Relugolix combination therapy in Black/African American women with symptomatic uterine fibroids: LIBERTY Long-Term Extension study

Abstract

BackgroundIn the LIBERTY Long-Term Extension study, once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) significantly improved uterine fibroid-associated heavy menstrual bleeding over the 52-week treatment period in the overall study population. Objectives(s)Black/African American women typically experience greater extent of disease and symptom burden of uterine fibroids versus 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/African American women with uterine fibroids in the LIBERTY Long-Term Extension study. Study designBlack/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 (NCT03049735) or LIBERTY 2 (NCT03103087) trials were eligible to enroll in the 28-week LIBERTY Long-Term Extension (NCT03412890), in which all women received once-daily, open-label relugolix combination therapy. The primary endpoint of this subanalysis was the proportion of Black/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 pivotal study baseline to the last 35 days of treatment by pivotal study randomized treatment group. Secondary outcomes included rates of amenorrhea, as well as changes in symptom burden and quality of life. ResultsIn total, 241/477 (50.5%) women enrolled into the LIBERTY Long-Term Extension study self-identified as Black or African American. In Black/African American women receiving continuous relugolix combination therapy for up to 52 weeks, 82.9% [n=58/70; 95% confidence interval: 72.0%, 90.8%] met treatment responder criteria for reduction in heavy menstrual bleeding (primary endpoint). A substantial reduction in menstrual blood loss volume from 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 due to uterine fibroid-associated symptoms was demonstrated, as well as improvements in health-related quality of life through 52 weeks. 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. Conclusion(s)Once-daily relugolix combination therapy improved uterine fibroid-associated heavy menstrual bleeding in the majority of Black/African American women who participated in the LIBERTY Long-Term Extension. The safety and efficacy profile of relugolix combination therapy in Black/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/African American women understand the efficacy and safety of relugolix combination therapy as a pharmacologic option for the management of uterine fibroid-associated symptoms.