136.9]), Eustachian tube disorders (PRR: 34.9; 95% CI: 4.9–247.4), hypoacusis (PRR: 10.1; 95% CI: 7.6–13.3), and tinnitus (PRR: 8.7; 95% CI: 6.2–12.1). Conclusions: Patients treated with teprotumumab should receive warnings regarding the increased risk of hearing-related impairments and receive audiometry before, during, and after treatment.