Alan Chun Hong Lee1,2, George J Kahaly2. 1. Division of Endocrinology and Metabolism, Department of Medicine, Queen Mary Hospital, Hong Kong, China. 2. Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany.
Abstract
BACKGROUND: Both Graves' hyperthyroidism (GH) and Graves' orbitopathy (GO) are associated with significant adverse health consequences. All conventional treatment options have limitations regarding efficacy and safety. Most importantly, they do not specifically address the underlying immunological mechanisms. We aim to review the latest development of treatment approaches in these two closely related disorders. SUMMARY: Immunotherapies of GH have recently demonstrated clinical efficacy in preliminary studies. They include ATX-GD-59, an antigen-specific immunotherapy which restores immune tolerance to the thyrotropin receptor; iscalimab, an anti-CD40 monoclonal antibody which blocks the CD40-CD154 costimulatory pathway in B-T cell interaction; and K1-70, a thyrotropin receptor-blocking monoclonal antibody. Novel treatment strategies have also become available in GO. Mycophenolate significantly increased the overall response rate combined with standard glucocorticoid (GC) treatment compared to GC monotherapy. Tocilizumab, an anti-interleukin 6 receptor monoclonal antibody, displayed strong anti-inflammatory action in GC-resistant cases. Teprotumumab, an anti-insulin-like growth factor 1 receptor monoclonal antibody, resulted in remarkable improvement in terms of disease activity, proptosis, and diplopia. Further, rituximab appears to be useful in active disease of recent onset without impending dysthyroid optic neuropathy. KEY MESSAGES: Therapeutic advances will continue to optimize our management of GH and associated orbitopathy in an effective and safe manner.
BACKGROUND: Both Graves' hyperthyroidism (GH) and Graves' orbitopathy (GO) are associated with significant adverse health consequences. All conventional treatment options have limitations regarding efficacy and safety. Most importantly, they do not specifically address the underlying immunological mechanisms. We aim to review the latest development of treatment approaches in these two closely related disorders. SUMMARY: Immunotherapies of GH have recently demonstrated clinical efficacy in preliminary studies. They include ATX-GD-59, an antigen-specific immunotherapy which restores immune tolerance to the thyrotropin receptor; iscalimab, an anti-CD40 monoclonal antibody which blocks the CD40-CD154 costimulatory pathway in B-T cell interaction; and K1-70, a thyrotropin receptor-blocking monoclonal antibody. Novel treatment strategies have also become available in GO. Mycophenolate significantly increased the overall response rate combined with standard glucocorticoid (GC) treatment compared to GC monotherapy. Tocilizumab, an anti-interleukin 6 receptor monoclonal antibody, displayed strong anti-inflammatory action in GC-resistant cases. Teprotumumab, an anti-insulin-like growth factor 1 receptor monoclonal antibody, resulted in remarkable improvement in terms of disease activity, proptosis, and diplopia. Further, rituximab appears to be useful in active disease of recent onset without impending dysthyroid optic neuropathy. KEY MESSAGES: Therapeutic advances will continue to optimize our management of GH and associated orbitopathy in an effective and safe manner.
Authors: Terry J Smith; George J Kahaly; Daniel G Ezra; James C Fleming; Roger A Dailey; Rosa A Tang; Gerald J Harris; Alessandro Antonelli; Mario Salvi; Robert A Goldberg; James W Gigantelli; Steven M Couch; Erin M Shriver; Brent R Hayek; Eric M Hink; Richard M Woodward; Kathleen Gabriel; Guido Magni; Raymond S Douglas Journal: N Engl J Med Date: 2017-05-04 Impact factor: 91.245
Authors: Carlos A Canas; Fabio Bonilla-Abadia; Katherine Vallejo; Hector M Rengifo; Marco A Gallon; Gabriel J Tobon Journal: Endocr Metab Immune Disord Drug Targets Date: 2018 Impact factor: 2.895