Teprotumumab and sensorineural hearing loss: a propensity score-matched retrospective cohort study.

Teprotumumab, a monoclonal antibody that antagonizes the insulin-like growth factor 1 receptor, is the first medication within the United States to receive Food and Drug Administration (FDA) approval for thyroid eye disease (TED). The FDA recently issued a warning regarding otologic complications, such as hearing loss. We aimed to study the association between teprotumumab and sensorineural hearing loss in thyrotoxic patients with TED. A real-world retrospective cohort study was performed through the TriNetX Collaborative Network (globally de-identified database) over a 5-year period. Inclusion criteria were patients at least 18 years of age with a diagnosis of Graves' disease and TED, and were stratified into two cohorts: those treated with teprotumumab and those who were not. Propensity score-matching was performed for an even balance among cohorts (adjusting for age, sex, race, ethnicity, comorbidities, medications, smoking, and laboratory values), providing 532 patients per cohort. We identified a significantly higher risk difference of sensorineural hearing loss in patients treated with teprotumumab compared to those without exposure (risk difference 8.415%, 95% CI 4.954-11.876; 12.222 versus 3.808%), with a near three-fold increased relative risk for acquiring sensorineural hearing loss (risk ratio 3.21, 95% CI 1.936-5.323, P < 0.0001) over a 5-year period. Although the mechanism of teprotumumab-induced hearing loss remains unknown, and there is a lack of data to identify patients at risk (or those more likely to recover), our study confirms a higher risk for sensorineural hearing loss, which patients and providers alike must be aware of. Further studies providing prospective data are required to confirm such findings.