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Elagolix可有效治疗子宫肌瘤患者月经大出血
作者:小柯机器人 发布时间:2020/1/31 15:35:14

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。

子宫肌瘤是激素反应性肿瘤,与月经大出血有关。Elagolix是一种口服的促性腺激素释放激素拮抗剂,可快速、可逆地抑制卵巢性激素,并减少子宫肌瘤相关出血。

研究组进行了两个相同、双盲、随机、安慰剂对照、为期6个月的临床3期试验(UF-1和UF-2),以评估Elagolix每次300mg,每日两次联合激素“反加”疗法治疗女性肌瘤相关出血的疗效。试验还包括一个单独的Elagolix组,以评估反加疗法对Elagolix雌激素作用的影响。主要终点定义为在最后一个月内月经失血量小于80毫升,且从基线到最后一个月月经失血量至少减少50%。

UF-1共招募了412名女性,UF-2共招募了378名女性,随机接受Elagolix或安慰剂治疗。UF-1接受Elagolix联合反加治疗的206名女性中有68.5%达到主要终点,接受安慰剂治疗的102名女性中有8.7%;UF-2接受Elagolix联合反加治疗的189名女性中有76.5%达到主要终点,接受安慰剂治疗的94名女性中有10%,两组内各自差异均具有统计学意义。

UF-1单独服用Elagolix的104名女性中有84.1%达到主要终点,UF-2组的95名女性中有77%。Elagolix联合反加疗法与安慰剂相比更容易发生潮红和子宫出血。反加疗法可减弱Elagolix的低雌激素作用,尤其是骨密度的降低。

总之,Elagolix联合反加疗法可有效减少子宫肌瘤患者的月经大出血。

附:英文原文

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.

Issue&Volume: 2020-01-22

Abstract:

Background

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.

Methods

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.

Results

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.

Conclusions

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.)

DOI: 10.1056/NEJMoa1904351

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1904351

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home