Outcomes
VF, diplopia, TED, −2.41, Graves’ Ophthalmopathy, proptosis, SE, visual function).A
DIPLOPIA, PROPTOSIS
The primary endpoint was met. At Week 24, in the ITT population, least squares (LS) mean (SE) change in proptosis from baseline in teprotumumab group was −2.41 (0.23) mm vs −0.92 (0.32) mm in the placebo group (between-group difference, −1.48 mm; 95% CI −2.28, −0.69; A, LS Mean change from baseline in proptosis in mm (primary endpoint, ITT, MMRM). B, LS Mean change from baseline in proptosis in mm (per protocol, MMRM). C, percentage of patients with a proptosis response (ITT). D, percentage of patients with a proptosis response (per protocol). LS Mean change from baseline in the (E) GO-QOL Visual Function subscale and (F) GO-QOL Appearance-related subscale (MMRM). Error bars represent 95% CI. Abbreviations: AP, appearance subscale; BL, baseline; GO-QOL, Graves’ Ophthalmopathy Quality of Life questionnaire; LS, least squares; MMRM, mixed model for repeated measures, VF, visual function subscale.Significantly greater improvements from baseline were observed with teprotumumab vs placebo at Week 24 in the GO-QOL Visual Function subscale: LS mean (SE) 8.73 (1.661) vs 2.41 (2.329), respectively, with treatment difference 6.31 (95% CI 0.57, 12.06, A small number of enrolled patients had diplopia at baseline and the proportions were unevenly matched in the teprotumumab (14/42, 33%) and placebo arms (4/20, 20%). Improvements in diplopia were not significant for teprotumumab vs placebo: Of patients with diplopia at baseline, 6/14 (42.9%) patients in the teprotumumab group had an improvement of ≥ 1 grade in diplopia, vs 2/4 (50%) patients in the placebo group. Four of 14 (28.6%) in the teprotumumab group vs 1/4 (25%) in the placebo group had complete resolution of diplopia at Week 24. Using the proportional odds model with diplopia reported as ordinal response categories, the odds ratio for change from baseline at Week 24 favored teprotumumab but was not significant (2.13; 95% CI 0.39, 11.60; For 6 patients (12 eyes) in the teprotumumab group who had orbital MRI at baseline and Week 24, an improvement in proptosis was accompanied by a mean decrease from baseline in retro-orbital total muscle volume of 24.95%, with mean volume decrease of 24.31% in the inferior rectus, 20.07% in the superior rectus, 15.1% in the medial rectus, and 28.85% in the lateral rectus. A mean decrease in orbital fat volume of 34.63% was observed (A, Patient characteristics and reduction in orbital muscle and fat volume in 6 patients (study eye and fellow eye) in the teprotumumab group. B, MRI at baseline and Week 24 in an individual patient (#5 in panel A) treated with teprotumumab. The green circle indicates the superior rectus and the blue circle indicates the inferior rectus of the study eye. The patient was female, aged 64 with approximately 7 years since diagnosis of TED and no diplopia at baseline. At Week 24, proptosis was reduced in the study eye and fellow eye by 3 and 2.5 mm, respectively and GO-QOL improved by 49 (overall), 75 (appearance), and 23 (visual function).A, Reduction in volume of each orbital muscle and fat for 6 patients (12 eyes) with MRI imaging at baseline and Week 24. B, GO-QOL overall, appearance, and visual function scores in the 6 patients with MRI imaging. C, muscle and fat volumes at baseline and Week 24 in an individual patient (#5 in 