Abstract Disclosure: G.J. Kahaly: Consulting Fee; Self; Amgen Inc. Research Investigator; Self; Amgen Inc. S.T. Wester: Advisory Board Member; Self; Amgen Inc. Consulting Fee; Self; Immunovant, Lassen. Research Investigator; Self; Amgen Inc, Sling Therapeutics, Immunovant. C.Y. Liu: Other; Self; royalties from Wolters Kluwers Health. H. Kate: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. E. Conrad: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. R.J. Holt: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. Y. Hiromatsu: Advisory Board Member; Self; Amgen Inc. Consulting Fee; Self; Amgen Inc. Research Investigator; Self; Amgen Inc. Introduction: Thyroid eye disease (TED) produces orbital tissue expansion, inflammation, proptosis (eye bulging) and diplopia (double vision), causing eye pain and appearance/visual changes. Teprotumumab, an insulin-like growth factor-1 receptor inhibitor, significantly improved signs and symptoms of TED in three placebo-controlled trials in patients with high inflammation. Here, we report pooled proptosis response in patient subgroups. Methods: Patients ≥18 years old from three placebo-controlled trials, two in the US and EU (NCT01868997, NCT03298867) and one in Japan (OPTIC-J; jRCT2031210453), with Graves’ disease and recent onset (≤9 month duration) active TED (Clinical activity score, CAS≥4, ≥3 for OPTIC-J) were included. Patients received eight infusions of teprotumumab or placebo over 21 weeks, with the final study visit at Week 24 (three weeks after final dose). Observed proptosis response, defined as ≥2 mm improvement from baseline in study eye without deterioration ≥2 mm in fellow eye at Week 24, versus placebo is reported by tobacco use (yes/no), race (White or Asian), and age (<65/≥65). Cochran-Mantel-Haenszel tests compared teprotumumab and placebo subgroups. Results: 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, respectively; mean (SD) TED duration 5.49 (2.32) and 5.98 (2.40) months, respectively; and 78.4% (87) and 73.7% (84) were never/former smokers, respectively. In the overall population, 80.2% (89/111) of teprotumumab patients and 14.0% (16/114) of placebo patients had a proptosis response (P<.0001). At Week 24, 70.8% (17/24) of teprotumumab and 23.3% (7/30) placebo smokers were proptosis responders; in non-smokers, 82.8% (72/87) of teprotumumab and 10.7% (9/84) placebo patients were proptosis responders (P<.0001 for both). In White patients, 78.9% (56/71) of teprotumumab and 15.8% (12/76) of placebo patients were proptosis responders; in Asian patients, 90.0% (27/30) of teprotumumab and 10.0% (3/30) of placebo patients were responders (P<.0001 for both). In patients <65 years, 79.2% (76/96) teprotumumab patients 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). Conclusions: Subgroup analysis of proptosis response by tobacco use, race, and age showed that teprotumumab treatment led to significantly higher proptosis response versus placebo in all groups. Public Presentation: 6/1/2024