Background/Aim: Medical treatment for Thyroid Eye Disease (TED) has become more specific and targeted as pathophysiology is better understood. Over the last decade, clinical trials informed and led changes in management of TED. This review aimed to explore the efficacy of emerging treatments with a focus on immunotherapies and to summarise future pipelines in new drug trial.
Methods: A narrative review of the literature was performed. Two online databases, Medline and Embase, were searched using keywords for TED, immunotherapy and clinical trials. Inclusion criteria were human clinical trials, immunotherapy, dated from 2012 to 2022 in English. This research also reviewed data from two international clinical trials registries (ClinicalTrials.gov & European Clinical Trials database). Inclusion criteria were current, recruiting, upcoming and completed clinical trials in immunotherapy for TED.
Results: Monoclonal antibodies are increasingly used in the treatment of thyroid eye disease. Teprotumumab has shown significant efficacy in reducing proptosis, inactivation of disease, improving diplopia and quality of life in patients with active TED. Tocilizumab showed superior response in reducing orbital inflammation, especially in steroid resistant cases, while rituximab showed mixed results for TED inactivation. Statins demonstrated early efficacy in improving overall treatment response in combination with intravenous corticosteroid in active TED with hypercholesterolaemia, with a safe side-effect profile. Emerging monoclonal antibodies K1-70 was safe and well tolerated, demonstrated dose dependent induction of hypothyroidism and early evidence of proptosis reduction, while Belimumab showed clinical activity score reduction and favourable side-effect profiles in early phase trial. The novel Long-Circulating PEGylated Liposomal Glucocorticoid also showed significant inflammation improvement without typical steroid side effects. New drug trials targeting novel molecular moiety includes anti-IGF-1R, anti-VEGF-A, anti-neonatal Fc receptor, anti-IL 17A and mTOR inhibitor via subcutaneous and oral formulations are currently underway.
Conclusions: Immunotherapy shows the capability to reduce severity and inflammation in TED, with several large-scale and rigorous studies performed. Therapies in the future will likely involve combination therapies, dosing optimisation and novel/more targeted administration to maximise efficacy and reduce the burden of adverse events.