Teprotumumab Efficacy, Safety, and Durability in Longer-Duration Thyroid Eye Disease and Re-treatment: OPTIC-X Study

Raymond S. Douglas, George J. Kahaly, Shoaib Ugradar, Heike Elflein, Katharina A. Ponto, Brian T. Fowler, Roger Dailey, Gerald J. Harris, Jade Schiffman, Rosa Tang, Sara Wester, Amy Patel Jain, Claudio Marcocci, Michele Marinò, Alessandro Antonelli, Anja Eckstein, Dagmar Führer-Sakel, Mario Salvi, Saba Sile, Megan Francis-SedlakRobert J. Holt, Terry J. Smith

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Purpose: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. Design: The Treatment of Graves’ Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves’ Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. Participants: Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC. Methods: OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. Main Outcome Measures: Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. Results: Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, –3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment. Conclusions: Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.

Original languageEnglish (US)
Pages (from-to)438-449
Number of pages12
Issue number4
StatePublished - Apr 2022


  • Long-term
  • Proptosis
  • Re-treatment
  • Teprotumumab
  • Thyroid eye disease
  • Exophthalmos
  • Humans
  • Antibodies, Monoclonal, Humanized/therapeutic use
  • Diplopia
  • Graves Ophthalmopathy/drug therapy

ASJC Scopus subject areas

  • Ophthalmology


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