Abstract
Purpose
Teprotumumab, a blocking antibody to the insulin like growth factor 1 receptor (IGF-1R) has been shown to significantly reduce proptosis in recent phase 2 and 3 trials in patients with inflammatory thyroid eye disease (TED). Herein, we investigate the impact of teprotumumab on patients with non-inflammatory TED. We also investigate the expression of the IGF-1R on orbital tissues from patients with inflammatory and non-inflammatory TED compared to controls.
Methods
Consecutive patients with non-inflammatory TED (clinical activity score, CAS ≤ 1, for at least 4 months, were treated with teprotumumab. They received a complete course (total eight infusions) of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for subsequent infusions every 3 weeks). The primary outcome was a proptosis response at week 24. Further, IGF-1R α and β expression was evaluated on orbital tissue from patients with inflammatory and non-inflammatory TED, as well as healthy controls. Non-biased histological analysis of IGF-1R expression was performed using ImageJ.
Results
Four patients met eligibility criteria for the clinical study, with a mean (SD) CAS of 0 (0). Following teprotumumab treatment, there was a mean (SD) reduction in proptosis of 2.6 mm (1.2). Five patients were included for each group of the histological study; inflammatory TED, non-inflammatory TED and controls. IGF-1Rα and IGF-1Rβ expression was significantly greater in the orbital tissues of patients with inflammatory TED and non-inflammatory TED, when compared to controls.
Conclusion
Our findings demonstrate for the first time, that teprotumumab, a blocking antibody to the IGF-1R reduces proptosis in a series of patients with non-inflammatory TED. Overexpression of the IGF-1R in orbital tissue from patients with non-inflammatory disease compared to controls may be an important consideration for effect.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Bahn RS. Graves’ ophthalmopathy. N Engl J Med. 2010;362:726–38.
Ugradar S, Rootman DB. Case Series. Ophthal Plast Reconstr Surg 2018:1. http://insights.ovid.com/crossref?an=00002341-900000000-98532. Accessed 27 Mar 2018.
Mourits MP, Koornneef L, Wiersinga WM, et al. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: a novel approach. Br J Ophthalmol. 1989;73:639–44.
Kim JW, Woo YJ, Yoon JS. Is modified clinical activity score an accurate indicator of diplopia progression in Graves’ orbitopathy patients? Endocr J. 2016;63:1133–40. http://www.ncbi.nlm.nih.gov/pubmed/27628269. Accessed 5 Jan 2018.
Ugradar S, Rootman DB Case Series. Ophthal Plast Reconstr Surg 2018:1. http://www.ncbi.nlm.nih.gov/pubmed/29465483. Accessed 28 Feb 2018.
Bartalena L, Krassas GE, Wiersinga W, et al. Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab. 2012;97:4454–63.
DPF L, S R, M B, et al. Low dose of rituximab for corticosteroid-resistant graves’ orbitopathy. Eur Thyroid J. 2014;3:110. http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L71947247%0Ahttp://dx.doi.org/10.1159/000365244%0Ahttp://sfx.library.uu.nl/utrecht?sid=EMBASE&issn=22350640&id=doi:10.1159%2F000365244&atitle=Low+dose+of+rituximab+for+corticosteroid
Kahaly GJ, Riedl M, König J, et al. Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves’ orbitopathy (MINGO): a randomised, observer-masked, multicentre trial. Lancet Diabetes Endocrinol. 2018;6:287–98.
Rajendram R, Taylor PN, Wilson VJ, et al. Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 2018;6:299–309.
Tsui S, Naik V, Hoa N, et al. 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;181:4397–405.
Pritchard J, Horst N, Cruikshank W, Smith TJ. Igs from patients with Graves’ disease induce the expression of T cell chemoattractants in their fibroblasts. J Immunol. 2002;168:942–50.
Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376:1748–61.
Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382:341–52.
Smith TJ, 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;89:5076–80.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
RD—Consultant Horizon Therapeutics, Immunovant Corporation. The other authors declare that they have no conflict of interest.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ugradar, S., Shi, L., Wang, Y. et al. Teprotumumab for non-inflammatory thyroid eye disease (TED): evidence for increased IGF-1R expression. Eye 35, 2607–2612 (2021). https://doi.org/10.1038/s41433-020-01297-w
Received:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41433-020-01297-w
This article is cited by
-
Comparative efficacy and safety of rituximab, tocilizumab, and teprotumumab in Graves’ orbitopathy: a systematic review and meta-analysis
Eye (2025)
-
The Use of Biologics for Thyroid Eye Disease
BioDrugs (2025)
-
Teprotumumab for thyroid eye disease in patients with hypothyroid/euthyroid state: a multicenter case series
Graefe's Archive for Clinical and Experimental Ophthalmology (2025)
-
Data mining and analysis of adverse event signals associated with teprotumumab using the Food and Drug Administration adverse event reporting system database
International Journal of Clinical Pharmacy (2024)
-
Teprotumumab improves light sensitivity in patients with thyroid eye disease
Graefe's Archive for Clinical and Experimental Ophthalmology (2024)
