Monoclonal Antibodies for the Treatment of Graves Orbitopathy: Precision Medicine?

Abstract

Purpose: To summarize the development, nomenclature, and rationale of the reported use of monoclonal antibodies (Mabs) in Graves Orbitopathy (GO) and to undertake a systematic review of the management of GO with Mabs. Methods: The Pubmed and Embase databases and the Federal Brazilian searching site (Periódicos-CAPES) were screened. The authors searched all the keywords “monoclonal antibodies,” “adalimumab,” “belimumab,” “infliximab,” “rituximab,” “teprotumumab,” and “tocilizumab” combined with the terms “Graves Orbitopathy,” “Graves eye disease” and “thyroid eye disease.” All the articles published in English, French, and Spanish from 2000 to May 2022 were screened. Only publications with quantitative data on the activity of orbitopathy, proptosis, or both were included. Results: Seventy-six articles of the 954 screened records met the inclusion criteria. Seven Mabs were described for treating GO. The three most reported Mabs were Rituximab, Tocilizumab, and Teprotumumab. Only eight randomized clinical trials compared the effect of these three Mabs and Belimumab with the effect of steroids or placebos. Adalimumab, Infliximab, and K1-70 only appeared in a few case series and case reports. Frequent mild-to-moderate and few major side effects occurred with the three most used Mabs. Relapse rates ranged from 7.4% for Tocilizumab to at least 29.4% for Teprotumumab. No randomized clinical trials compared Mabs head-to-head. Conclusion: Considering the lack of head-to-head comparisons between Mabs, the relapse rate, the possibility of severe collateral effects, and the cost of Mabs, it is not clear which Mab is the safest and most useful to treat GO.

Efficiency and Safety of Tocilizumab for the Treatment of Thyroid Eye Disease: A Systematic Review

“…[10][11][12][13] These infiltrating cells activate and induce resident fibroblasts to produce several TED-relevant cytokines, secrete extracellular matrix components including hyaluronic acid, mucopolysaccharide, and glycosaminoglycan, and increase their proliferative activity and differentiation into adipocytes and myofibroblasts. 10,14 TED is a self-limited condition in which spontaneous resolution is common, and the choice of treatment depends on the phase of the disease. The initial acute inflammatory or active phase is manifested by eyelid retraction, proptosis, eyelid and conjunctival hyperemia, pain, and chemosis.…”

“…10–13 These infiltrating cells activate and induce resident fibroblasts to produce several TED-relevant cytokines, secrete extracellular matrix components including hyaluronic acid, mucopolysaccharide, and glycosaminoglycan, and increase their proliferative activity and differentiation into adipocytes and myofibroblasts. 10,14…”