Endocrine Abstracts

Objectives: Teprotumumab, an IGF1-receptor antagonist, has been shown in three clinical trials to markedly improve the clinical course of Thyroid Eye Disease (TED) or Graves’ Orbitopathy (GO) with significant improvements noted in inflammation, proptosis, and diplopia. Furthermore, compared to placebo moderate-to-large improvements were noted in the total, appearance (AP), and visual function (VF) as measured by EUGOGO GO quality of life (GO-QOL) scores after 24 weeks of therapy. Based on these findings, we undertook an analysis to determine the major outcomes associated with these substantial changes in QOL.

Methods: A total of 120 patients with moderate-to-severe TED who were treated with teprotumumab from the phase 2, phase 3 (OPTIC), and OPTIC-X controlled studies were examined with observation points on study day 1, week 6, 12, and 24. Linear mixed-effects models were employed to measure the impact of Demographics, Time on treatment, Proptosis (mm), Diplopia (Gorman Grade), presence/absence of Gaze Evoked Orbital Pain, and Spontaneous Orbital Pain on Total, AP, and VF GO-QOL scores, via hierarchical addition. Random effects accounted for within-patient response variability.

Results: Mean age was 52 (SD 12) years and females represented 73% of the population examined. Total, AP and VF GO-QOL scores improved 27%, 33%, and 23% respectively from baseline to Week-24. Patients with proptosis improved Total, AP and VF GO-QOL by 44%, 37%, and 49% respectively. The final model indicated that within-patient variability accounted for 80% of Total GO-QOL Score variance. Improvements in Diplopia and Gazed Evoked Orbital Pain were significantly related to higher (improved) Total, AP, and VF scores (P < 0.001 for all). Improvements in Spontaneous Orbital Pain were associated with higher Total and VF scores (P < 0.001). Increasing age (P < 0.001) and male sex (P = 0.02) had a significant positive correlation with the AP Score. All scores were positively associated with time on study (P < 0.001). Gazed Evoked Orbital Pain and Proptosis were found to interact significantly, such that an improvement in proptosis correlated to a greater improvement in the AP score in patients without Gaze Evoked Orbital Pain as compared with those that had Gaze Evoked Orbital Pain(P < 0.001).

Conclusions: These novel data indicate that improvement in Diplopia and orbital pain, particularly Gaze Evoked Orbital Pain are strong contributors to GO-QOL improvement in TED patients receiving teprotumumab. Gaze Evoked Orbital Pain may impact patients’ perception of AP improvements through its interaction with proptosis reduction.