Hearing Dysfunction After Treatment With Teprotumumab for Thyroid Eye Disease

Abstract

Purpose: To characterize the frequency, severity, and resolution of hearing dysfunction in patients treated with teprotumumab for thyroid eye disease (TED).

Design: Prospective observational case series.

Methods: Ophthalmic examination and adverse event assessment, including otologic symptoms, were performed at baseline, after infusions 2, 4, and 8, and at 6-month follow-up in consecutive patients who received at least 4 teprotumumab infusions. Laboratory test results were collected at baseline and during treatment. Audiometry, patulous eustachian tube (PET) testing, and otolaryngology evaluation were obtained for patients with new or worsening otologic symptoms, with a subset obtaining baseline and posttreatment testing.

Results: Twenty-seven patients were analyzed (24 females, 3 males, average 56.3 years old). Twenty-two patients (81.5%) developed new subjective otologic symptoms, after a mean of 3.8 infusions (SD 1.8). At 39.2-week average follow-up after the last infusion, most patients with tinnitus (100%), ear plugging/fullness (90.9%), and autophony (83.3%) experienced symptom resolution, whereas only 45.5% (5 of 11) of patients with subjective hearing loss/decreased word comprehension experienced resolution. Six patients underwent baseline and posttreatment audiometry, 5 of whom developed teprotumumab-related sensorineural hearing loss (SNHL) and 1 patient also developed PET. Three of the 5 patients with teprotumumab-related SNHL had persistent subjective hearing loss at last follow-up. A prior history of hearing loss was discovered as a risk factor for teprotumumab-related SNHL (P = .008).

Conclusions: Hearing loss is a concerning adverse event of teprotumumab, and its mechanism and reversibility should be further studied. Until risk factors for hearing loss are better understood, we recommend baseline audiometry with PET testing and repeat testing if new otologic symptoms develop. Screening, monitoring, and prevention guidelines are needed.

Figure 1.. Otologic Symptom Trajectory.

Circles denote timing of teprotumumab infusions. Bars represent the onset and duration of the most common otologic symptoms: Ear fullness/pressure/plugging (blue), tinnitus/popping (orange), hearing loss/word recognition/muffled hearing (yellow), and autophony (green). “x” indicates the time of last follow-up. Patients 1, 4, and 11 were lost to follow-up shortly after completing therapy. Patients 10, 13, 17, 18, 20 and 22 had pre- and post-treatment audiologic evaluation.

Figure 2.. Subjective Symptom Rate and Resolution.

Time course of otologic symptom development and resolution among 27 patients following initiation of teprotumumab. Lines illustrate the frequency and resolution of ear fullness/pressure/plugging (blue), tinnitus/popping (orange), hearing loss/word recognition/muffled hearing (yellow), and autophony (green) among the 27 patients following initiation of teprotumumab. “x” indicates the time of loss to follow-up for 3 patients.

Figure 3.

Pure Tone Audiometry (A) and Word Recognition Scores (B) for 12 ears with both pre- and post- treatment hearing testing. Overall changes were modest, with no statistically significant differences in overall world recognition or pure tone average (average at 500, 1000, 2000 and 4000 Hz). Seven of twelve ears (5 patients) demonstrated a statistically significant decline (p < 0.05) at the tested frequency (*). Four of twelve ears (2 patients) demonstrated individual word recognition score decline beyond test-retest differences (**). Bars indicate standard error.

Figure 4.. Eustachian Tube (ET) on Rigid Nasal Endoscopy of a Symptomatic Patient.

(A) Normal left ET. (B) The same patient demonstrated abnormally patent left ET after treatment with teprotumumab. Arrow denotes the reduced cartilaginous portion of the ET and star denotes the reduced fat and glandular tissue.