Rapidly progressive cognitive decline associated with teprotumumab in thyroid eye disease

Abstract

Teprotumumab (Tepezza), an insulin-like growth factor type 1 receptor antagonist, was approved for treatment of thyroid eye disease in 2020. Teprotumumab is administered intravenously every 3 weeks for a total of eight doses. Common side effects include nausea, diarrhoea, muscle spasms, hearing impairment, dysgeusia, headaches, dry skin, infusion reactions and hyperglycaemia. We report here a 76-year-old man with Graves-related thyroid eye disease who developed a rapidly progressive cognitive decline after receiving four out of eight doses of teprotumumab (cumulative dose 4620 mg). He was admitted for workup and teprotumumab infusions were discontinued. Intravenous glucocorticoids and immunoglobulin were given which showed no improvement in clinical symptoms. He subsequently underwent plasmapheresis with resolution of his symptoms, suggesting a teprotumumab-induced encephalopathy. Further studies involving larger populations and longer durations are needed.

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

“…However, relatively large doses of teprotumumab are needed to be effective (in the region of 10 g per patient per 6 month course) and commonly reported side effects include nausea, diarrhoea, muscle spasms, dry skin, infusion reactions and hypoglycaemia 26,27 . Also ototoxicity leading to permanent hearing impairment has been reported 28–30 as has rapid progressive cognitive decline (resolved following plasmapheresis) 31 …”

“… 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 …”

“…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. 2,8 Specific high affinity binding of K1-70 TM to the receptor blocks binding by patient TRAb thus preventing them from stimulating the receptor.…”

Efficacy and Safety of Teprotumumab in Thyroid Eye Disease

“…Ashraf 48 Safo 49 Kossler 52 Kossler 52 Belinsky 53 Belinsky 53 Belinsky 53 Belinsky 53 Hoang 63 Sex For personal use only.…”

Response to comment by Smith on the 2021 EUGOGO guidelines

“…reported hearing loss, cognitive decline, and amyloid encephalopathy, etc.) (8,9) are pending and warranted.…”