美国洛杉矶雪松西奈山医疗中心Raymond S. Douglas课题组的一项最新研究发现Teprotumumab可治疗活动性甲状腺眼病。该项研究成果发表在2020年1月23日出版的《新英格兰医学杂志》上。
Title: Teprotumumab for the Treatment of Active Thyroid Eye Disease
Author: Raymond S. Douglas, M.D., Ph.D.,, George J. Kahaly, M.D., Ph.D.,, Amy Patel, M.D.,, Saba Sile, M.D.,, Elizabeth H.Z. Thompson, Ph.D.,, Renee Perdok, M.S.,, James C. Fleming, M.D.,, Brian T. Fowler, M.D.,, Claudio Marcocci, M.D.,, Michele Marinò, M.D.,, Alessandro Antonelli, M.D.,, Roger Dailey, M.D.,, Gerald J. Harris, M.D.,, Anja Eckstein, M.D.,, Jade Schiffman, M.D.,, Rosa Tang, M.D.,, Christine Nelson, M.D.,, Mario Salvi, M.D.,, Sara Wester, M.D.,, Jeffrey W. Sherman, M.D.,, Thomas Vescio, M.D.,, Robert J. Holt, Pharm.D.,, and Terry J. Smith, M.D.
Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration–approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease.
In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves’ ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful).
A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients  vs. 7% ), Clinical Activity Score of 0 or 1 (59%  vs. 21% ), the mean change in proptosis (?2.82 mm vs. ?0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation.
Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon.