Teprotumumab Efficacy, Safety, and Durability in Longer-Duration Thyroid Eye Disease and Re-treatment

被引:86
|
作者
Douglas, Raymond S. [1 ]
Kahaly, George J. [2 ]
Ugradar, Shoaib [3 ]
Elflein, Heike [4 ]
Ponto, Katharina A. [4 ,5 ]
Fowler, Brian T. [6 ]
Dailey, Roger [7 ]
Harris, Gerald J. [8 ]
Schiffman, Jade [9 ]
Tang, Rosa [9 ]
Wester, Sara [10 ]
Jain, Amy Patel [1 ]
Marcocci, Claudio [11 ]
Marino, Michele [11 ]
Antonelli, Alessandro [12 ]
Eckstein, Anja [13 ]
Fuhrer-Sakel, Dagmar [14 ]
Salvi, Mario [15 ]
Sile, Saba [16 ]
Francis-Sedlak, Megan [16 ]
Holt, Robert J. [16 ]
Smith, Terry J. [17 ,18 ]
机构
[1] Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA
[2] Johannes Gutenberg Univ JGU, Med Ctr, Dept Med 1, Mainz, Germany
[3] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA
[4] Johannes Gutenberg Univ Mainz, Med Ctr, Dept Ophthalmol, Mainz, Germany
[5] Johannes Gutenberg Univ Mainz, Med Ctr, Ctr Thrombosis & Hemostasis, Mainz, Germany
[6] Univ Tennessee, Hlth Sci Ctr, Memphis, TN 38163 USA
[7] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA
[8] Med Coll Wisconsin, Eye Inst, Milwaukee, WI 53226 USA
[9] Neuroeye Clin Trials Inc, Eye Wellness Ctr, Houston, TX USA
[10] Univ Miami, Bascom Palmer Eye Inst, Miami, FL USA
[11] Univ Hosp Pisa, Endocrine Unit 2, Dept Clin & Expt Med, Pisa, Italy
[12] Univ Pisa, Dept Surg Med & Mol Pathol & Crit Care, Pisa, Italy
[13] Univ Duisburg Essen, Univ Hosp Essen, EUGOGO Ctr Essen, Dept Ophthalmol, Essen, Germany
[14] Univ Duisburg Essen, Univ Hosp Essen, EUGOGO Ctr Essen, Dept Endocrinol Diabet & Metab, Essen, Germany
[15] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Endocrinol, Milan, Italy
[16] Horizon Therapeut Plc, Deerfield, IL USA
[17] Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI USA
[18] Univ Michigan, Sch Med, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI USA
基金
美国国家卫生研究院;
关键词
Long-term; Proptosis; Re-treatment; Teprotumumab; Thyroid eye disease; QUALITY-OF-LIFE; GRAVES OPHTHALMOPATHY; RECEPTOR; FIBROCYTES; ORBITOPATHY; TSH;
D O I
10.1016/j.ophtha.2021.10.017
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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 retreatment. 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. (C) 2021 by the American Academy of Ophthalmology.
引用
收藏
页码:438 / 449
页数:12
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