OPTIC-X Study: teprotumumab use as retreatment and in longer duration thyearoid eye disease (TED)

Douglas, R. S.; Sile, S.; Smith, T. J.; Kahaly, G. J.

Introduction: Teprotumumab, an IGF-IR inhibitory antibody, improves proptosis, diplopia, inflammatory signs/symptoms, and quality of life in TED. In the phase 3, double-masked, randomized, placebo-controlled trial (OPTIC), 83% receiving teprotumumab were responders (≥2 mm proptosis reduction) after 24-weeks (vs 10% placebo). Extension of OPTIC (OPTIC-X) examined retreatment benefit (additional 24-weeks) in those with: disease exacerbation (flare) or initial nonresponse and longer-term TED course. Methods: Teprotumumab/placebo OPTIC nonresponders (n = 36 placebo, n = 5 teprotumumab) at Week-24 of OPTIC (<2 mm proptosis reduction) enrolled in OPTIC-X as did flared (n = 1 placebo, n = 9 teprotumumab) (≥2 mm proptosis or ≥2 CAS increase from week-24 with absolute CAS ≥4 and symptom development) during OPTIC follow-up. Primary efficacy endpoint was proptosis responder rate. Results: In OPTIC-X, 14 teprotumumab patients were retreated and 37 placebo patients (mean TED duration of 12.3 vs 6.2 mo in OPTIC teprotumumab) received first treatment with teprotumumab. 89% of previous placebo patients were responders (mean, −3.5 mm), comparable to OPTIC results. In those retreated, 2/5 OPTIC nonresponders (proptosis reduction averaged 1.5 mm from OPTIC-X baseline, 2.5 mm from OPTIC baseline) and in 5/8 patients who flared during follow-up (proptosis reduction averaged 1.9 mm from OPTIC-X baseline, 3.3 mm from OPTIC baseline). 1 additional flare patient (5 mm proptosis reduction) had a delayed visit due to COVID and was excluded from Week-24 analysis. No new safety signals were identified. Conclusion/relevance: Teprotumumab exhibits comparable efficacy in longer duration disease to that of shorter duration. Patients who have an initial insufficient response or flare after response may safely benefit from additional teprotumumab therapy.