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.