Teprotumumab: A Review in Thyroid Eye Disease

Teprotumumab (TEPEZZA®), a monoclonal antibody that inhibits the insulin-like growth factor 1 receptor (IGF-1R), is the first disease-modifying therapy approved for the treatment of thyroid eye disease (TED) in the USA. In phase II and III clinical trials in adults with active, moderate-to-severe TED, intravenous teprotumumab significantly improved proptosis response rate and a range of other TED outcomes, including overall response rate, Clinical Activity Score, diplopia and disease-specific quality of life. The clinical benefit of teprotumumab was maintained for up to 51 weeks post-treatment in the majority of patients. Teprotumumab was generally well tolerated; adverse events with the greatest risk difference compared with placebo were muscle spasms, hearing loss and hyperglycaemia. Early real-world experience suggests teprotumumab may also be beneficial in a more diverse TED population. Teprotumumab is the first approved treatment for TED and is effective at reducing symptoms which are often unamenable to historical pharmacological interventions. While further data are required, current evidence suggests teprotumumab represents an important advance in the treatment of TED.Thyroid eye disease (TED) is an inflammatory disease that involves expansion of the soft tissue surrounding and behind the eye. It can lead to bulging of the eye(s), double vision, optic nerve compression and vision loss. Traditional treatments are often unsatisfactory. Insulin-like growth factor 1 receptor (IGF-1R) signalling is implicated in the progression of TED, leading to the development of teprotumumab (TEPEZZA®). Teprotumumab, administered intravenously, is a first-in-class monoclonal antibody that inhibits IGF-1R. In clinical trials, teprotumumab was effective at improving bulging of the eye, inflammation, double vision and TED-related quality of life. Almost one year after the cessation of treatment, clinical benefits endured in most patients. Teprotumumab was generally well tolerated, with most adverse events being mild or moderate in severity. Adverse events included muscle spasms, hearing loss and hyperglycaemia. Teprotumumab is the first targeted therapy approved for TED and represents an important advance in the management of this condition.