Teprotumumab for non-inflammatory thyroid eye disease (TED): evidence for increased IGF-1R expression.

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.

• Authors: Shoaib Ugradar, Lu Shi, Yao Wang, Tunde Mester, Huasheng Yang, Raymond S Douglas
• Journal: Eye (London, England) (Eye (Lond)) Vol. 35 Issue 9 Pg. 2607-2612 (09 2021) ISSN: 1476-5454 [Electronic] England
• PMID: 33221815 (Publication Type: Journal Article)
• Copyright: © 2020. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.

Chemical References

• Antibodies, Monoclonal, Humanized
• teprotumumab

Topics

• Antibodies, Monoclonal, Humanized
• Exophthalmos (drug therapy)
• Graves Ophthalmopathy (drug therapy)
• Humans