Risk of audiologic side effects with teprotumumab treatment for thyroid eye disease: propensity matched analysis

Jonathan C Markle¹, Anil Johanis², Jacqueline K Shaia^{1

3}, Daniel Benito⁴, Katherine E Talcott^{1

5}, Rishi P Singh^{6

7

8}

Affiliations

¹ Center for Ophthalmic Bioinformatics, Cleveland Clinic, Cole Eye Institute, Cleveland, OH, USA.
² Case Western Reserve School of Medicine, Cleveland, OH, USA.
³ Department of Population and Health Quantitative Health Sciences, Case Western Reserve School of Medicine, Cleveland, OH, USA.
⁴ Cleveland Clinic Martin Hospitals, Cleveland Clinic Florida, Stuart, USA.
⁵ Retina Service, Cleveland Clinic Cole Eye Institute, Cleveland, OH, USA.
⁶ Center for Ophthalmic Bioinformatics, Cleveland Clinic, Cole Eye Institute, Cleveland, OH, USA. SINGHR@ccf.org.
⁷ Cleveland Clinic Martin Hospitals, Cleveland Clinic Florida, Stuart, USA. SINGHR@ccf.org.
⁸ Retina Service, Cleveland Clinic Cole Eye Institute, Cleveland, OH, USA. SINGHR@ccf.org.

PMID: 39668181
PMCID: PMC11978748 (available on 2026-04-01)
DOI: 10.1038/s41433-024-03531-1

Risk of audiologic side effects with teprotumumab treatment for thyroid eye disease: propensity matched analysis

Jonathan C Markle et al. Eye (Lond). 2025 Apr.

. 2025 Apr;39(6):1107-1114.

doi: 10.1038/s41433-024-03531-1. Epub 2024 Dec 12.

Authors

Jonathan C Markle¹, Anil Johanis², Jacqueline K Shaia^{1

3}, Daniel Benito⁴, Katherine E Talcott^{1

5}, Rishi P Singh^{6

7

8}

Affiliations

¹ Center for Ophthalmic Bioinformatics, Cleveland Clinic, Cole Eye Institute, Cleveland, OH, USA.
² Case Western Reserve School of Medicine, Cleveland, OH, USA.
³ Department of Population and Health Quantitative Health Sciences, Case Western Reserve School of Medicine, Cleveland, OH, USA.
⁴ Cleveland Clinic Martin Hospitals, Cleveland Clinic Florida, Stuart, USA.
⁵ Retina Service, Cleveland Clinic Cole Eye Institute, Cleveland, OH, USA.
⁶ Center for Ophthalmic Bioinformatics, Cleveland Clinic, Cole Eye Institute, Cleveland, OH, USA. SINGHR@ccf.org.
⁷ Cleveland Clinic Martin Hospitals, Cleveland Clinic Florida, Stuart, USA. SINGHR@ccf.org.
⁸ Retina Service, Cleveland Clinic Cole Eye Institute, Cleveland, OH, USA. SINGHR@ccf.org.

PMID: 39668181
PMCID: PMC11978748 (available on 2026-04-01)
DOI: 10.1038/s41433-024-03531-1

Abstract

Background/objectives: Patients with thyroid eye disease (TED) taking teprotumumab have reported audiologic symptoms as a side effect; however, limited real world data and large sample sizes have been utilized to evaluate this relationship.

Methods: A retrospective cohort study was created in TriNetX to identify patients with TED utilizing ICD-10, CPT, and Healthcare Common Procedure coding systems. TED patients with and without teprotumumab treatment were analysed with greedy one-to-one propensity matching. Appearance of one or more new ICD-10 codes corresponding to audiologic outcomes of interest (tinnitus, sensorineural hearing loss, hypoacusis, hyperacusis, autophony, Eustachian tube dysfunction) served as the outcome of interest. Patients with a history of hearing impairment were also evaluated for worsening hearing loss after initiation of teprotumumab.

Results: Within the entire TriNetX cohort, 88 out of 441 patients with a diagnosis code for TED treated with teprotumumab had new appearance of an audiologic outcome within TriNetX. After matching, the relative risk for TED patients who were exposed to teprotumumab for new audiologic symptoms was increased with a risk ratio (RR) of 2.85 [95% CI 1.94, 4.20] compared to TED patients not exposed to teprotumumab. Of 51 patients with a history of hearing impairment and TED, 14 had record of new audiologic testing after teprotumumab administration (RR = 1.90 [0.96, 3.78]) compared to unexposed patients.

Conclusions: This study affirms previous research stating that TED patients receiving teprotumumab are at an increased risk of new audiologic side effects when compared to TED patients not using teprotumumab.

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Conflict of interest statement

Competing interests: KET reports personal fees from Genentech/Roche, Apellis, Alimera, Iveric Bio, Bausch and Lomb, and EyePoint; research fees from Zeiss and Regenxbio. RPS reports personal fees from Genentech/Roche, Alcon, Novartis, Regeneron, Asclepix, Gyroscope, Bausch and Lomb, and Apellis. All other authors report no disclosures.

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Risk of audiologic side effects with teprotumumab treatment for thyroid eye disease: propensity matched analysis

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Risk of audiologic side effects with teprotumumab treatment for thyroid eye disease: propensity matched analysis

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