Advances of IGF-1R Inhibitors in Graves' Ophthalmopathy

Overview

Journal Int Ophthalmol

Specialty Ophthalmology

Date 2024 Nov 22

PMID 39578269

Authors

Meilan Wang

Lian Liu

Affiliations

Soon will be listed here.

Abstract

Graves' ophthalmopathy is the most common extra-thyroidal organ manifestation of Graves' disease. The mainstay of clinical treatment is glucocorticoids; however, side effects and relapse are common problems, and current treatment options cannot alter the disease progression. IGF-1R is an important component of the signaling pathway in Graves' ophthalmopathy, and downstream signaling of IGF-1 and IGF-1R plays a role in many immune-related diseases, possibly leading to disease occurrence through changes in immune phenotype and protein synthesis. Teprotumumab is a human monoclonal antibody targeting the insulin-like growth factor-I receptor (IGF-1R). Clinical trials have shown that teprotumumab reduces proptosis better than placebo, and may be beneficial for patients with worsening disease after steroid cessation. In this review, we discuss the role and prospects of IGF-1R inhibitors in thyroid-associated ophthalmopathy.

References

Yoshida T, Delafontaine P . Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy. Cells. 2020; 9(9). PMC: 7564605. DOI: 10.3390/cells9091970. View

Paik J, Kim S, Kim J, Lee J, Yang S, Lee S . Insulin-like growth factor-1 enhances the expression of functional TSH receptor in orbital fibroblasts from thyroid-associated ophthalmopathy. Immunobiology. 2020; 225(2):151902. DOI: 10.1016/j.imbio.2019.151902. View

Douglas R, Kahaly G, Patel A, Sile S, Thompson E, Perdok R . Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med. 2020; 382(4):341-352. DOI: 10.1056/NEJMoa1910434. View

Lai E, Tai Y, Wu H, Dai Y, Chen T, Cherng Y . The Association between Autoimmune Thyroid Disease and Ocular Surface Damage: A Retrospective Population-Based Cohort Study. J Clin Med. 2023; 12(9). PMC: 10179488. DOI: 10.3390/jcm12093203. View

Bahn R, Heufelder A . Pathogenesis of Graves' ophthalmopathy. N Engl J Med. 1993; 329(20):1468-75. DOI: 10.1056/NEJM199311113292007. View

Bartalena L, Kahaly G, Baldeschi L, Dayan C, Eckstein A, Marcocci C . The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021; 185(4):G43-G67. DOI: 10.1530/EJE-21-0479. View

Smith T, Bartalena L . Will biological agents supplant systemic glucocorticoids as the first-line treatment for thyroid-associated ophthalmopathy?. Eur J Endocrinol. 2019; 181(5):D27-D43. PMC: 7398270. DOI: 10.1530/EJE-19-0389. View

Sisti E, Coco B, Menconi F, Leo M, Rocchi R, Latrofa F . Intravenous glucocorticoid therapy for Graves' ophthalmopathy and acute liver damage: an epidemiological study. Eur J Endocrinol. 2015; 172(3):269-76. DOI: 10.1530/EJE-14-0712. View

Wiersinga W . Advances in treatment of active, moderate-to-severe Graves' ophthalmopathy. Lancet Diabetes Endocrinol. 2016; 5(2):134-142. DOI: 10.1016/S2213-8587(16)30046-8. View

10.

Smith T, Hegedus L . Graves' Disease. N Engl J Med. 2016; 375(16):1552-1565. DOI: 10.1056/NEJMra1510030. View

11.

Bahn R . Graves' ophthalmopathy. N Engl J Med. 2010; 362(8):726-38. PMC: 3902010. DOI: 10.1056/NEJMra0905750. View

12.

Kumar S, Nadeem S, Stan M, Coenen M, Bahn R . A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Graves' ophthalmopathy. J Mol Endocrinol. 2011; 46(3):155-63. PMC: 3074639. DOI: 10.1530/JME-11-0006. View

13.

Moshkelgosha S, So P, Deasy N, Diaz-Cano S, Banga J . Cutting edge: retrobulbar inflammation, adipogenesis, and acute orbital congestion in a preclinical female mouse model of Graves' orbitopathy induced by thyrotropin receptor plasmid-in vivo electroporation. Endocrinology. 2013; 154(9):3008-15. DOI: 10.1210/en.2013-1576. View

14.

Douglas R, Afifiyan N, Hwang C, Chong K, Haider U, Richards P . Increased generation of fibrocytes in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab. 2009; 95(1):430-8. PMC: 2805489. DOI: 10.1210/jc.2009-1614. View

15.

Smith T, Janssen J . Insulin-like Growth Factor-I Receptor and Thyroid-Associated Ophthalmopathy. Endocr Rev. 2018; 40(1):236-267. PMC: 6338478. DOI: 10.1210/er.2018-00066. View

16.

Ferrari S, Paparo S, Ragusa F, Elia G, Mazzi V, Patrizio A . Chemokines in thyroid autoimmunity. Best Pract Res Clin Endocrinol Metab. 2023; 37(2):101773. DOI: 10.1016/j.beem.2023.101773. View

17.

George A, Diana T, Langericht J, Kahaly G . Stimulatory Thyrotropin Receptor Antibodies Are a Biomarker for Graves' Orbitopathy. Front Endocrinol (Lausanne). 2021; 11:629925. PMC: 7885640. DOI: 10.3389/fendo.2020.629925. View

18.

Rotondo Dottore G, Torregrossa L, Caturegli P, Ionni I, Sframeli A, Sabini E . Association of T and B Cells Infiltrating Orbital Tissues With Clinical Features of Graves Orbitopathy. JAMA Ophthalmol. 2018; 136(6):613-619. PMC: 6583879. DOI: 10.1001/jamaophthalmol.2018.0806. View

19.

Wang Y, Chen Z, Wang T, Guo H, Liu Y, Dang N . A novel CD4+ CTL subtype characterized by chemotaxis and inflammation is involved in the pathogenesis of Graves' orbitopathy. Cell Mol Immunol. 2021; 18(3):735-745. PMC: 8027210. DOI: 10.1038/s41423-020-00615-2. View

20.

Wissmiller K, Bilekova S, Franko A, Lutz S, Katsburg M, Gulde S . Inceptor correlates with markers of prostate cancer progression and modulates insulin/IGF1 signaling and cancer cell migration. Mol Metab. 2023; 71:101706. PMC: 10074927. DOI: 10.1016/j.molmet.2023.101706. View