Ototoxicity and Teprotumumab

Abstract

Objectives: Teprotumumab, a novel monoclonal antibody, targets the insulin-like growth factor 1 (IGF-1) receptor. IGF-1 receptors, found in muscle and fat adjacent to the eye and implicated in Graves Ophthalmopathy, are also in the cochlea. In clinical trials, 5 participants reported self-limited audiologic symptoms but there are no objective data in the literature. The aim of this report is to describe one of the first known cases of teprotumumab-induced irreversible sensorineural hearing loss. Methods: Case report at a tertiary referral center Results: A 61 year old female with Graves ophthalmopathy presented with bilateral hearing loss, sound distortion, and tinnitus following treatment with teprotumumab. Audiogram showed mild sloping to moderately-severe sensorineural hearing loss. Repeat audiometry obtained 4 months after cessation of teprotumumab and treatment with oral corticosteroids was unchanged. Conclusions: This is one of the first descriptive cases of ototoxicity resulting in irreversible sensorineural hearing loss in the setting of treatment with teprotumumab. Periodic audiologic evaluations should be recommended to patients on teprotumumab.

Teprotumumab-associated chronic hearing loss screening and proposed treatments

“… 11 12 The magnitude of hearing loss in these cases was typically mild to moderate-severe, with no improvement on audiometry several months after discontinuation of therapy. 10 11 …”

“…The published cases of teprotumumab-associated hearing loss performed audiograms after patients reported symptoms of hearing loss. 10 11 Given that subjective hearing loss does not reliably reflect objective hearing loss, the onset of otological dysfunction in relation to drug dose and duration is unclear. 12 In addition to baseline testing, we propose regular surveillance audiometric testing ideally after every infusion throughout the therapeutic course and after drug cessation.…”

“…Oral steroids were used in one reported case of teprotumumab-associated hearing loss but were ineffective. 10 Hearing aids and cochlear implantation are options to improve functional hearing but do not address the underlying pathophysiological cause. They do not prevent or reverse otological pathology and would be needed lifelong.…”

“… 9 Multiple published cases of teprotumumab-associated hearing loss objectively demonstrated persistent and potentially permanent sensorineural hearing loss. 10–12 IGF-1 plays a significant role in the development, maintenance and protection of hearing function within the inner ear. 13 The inhibition of the IGF-1 signalling pathway by teprotumumab would explain its association with sensorineural hearing loss.…”

TSH receptor specific monoclonal autoantibody K1‐70TM targeting of the TSH receptor in subjects with Graves' disease and Graves' orbitopathy—Results from a phase I clinical trial

“…25 | 885 diarrhoea, muscle spasms, dry skin, infusion reactions and hypoglycaemia. 26,27 Also ototoxicity leading to permanent hearing impairment has been reported [28][29][30] as has rapid progressive cognitive decline (resolved following plasmapheresis). 31 In contrast to teprotumumab and other antibody drugs for GD and/or GO therapy, 3 K1-70 TM targets the TSHR directly.…”