Teprotumumab As a Novel Therapy for Thyroid-Associated Ophthalmopathy

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2021 Jan 4

PMID 33391187

Citations 2

Authors

Terry J Smith

Affiliations

Soon will be listed here.

Abstract

Thyroid-associated ophthalmopathy (TAO) has remained a vexing and poorly managed autoimmune component of Graves' disease where the tissues surrounding the eye and in the upper face become inflamed and undergo remodeling. This leads to substantial facial disfigurement while in its most severe forms, TAO can threaten eye sight. In this brief paper, I review some of the background investigation that has led to development of teprotumumab as the first and only US FDA approved medical therapy for TAO. This novel treatment was predicated on recognition that the insulin-like growth factor I receptor plays an important role in the pathogenesis of TAO. It is possible that a similar involvement of that receptor in other autoimmune disease may lead to additional indications for this and alternative insulin-like growth factor I receptor-inhibiting strategies.

Citing Articles

MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy.

Tang W, Lv Q, Huang X, Li Y, Zou J, Zheng J J Inflamm Res. 2022; 15:1543-1554.

PMID: 35256853 PMC: 8898058. DOI: 10.2147/JIR.S339483.

Infusion Center Guidelines for Teprotumumab Infusions: Informed Consent, Safety, and Management of Side Effects.

Kang J, Lechuga M, Braun J, Kossler A, Douglas R, Cockerham K J Infus Nurs. 2021; 44(6):331-338.

PMID: 34753152 PMC: 10853843. DOI: 10.1097/NAN.0000000000000446.

References

Pritchard J, Han R, Horst N, Cruikshank W, Smith T . Immunoglobulin activation of T cell chemoattractant expression in fibroblasts from patients with Graves' disease is mediated through the insulin-like growth factor I receptor pathway. J Immunol. 2003; 170(12):6348-54. DOI: 10.4049/jimmunol.170.12.6348. View

Smith T, Hoa N . Immunoglobulins from patients with Graves' disease induce hyaluronan synthesis in their orbital fibroblasts through the self-antigen, insulin-like growth factor-I receptor. J Clin Endocrinol Metab. 2004; 89(10):5076-80. DOI: 10.1210/jc.2004-0716. View

Tsui S, Naik V, Hoa N, Hwang C, Afifiyan N, Hikim A . Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in Graves' disease. J Immunol. 2008; 181(6):4397-405. PMC: 2775538. DOI: 10.4049/jimmunol.181.6.4397. View

Wang H, Cao H, Winn V, Rezanka L, Frobert Y, Evans C . Leukoregulin induction of prostaglandin-endoperoxide H synthase-2 in human orbital fibroblasts. An in vitro model for connective tissue inflammation. J Biol Chem. 1996; 271(37):22718-28. View

Jones J, Clemmons D . Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995; 16(1):3-34. DOI: 10.1210/edrv-16-1-3. View

Fernando R, Lu Y, Atkins S, Mester T, Branham K, Smith T . Expression of thyrotropin receptor, thyroglobulin, sodium-iodide symporter, and thyroperoxidase by fibrocytes depends on AIRE. J Clin Endocrinol Metab. 2014; 99(7):E1236-44. PMC: 4079309. DOI: 10.1210/jc.2013-4271. View

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

Heufelder A, Dutton C, Sarkar G, Donovan K, Bahn R . Detection of TSH receptor RNA in cultured fibroblasts from patients with Graves' ophthalmopathy and pretibial dermopathy. Thyroid. 1993; 3(4):297-300. DOI: 10.1089/thy.1993.3.297. View

Raychaudhuri N, Fernando R, Smith T . Thyrotropin regulates IL-6 expression in CD34+ fibrocytes: clear delineation of its cAMP-independent actions. PLoS One. 2013; 8(9):e75100. PMC: 3783445. DOI: 10.1371/journal.pone.0075100. View

10.

Sadagurski M, White M . Integrating metabolism and longevity through insulin and IGF1 signaling. Endocrinol Metab Clin North Am. 2013; 42(1):127-48. PMC: 3982789. DOI: 10.1016/j.ecl.2012.11.008. View

11.

Marcocci C, Bartalena L, Panicucci M, Marconcini C, Cartei F, Cavallacci G . Orbital cobalt irradiation combined with retrobulbar or systemic corticosteroids for Graves' ophthalmopathy: a comparative study. Clin Endocrinol (Oxf). 1987; 27(1):33-42. DOI: 10.1111/j.1365-2265.1987.tb00836.x. View

12.

Fang S, Huang Y, Liu X, Zhong S, Wang N, Zhao B . Interaction Between CCR6+ Th17 Cells and CD34+ Fibrocytes Promotes Inflammation: Implications in Graves' Orbitopathy in Chinese Population. Invest Ophthalmol Vis Sci. 2018; 59(6):2604-2614. DOI: 10.1167/iovs.18-24008. View

13.

Smith T, Sempowski G, Wang H, Del Vecchio P, Lippe S, Phipps R . Evidence for cellular heterogeneity in primary cultures of human orbital fibroblasts. J Clin Endocrinol Metab. 1995; 80(9):2620-5. DOI: 10.1210/jcem.80.9.7673404. View

14.

Smith T, Kahaly G, Ezra D, Fleming J, Dailey R, Tang R . Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med. 2017; 376(18):1748-1761. PMC: 5718164. DOI: 10.1056/NEJMoa1614949. View

15.

Han R, Chen B, Smith T . Jak2 dampens the induction by IL-1beta of prostaglandin endoperoxide H synthase 2 expression in human orbital fibroblasts: evidence for divergent influence on the prostaglandin E2 biosynthetic pathway. J Immunol. 2007; 179(10):7147-56. DOI: 10.4049/jimmunol.179.10.7147. View

16.

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

17.

Douglas R, Gianoukakis A, Kamat S, Smith T . Aberrant expression of the insulin-like growth factor-1 receptor by T cells from patients with Graves' disease may carry functional consequences for disease pathogenesis. J Immunol. 2007; 178(5):3281-7. DOI: 10.4049/jimmunol.178.5.3281. View

18.

Pilling D, Fan T, Huang D, Kaul B, Gomer R . Identification of markers that distinguish monocyte-derived fibrocytes from monocytes, macrophages, and fibroblasts. PLoS One. 2009; 4(10):e7475. PMC: 2759556. DOI: 10.1371/journal.pone.0007475. View

19.

Ozzello D, Kikkawa D, Korn B . Early experience with teprotumumab for chronic thyroid eye disease. Am J Ophthalmol Case Rep. 2020; 19:100744. PMC: 7243051. DOI: 10.1016/j.ajoc.2020.100744. View

20.

Hwa V, Oh Y, Rosenfeld R . The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocr Rev. 1999; 20(6):761-87. DOI: 10.1210/edrv.20.6.0382. View