Teprotumumab-Associated Deafness: A Pharmacovigilance Analysis
Abstract
Introduction: Teprotumumab was approved in 2020 for the treatment of thyroid eye disease after the Food and Drug Administration (FDA) fast-tracked its review. Though the initial trial showed 10% hearing loss, the results of the Phase 3b/4 safety study will not be completed until 2025.
Objective/Methods: The objective of this analysis was to investigate whether a statistically significant signal exists between deafness and teprotumumab in the real-world phase four post-marketing safety data. Adverse event reports in FDA Adverse Event Reporting System (FAERS) and literature review were also analyzed to determine the severity of the hearing loss and whether the deafness is irreversible.
Results: Of the 53 adverse event reports containing teprotumumab as the medicinal product in FAERS, nine reports had an adverse event of deafness. Teprotumumab was listed as the suspect drug in all such adverse events reports. Disproportionality analysis showed a statistically significant signal between teprotumumab and deafness (PRR 95, chi-squared 744, ROR025 56 and IC025 2.9). Eight of the nine teprotumumab-associated deafness adverse event reports described the deafness as resulting in a serious or disabling condition. Literature review revealed 24 patient case reports of teprotumumab-induced hearing loss. 67% (4/6) of adverse events reports in FAERS and 57% (12/21) of patient case reports in literature for teprotumumab associated deafness specified that the deafness did not resolve after withdrawal of teprotumumab.
Conclusion: FDA should evaluate whether severe hearing loss should be listed under “warning and precautions” of teprotumumab.
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References
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