Endocrine Abstracts

Background: Teprotumumab showed significant improvements vs placebo for the treatment of thyroid eye disease (TED) in clinical trials1,2 and is approved in the United States (US) but currently not in the EU. Differences exist in baseline patient demographics and characteristics between EU and US patients. Here we examine outcomes in these 2 cohorts.

Methods: Data from the EU and US sites for patients in the teprotumumab group (n =121) from the integrated randomized, double-masked, placebo-controlled 24-week phase 2 and 3 trials and open label OPTIC-X trial (first time teprotumumab treated patients) were analyzed. The primary outcome was proptosis reduction of ≥2 mm from baseline (BL). Secondary outcomes were diplopia response (improvement from BL in diplopia of ≥1 grade [Gorman scale]), Clinical Activity Score (CAS) of 0 or 1, an Overall response (reduction of ≥2 in CAS plus reduction in proptosis of ≥2 mm), the least squares (LS) and mean BL change in proptosis (mm) and LS and mean change in Graves’ ophthalmopathy-specific quality-of-life (GO-QOL) score. Tobacco exposure was controlled for using a mixed-model repeated-measures analysis with an unstructured covariance matrix.

Results: There were a total of 54 and 67 teprotumumab- treated patients in the EU and US, respectively. Tobacco use was 38.9% in EU vs 10.4% in US. More EU teprotumumab patients were white compared with US (96.3% vs 77.6%). Months since diagnosis of Graves’ disease was longer in EU than US (43.8 vs 30.1). Fewer EU patients had constant diplopia (grade 3) at BL than US (18.5% vs 34.3%). At week 24, all the primary and secondary outcomes in EU teprotumumab-treated patients were not significantly different from US teprotumumab treated patients including proptosis response (83.3% [45/54] vs. 79.1% [53/67], P = 0.591), diplopia response (60.0% [24/40] vs. 73.5% [36/49], P = 0.428), CAS 0/1 (70.6% [36/51] vs. 56.9% [37/65], P = 0.357), overall response (78.4% [40/51] vs. 72.3% [47/65], P = 0.447), LS mean change in proptosis of −3.28 mm vs. −3.23 mm, P = 0.876, BL mean change in proptosis of -3.22 mm vs.-3.39 mm at Week 24; and LS mean change in GO-QOL overall score of 16.54 points vs. 16.65 points, P = 0.974 with BL mean change in GO-QOL of 15.9 vs. 18.32 at Week 24.

Conclusions: Despite some differences in patient characteristics at BL, EU teprotumumab treated patients had no significant difference in efficacy outcomes with respect to proptosis, CAS, diplopia, overall response, and quality of life as compared with US teprotumumab treated patients.