Relugolix Combination Therapy Improves Uterine Fibroid Symptoms Independent of Fibroid Location over 24 Weeks

Abstract

<h3>Study Objective</h3> To evaluate the impact of fibroid location (submucosal, intramural, or subserosal) on treatment outcomes with relugolix combination therapy (Relugolix-CT) in women with uterine fibroid (UF)-associated heavy menstrual bleeding (HMB) in the LIBERTY 1 (L1) and LIBERTY 2 (L2) studies. <h3>Design</h3> L1 and L2 were replicate, Phase 3, double-blind, 24-week trials. <h3>Setting</h3> 80 (L1) and 99 (L2) research centers globally. <h3>Patients or Participants</h3> Premenopausal women (age 18–50 years) with diagnosed UF (confirmed on ultrasonography) and HMB (assessed by the alkaline hematin method). <h3>Interventions</h3> Participants were randomized to once-daily Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) or placebo for 24 weeks. <h3>Measurements and Main Results</h3> Fibroid location was investigator-defined using ultrasound; FIGO type 0/1 fibroids were excluded. Menstrual blood loss (MBL) volume was measured by alkaline hematin method (responders: MBL volume <80mL and ≥50% reduction from baseline over last 35 days of treatment). Pain and other UF-associated symptoms were evaluated using the Numerical Rating Scale and Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (Symptom Severity scale) in this <i>post-hoc</i> analysis<i>.</i> Pooled L1 and L2 data were used. In the Relugolix-CT (N=253) and placebo (N=256) groups, fibroid location was categorized as subserous (N=50 and N=58), intramural (N=115 and N=130), submucosal (N=46 and N=43) or "other/unknown" (N=119 and N=106). Overall, 136 women had >1 type of fibroid and were therefore included in >1 subgroup. Baseline characteristics, including MBL volume, pain and quality of life scores, were similar between subgroups. For each fibroid subgroup, respectively, women randomized to Relugolix-CT had comparable responder rates: 76.0%, 79.1%, 80.4%, and 65.6% at Week 24, which were higher than with placebo: 24.1%, 16.2%, 14.0%, and 16.0% (all nominal p<0.0001). Across all subgroups, Relugolix-CT resulted in significant reductions in MBL volume, UF-associated pain and Symptom Severity versus placebo. <h3>Conclusion</h3> Relugolix-CT improved HMB and other UF-associated symptoms through 24 weeks independent of fibroid location.