美国托马斯杰斐逊大学William D. Schlaff研究团队在研究中取得进展。他们探索了Elagolix治疗子宫肌瘤女性月经大出血的疗效。这一研究成果2020年1月23日发表在国际顶尖学术期刊《新英格兰医学杂志》上。
Title: Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids
Author: William D. Schlaff, M.D.,, Ronald T. Ackerman, M.D.,, Ayman Al-Hendy, M.D., Ph.D.,, David F. Archer, M.D.,, Kurt T. Barnhart, M.D.,, Linda D. Bradley, M.D.,, Bruce R. Carr, M.D.,, Eve C. Feinberg, M.D.,, Sandra M. Hurtado, M.D.,, JinHee Kim, M.D.,, Ran Liu, Ph.D.,, R. Garn Mabey, Jr., M.D.,, Charlotte D. Owens, M.D.,, Alfred Poindexter, M.D.,, Elizabeth E. Puscheck, M.D., M.B.A.,, Henry Rodriguez-Ginorio, M.D.,, James A. Simon, M.D.,, Ahmed M. Soliman, Ph.D.,, Elizabeth A. Stewart, M.D.,, Nelson B. Watts, M.D.,, and Ozgul Muneyyirci-Delale, M.D.
Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding.
We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal “add-back” therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation.
A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy.
Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.)