Possibilities and prospects of targeted therapy with monoclonal antibodies for endocrine ophthalmopathy

D.S. Atarshchikov¹, E.S. Taskina²

¹N.I. Pirogov Russian National Research Medical University, Moscow, Russian Federation

²Chita State Medical University, Chita, Russian Federation

Endocrine ophthalmopathy (EO) is an autoimmune disorder affecting the extraocular muscles and/or retrobulbar adipose tissue, which commonly develops in the context of thyroid dysfunction. Conventional therapeutic approaches, including nonspecific immunosuppression with high-dose glucocorticoids, orbital radiotherapy, and complex surgical interventions, are commonly associated with limited efficacy and a significant risk of adverse events. Over the past decade, significant advances in the understanding of EO pathogenesis have opened new avenues for treatment, namely, targeted therapy using monoclonal antibodies. The aim of this study was to conduct a comparative analysis of published data describing pathogenetic mechanisms, efficacy, safety, and long-term outcomes of targeted therapy with monoclonal antibodies in EO. A systematic review of contemporary literature was conducted using PubMed, Scopus, MEDLINE, Cochrane Library, and eLibrary databases for the period from January 2005 to May 2025. The search strategy included combinations of the following keywords: endocrine ophthalmopathy, pathogenesis, targeted therapy, monoclonal antibodies, teprotumumab, rituximab, tocilizumab, efficacy, safety. The initial search yielded 563 results. Following removal of duplicates and screening based on inclusion criteria (originality, relevance to the topic of targeted therapy in EO, and availability), 50 publications were selected for detailed analysis. This review compares studies assessing targeted therapy of EO using monoclonal antibodies directed against the insulin-like growth factor 1 receptor (teprotumumab), cluster of differentiation 20 (CD20) (rituximab), and interleukin-6 (tocilizumab). Among these, teprotumumab currently has the most robust evidence base for efficacy (particularly in regard to improvement of diplopia) and has been approved as a first-line therapy for active moderate-to-severe EO in the United States. Despite its strong evidentiary support, teprotumumab does not currently have regulatory approval from the Ministry of Health of the Russian Federation. The use of rituximab has produced conflicting results, leading to its restricted use. Tocilizumab therapy has demonstrated promising clinical efficacy (in terms of reduced disease activity and proptosis) and an acceptable safety profile, especially in patients with glucocorticoid-refractory EO; however, confirmation in large randomized clinical trials is required. Other targeted agents (belimumab, infliximab, adalimumab, secukinumab, aflibercept, etc.) remain under active study. Advances in the understanding of EO pathogenesis have enabled a shift from conventional nonspecific treatments to promising targeted therapy with monoclonal antibodies, which act on key elements of the immune response and provide new perspectives for more effective and safer management of this disease.

Keywords: endocrine ophthalmopathy, pathogenesis, targeted therapy, monoclonal antibodies, teprotumumab, rituximab, tocilizumab, efficacy, safety.

For citation: Atarshchikov D.S., Taskina E.S. Possibilities and prospects of targeted therapy with monoclonal antibodies for endocrine ophthalmopathy. Russian Journal of Clinical Ophthalmology. 2025;25(3):222–230 (in Russ.). DOI: 10.32364/2311-7729-2025-25-3-10