gms | German Medical Science

Introduction: Thyroid eye disease (TED) can cause proptosis, diplopia, eye pain and changes in appearance and vision. 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 trials, two in the US and EU (NCT01868997, NCT03298867) and one in Japan (OPTIC-J; jRCT2031210453), with TED onset ≤9 months, Clinical activity score, CAS≥4, ≥3 for OPTIC-J) were included. Patients received eight infusions of teprotumumab or placebo over 24 weeks. 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.