Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Mayo Clinic and Mayo Clinic Alix School of Medicine, Rochester, MN.
Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL.
Am J Obstet Gynecol. 2024 Feb;230(2):237.e1-237.e11. doi: 10.1016/j.ajog.2023.10.030. Epub 2023 Oct 18.
In the LIBERTY Long-Term Extension study, once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) substantially improved uterine fibroid-associated heavy menstrual bleeding throughout the 52-week treatment period in the overall study population.
Black or African American women typically experience a greater extent of disease and symptom burden of uterine fibroids vs other racial groups and have traditionally been underrepresented in clinical trials. This secondary analysis aimed to assess the efficacy and safety of relugolix combination therapy in the subgroup population of Black or African American women with uterine fibroids in the LIBERTY Long-Term Extension study.
Black or African American premenopausal women (aged 18-50 years) with uterine fibroids and heavy menstrual bleeding who completed the 24-week randomized, placebo-controlled, double-blind LIBERTY 1 (identifier: NCT03049735) or LIBERTY 2 (identifier: NCT03103087) trials were eligible to enroll in the 28-week LIBERTY Long-Term Extension study (identifier: NCT03412890), in which all women received once-daily, open-label relugolix combination therapy. The primary endpoint of this subanalysis was the proportion of Black or African American treatment responders: women who achieved a menstrual blood loss volume of <80 mL and at least a 50% reduction in menstrual blood loss volume from the pivotal study baseline to the last 35 days of treatment by pivotal study randomized treatment group. The secondary outcomes included rates of amenorrhea and changes in symptom burden and quality of life.
Overall, 241 of 477 women (50.5%) enrolled in the LIBERTY Long-Term Extension study self-identified as Black or African American. In Black or African American women receiving continuous relugolix combination therapy for up to 52 weeks, 58 of 70 women (82.9%; 95% confidence interval, 72.0%-90.8%) met the treatment responder criteria for reduction in heavy menstrual bleeding (primary endpoint). A substantial reduction in menstrual blood loss volume from the pivotal study baseline to week 52 was demonstrated (least squares mean percentage change: 85.0%); 64.3% of women achieved amenorrhea; 59.1% of women with anemia at the pivotal study baseline achieved a substantial improvement (>2 g/dL) in hemoglobin levels; and decreased symptom severity and distress because of uterine fibroid-associated symptoms and improvements in health-related quality of life through 52 weeks were demonstrated. The most frequently reported adverse events during the cumulative 52-week treatment period were hot flush (12.9%), headache (5.7%), and hypertension (5.7%). Bone mineral density was preserved through 52 weeks.
Once-daily relugolix combination therapy improved uterine fibroid-associated heavy menstrual bleeding in most Black or African American women who participated in the LIBERTY Long-Term Extension study. The safety and efficacy profile of relugolix combination therapy in Black or African American women was consistent with previously published results from the overall study population through 52 weeks. Findings from this subanalysis will assist shared decision-making by helping providers and Black or African American women understand the efficacy and safety of relugolix combination therapy as a pharmacologic option for the management of uterine fibroid-associated symptoms.
在 LIBERTY 长期扩展研究中，每日一次的瑞戈非尼联合治疗（40mg 瑞戈非尼、雌二醇 1mg、醋酸炔诺酮 0.5mg）在整个 52 周的治疗期间显著改善了整体研究人群中子宫肌瘤相关的重度月经过多。
黑人和非裔美国女性通常经历更大程度的疾病和症状负担的子宫肌瘤与其他种族群体，并在临床试验中代表性不足。本二次分析旨在评估在 LIBERTY 长期扩展研究中子宫肌瘤黑人或非裔美国女性亚组人群中瑞戈非尼联合治疗的疗效和安全性。
完成 24 周随机、安慰剂对照、双盲 LIBERTY 1（标识符：NCT03049735）或 LIBERTY 2（标识符：NCT03103087）试验的 18-50 岁有子宫肌瘤和重度月经过多的黑人或非裔美国绝经前女性有资格参加为期 28 周的 LIBERTY 长期扩展研究（标识符：NCT03412890），所有女性均接受每日一次、开放标签的瑞戈非尼联合治疗。本次亚分析的主要终点是黑人或非裔美国治疗反应者的比例：在关键研究随机治疗组中，达到月经失血量<80ml 和月经失血量比关键研究基线至少减少 50%的女性。次要结局包括闭经率和症状负担及生活质量的变化。
在总共 477 名参加 LIBERTY 长期扩展研究的女性中，有 241 名（50.5%）自我认定为黑人和非裔美国人。在接受连续瑞戈非尼联合治疗长达 52 周的黑人或非裔美国女性中，70 名女性中有 58 名（82.9%；95%置信区间，72.0%-90.8%）达到了重度月经过多减少的治疗反应标准（主要终点）。从关键研究基线到第 52 周，月经失血量显著减少（最小二乘均数百分比变化：85.0%）；64.3%的女性闭经；59.1%在关键研究基线时有贫血的女性血红蛋白水平显著改善（>2g/dL）；通过 52 周，与子宫肌瘤相关的症状的严重程度和困扰得到了改善，与健康相关的生活质量得到了改善。在整个 52 周治疗期间最常报告的不良事件是热潮红（12.9%）、头痛（5.7%）和高血压（5.7%）。骨密度在 52 周内保持稳定。
每日一次的瑞戈非尼联合治疗改善了参加 LIBERTY 长期扩展研究的大多数黑人或非裔美国女性的子宫肌瘤相关重度月经过多。瑞戈非尼联合治疗在黑人或非裔美国女性中的安全性和疗效与总体研究人群在 52 周时的先前发表结果一致。本次亚分析的结果将有助于共同决策，帮助提供者和黑人和非裔美国女性了解瑞戈非尼联合治疗作为管理子宫肌瘤相关症状的药物选择的疗效和安全性。
