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Background Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of active Thyroid eye disease (TED). The current study reviews its efficacy in chronic TED. Methods In this retrospective review, consecutive patients with chronic stable TED (>2 years), who had received ≥3 infusions of teprotumumab were included. All patients had measurements of proptosis, and calculation of the CAS and diplopia scores before and after therapy. Five-point strabismus scores were also calculated. Patients who had imaging within 4 months prior to therapy and 6 weeks post therapy underwent orbital 3D volumetric analysis. Results Thirty-one patients met the inclusion criteria. The mean (SD) duration of TED was 81 months (56) and the mean (SD) number of infusions received by each patient was 7 (2). Mean (SD) reduction in proptosis for each study orbit was 3.5 mm (0.4) and 3 mm (0.3) for the fellow orbit. The CAS response was 90% for the study orbit and 87% for the fellow orbit. Of the 15 patients who had diplopia at baseline, 67% had a clinically significant response, while 47% had complete resolution following treatment. Following teprotumumab, mean (SD) reduction of muscle tissue was 2011 mm3 (1847) in the study orbit and 1620 mm3 (1759) in the fellow orbit. The mean (SD) reduction of fat volume was 2101 mm3 (1681) in the study orbit and 1370 mm3 (1181) in the fellow orbit. Conclusion Teprotumumab significantly reduces proptosis, inflammation, diplopia, strabismus and orbital soft tissue volume in patients with chronic TED.
PurposeThyroid eye disease (TED) is a progressive, debilitating and potentially vision-threatening autoimmune disease. Teprotumumab, a novel human monoclonal antibody, has been shown to reverse the clinical manifestations of TED. Patients receiving teprotumumab have been shown in two multicenter, randomized placebo-controlled trials to have decreased proptosis, diplopia and inflammation after 24 weeks of treatment. This study aims to analyse volumetric and inflammatory changes on orbital imaging prior to and after teprotumumab treatment from one of these trials.DesignRetrospective review.SubjectsSix patients enrolled in the phase III teprotumumab clinical trial (OPTIC, NCT03298867) with active TED who received 24 weeks of teprotumumab and had pre- and post-treatment orbital imaging (CT or MRI). Additionally, 12 non-TED patients (24 orbits) were analysed as a comparative control group.Methods3D volumetric calculations of the extraocular muscles (EOMs), orbital fat, and bony orbit were measured using previously validated image processing software. 3D volumetric results and changes in EOM inflammation were compared with clinical measurements of TED.ResultsTotal EOM volume within each orbit was markedly reduced post-teprotumumab in all patients (n=six patients, 12/12 orbits, p<0.02). There was no statistical difference in post-treatment EOM volume when compared to non-TED controls. Total orbital fat volume was also reduced in 11 of 12 studied orbits (n=six patients, p=0.04). Overall EOM inflammation based on MRI signal intensity ratio was reduced in 8/8 orbits (n=four patients, p<0.01).ConclusionOrbital imaging demonstrated decreased EOM volumes and orbital fat tissue volumes after teprotumumab treatment.
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.
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