Endocrine Abstracts

Graves’ orbitopathy (GO) affects 20-40% of patients with Graves’ disease. Some patients require several treatment modalities with outcomes that are often far from ideal. The quest for disrupting the autoimmune process with targeted therapies began with the emergence of biologics developed for rheumatoid arthritis. In the meantime basic research revealed an important potential role for cross-talk between the TSH and IGF-1 receptors on orbital fibroblasts. This attracted commercial interest, which steamrolled a monoclonal antibody into the GO therapeutic arena. Teprotumumab, an IGF-1 receptor blocker and a failed anti-cancer drug, was revived and repurposed. Thus a new era was born, unveiling unprecedented efficacy in GO including reduction in proptosis and resolution of diplopia. But this came with significant baggage. Unexpected side-effects, a significant relapse rate and an extraordinary high cost. Clinicians in the USA (the only country where the drug is licensed presently) have embraced it and seem to use it widely including for patients with characteristics that were exclusionary in the clinical trials that led to FDA approval. The commercial success of teprotumumab has stimulated interest in the drug development industry and currently several trials are underway in a race to bring competitors to the market. This is good news for patients with GO, but the soaring costs are a concern. The teprotumumab paradigm brings to the forefront two important questions: do endocrinologists have the power to prevent the emergence of GO among their patients with Graves’ disease and bypass the need for astronomically expensive treatments? Do professional organisations have a role in curtailing the greed of the pharmaceutical industry? There is ground to argue that the answer to both questions is yes. Recent guidance from the European and American Thyroid Associations joint Consensus Statement and from the European Group on Graves’ Orbitopathy have provided their valuable perspectives.