Endocrine Abstracts

Objective: Thyroid eye disease (TED) patients may experience pain, proptosis and diplopia. Teprotumumab significantly improved proptosis in three trials in patients with high clinical activity score (CAS), recent-onset TED, and one trial in low CAS, longer-duration TED patients. We report pooled proptosis response in patient subgroups, and across high and low CAS trials.

Methods: Patients ≥18 years from three clinical trials in the US and EU (NCT01868997, NCT03298867) and Japan (OPTIC-J; jRCT2031210453), with Graves’ disease and recent-onset (≤9-month duration) active TED (CAS≥4, ≥3 for OPTIC-J), were included. Patients received eight infusions of teprotumumab or placebo (q3 week dosing) with the final visit at Week-24. Observed proptosis response (≥2 mm improvement) at Week24 is reported by tobacco use (yes/no), race (White/Asian), and age (<65/≥65). Cochran-Mantel-Haenszel (CMH) tests compared teprotumumab vs placebo. Pooled proptosis response rate was calculated across the 3 high CAS trials (above), and one trial in low CAS patients with TED duration ≥2-<10 years (NCT05002998) using CMH adjusted for study and tobacco use status, and non-responder imputation for missing.

Results: In the high CAS, recent-onset TED trials, of 111 teprotumumab and 114 placebo patients, 68.5% (76) and 76.3% (87) were female, respectively; mean (SD) age 50.3 (12.4) and 51.1 (13.1) years; mean (SD) TED duration 5.49 (2.32) and 5.98 (2.40) months; and 78.4% (87) and 73.7% (84) were never/former smokers. At Week-24, in the 3 high CAS trials, 80.2% (89/111) teprotumumab and 14.0% (16/114) placebo patients were proptosis responders (P <.0001). In smokers, 70.8% (17/24) teprotumumab and 23.3% (7/30) placebo patients were proptosis responders; in non-smokers, 82.8% (72/87) teprotumumab and 10.7% (9/84) placebo patients were proptosis responders (P <.0001 for both). In White patients, 78.9% (56/71) teprotumumab and 15.8% (12/76) placebo patients were proptosis responders; in Asian patients, 90.0% (27/30) teprotumumab and 10.0% (3/30) placebo patients were responders (P <.0001 for both). In patients <65 years, 79.2% (76/96) teprotumumab and 13.4% (13/97) placebo patients were responders; in patients ≥65 years, 86.7% (13/15) teprotumumab and 17.6% (3/17) placebo were responders (P <.0001 for both). Across the 4 trials in patients with high and low CAS, 153 and 134 patients received teprotumumab and placebo, respectively. At Week 24, 75.2% (115/153) teprotumumab and 15.7% (21/134) placebo patients were proptosis responders (P <0.0001).

Conclusions: Teprotumumab treatment led to significantly higher proptosis response versus placebo in all subgroups by tobacco use, race and age, and across the trials including patients with high and low CAS.