Abstract：
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.
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.
摘要：
背景：在LIBERTY长期扩展研究中，每日一次relugolix联合治疗(40毫克relugolix，雌二醇1毫克，醋酸炔诺酮0.5mg）在整个52周治疗期间，在整个研究人群中，显着改善了子宫肌瘤相关的大量月经出血。
目的：与其他种族相比，黑人或非洲裔美国妇女通常经历更大程度的子宫肌瘤疾病和症状负担，并且传统上在临床试验中代表性不足。这项次要分析旨在评估LIBERTY长期扩展研究中黑人或非裔美国妇女子宫肌瘤亚组人群中relugolix联合治疗的疗效和安全性。
方法：患有子宫肌瘤和大量月经出血的黑人或非裔美国人绝经前妇女（年龄18-50岁）完成了24周的随机分组，安慰剂对照,双盲LIBERTY1（标识符：NCT03049735）或LIBERTY2（标识符：NCT03103087）试验有资格参加为期28周的LIBERTY长期扩展研究（标识符：NCT03412890），所有妇女每天接受一次，开放标签relugolix联合疗法。此子分析的主要终点是黑人或非裔美国人治疗反应者的比例：从关键研究基线到最后35天，月经失血量至少减少50％的女性关键研究随机治疗组。次要结果包括闭经的发生率以及症状负担和生活质量的变化。
结果：总体而言，477名女性中的241名（50.5%）参加了LIBERTY长期扩展研究，自我确定为黑人或非裔美国人。在接受连续relugolix联合治疗长达52周的黑人或非裔美国女性中，70名女性中的58名(82.9%；95%置信区间，72.0％-90.8％）符合治疗响应者减少大量月经出血（主要终点）的标准。从关键研究基线到第52周，月经失血量显着减少（最小二乘平均百分比变化：85.0％）；64.3％的女性实现闭经；在关键研究基线时，有59.1％的贫血女性实现了血红蛋白水平的显着改善（>2g/dL）；并且由于子宫肌瘤相关症状而导致的症状严重程度和痛苦减少，并且在52周内与健康相关的生活质量得到了改善。在累积的52周治疗期间，最常见的不良事件是潮热（12.9%），头痛（5.7%），高血压（5.7%）。骨密度保持52周。
结论：在参加LIBERTY长期延长研究的大多数黑人或非洲裔美国妇女中，每日一次relugolix联合治疗可改善子宫肌瘤相关的大量月经出血。在黑人或非裔美国女性中，relugolix联合治疗的安全性和有效性与先前发表的整个研究人群在52周内的结果一致。此子分析的结果将通过帮助提供者和黑人或非裔美国妇女了解relugolix联合治疗作为治疗子宫肌瘤相关症状的药理学选择的有效性和安全性，来帮助共同决策。
目的：与其他种族相比，黑人或非洲裔美国妇女通常经历更大程度的子宫肌瘤疾病和症状负担，并且传统上在临床试验中代表性不足。这项次要分析旨在评估LIBERTY长期扩展研究中黑人或非裔美国妇女子宫肌瘤亚组人群中relugolix联合治疗的疗效和安全性。
方法：患有子宫肌瘤和大量月经出血的黑人或非裔美国人绝经前妇女（年龄18-50岁）完成了24周的随机分组，安慰剂对照,双盲LIBERTY1（标识符：NCT03049735）或LIBERTY2（标识符：NCT03103087）试验有资格参加为期28周的LIBERTY长期扩展研究（标识符：NCT03412890），所有妇女每天接受一次，开放标签relugolix联合疗法。此子分析的主要终点是黑人或非裔美国人治疗反应者的比例：从关键研究基线到最后35天，月经失血量至少减少50％的女性关键研究随机治疗组。次要结果包括闭经的发生率以及症状负担和生活质量的变化。
结果：总体而言，477名女性中的241名（50.5%）参加了LIBERTY长期扩展研究，自我确定为黑人或非裔美国人。在接受连续relugolix联合治疗长达52周的黑人或非裔美国女性中，70名女性中的58名(82.9%；95%置信区间，72.0％-90.8％）符合治疗响应者减少大量月经出血（主要终点）的标准。从关键研究基线到第52周，月经失血量显着减少（最小二乘平均百分比变化：85.0％）；64.3％的女性实现闭经；在关键研究基线时，有59.1％的贫血女性实现了血红蛋白水平的显着改善（>2g/dL）；并且由于子宫肌瘤相关症状而导致的症状严重程度和痛苦减少，并且在52周内与健康相关的生活质量得到了改善。在累积的52周治疗期间，最常见的不良事件是潮热（12.9%），头痛（5.7%），高血压（5.7%）。骨密度保持52周。
结论：在参加LIBERTY长期延长研究的大多数黑人或非洲裔美国妇女中，每日一次relugolix联合治疗可改善子宫肌瘤相关的大量月经出血。在黑人或非裔美国女性中，relugolix联合治疗的安全性和有效性与先前发表的整个研究人群在52周内的结果一致。此子分析的结果将通过帮助提供者和黑人或非裔美国妇女了解relugolix联合治疗作为治疗子宫肌瘤相关症状的药理学选择的有效性和安全性，来帮助共同决策。
