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relugolix联合疗法治疗子宫肌瘤症状
Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy


Ayman Al-Hendy ... 肿瘤 妇产科和儿科 • 2021.02.18
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症状性子宫肌瘤药物治疗新方法——口服GnRH拮抗剂

 

朱兰*,戴毓欣

北京协和医院妇产科;国家妇产疾病临床研究中心

*通讯作者

 

以月经过多、压迫症状等为表现的症状性子宫肌瘤,因极少恶变且患者多为有保留生育需求的育龄期女性,所以微无创治疗尤其是药物治疗是目前治疗领域的热点。鉴于子宫肌瘤为雌激素依赖性的良性子宫肿瘤,迅速、可逆地抑制卵巢雌激素是有效改善肌瘤相关贫血和压迫症状的关键。以往相关的临床药物应用和研发主要集中在促性腺激素释放激素激动剂(gonadotropin-releasing hormone agonists,GnRH)和选择性孕激素受体调节剂。

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摘要


背景

子宫肌瘤是引起月经量多和疼痛的常见原因。relugolix(口服促性腺激素释放激素受体拮抗剂)、雌二醇和醋酸炔诺酮每日一次给药联合治疗可能对子宫肌瘤合并月经量多的患者有效,同时可避免低雌激素效应。

 

方法

我们在子宫肌瘤合并月经量多的患者中开展了两项相同设计的国际性、双盲、24周、3期试验。我们以1∶1∶1的比例将参与者随机分组,三组分别接受每日一次安慰剂、relugolix联合疗法(40 mg relugolix、1 mg雌二醇和0.5 mg醋酸炔诺酮)或延迟relugolix联合疗法(40 mg relugolix单药治疗,之后接受relugolix联合治疗,每种治疗持续12周)治疗。两项试验的主要疗效终点均为与安慰剂组相比,relugolix联合治疗组达到缓解(月经血量<80 mL并且相对于基线减少≥50%)的参与者百分比。关键次要终点包括闭经、月经血量、因出血和盆腔不适而痛苦、贫血、疼痛、肌瘤体积和子宫体积。本试验还评估了安全性和骨密度。

 

结果

试验L1的388名女性和试验L2的382名女性接受了随机分组。在试验L1和试验L2的relugolix联合治疗组中,分别有73%和71%的参与者达到缓解(主要终点),而安慰剂组的这一比例分别为19%和15%(两项比较的P<0.001)。对于7项关键次要终点中的6项(包括月经血量[包括闭经]、疼痛、因出血和盆腔不适而痛苦、贫血和子宫体积),两个relugolix联合治疗组与安慰剂组相比均有显著改善,但在肌瘤体积方面无显著改善。relugolix联合治疗组和安慰剂组的不良事件发生率相似。relugolix联合治疗组和安慰剂组的骨密度相似,但relugolix单药治疗后骨密度降低。

 

结论

在子宫肌瘤患者中,与安慰剂相比,每日给药一次的relugolix联合治疗显著减少了月经血量,并且维持了骨密度(由Myovant Sciences资助;LIBERTY 1[L1]和LIBERTY 2[L2]在ClinicalTrials.gov注册号分别为NCT03049735和NCT03103087)。





作者信息

Ayman Al-Hendy, M.D., Ph.D., Andrea S. Lukes, M.D., Alfred N. Poindexter, III, M.D., Roberta Venturella, M.D., Ph.D., Claudio Villarroel, M.D., Hilary O.D. Critchley, M.D., Yulan Li, Ph.D., Laura McKain, M.D., Juan C. Arjona Ferreira, M.D., Andria G.M. Langenberg, M.D., Rachel B. Wagman, M.D., and Elizabeth A. Stewart, M.D.
From the Department of Obstetrics and Gynecology, University of Chicago, Chicago (A.A.-H.); Carolina Women’s Research and Wellness Center, Durham, NC (A.S.L.); Advances in Health, Houston (A.N.P.); the Department of Clinical and Experimental Medicine, Unit of Obstetrics and Gynecology, Magna Graecia University of Catanzaro, Catanzaro, Italy (R.V.); the Institute for Mother and Child Research, Faculty of Medicine, University of Chile, Santiago, Chile (C.V.); the Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom (H.O.D.C.); Myovant Sciences, Brisbane, CA (Y.L., L.M., J.C.A.F., A.G.M.L., R.B.W.); and the Department of Obstetrics and Gynecology, Mayo Clinic and Mayo Clinic Alix School of Medicine, Rochester, MN (E.A.S). Address reprint requests to Dr. Al-Hendy at the Department of Obstetrics and Gynecology, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, or at aalhendy@bsd.uchicago.edu.

 

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