Li, Yulan

What is this summary about? This is a summary of a research study (known as a clinical trial) called the LIBERTY extension study. The LIBERTY extension study is a long-term study looking at how well a medicine called relugolix combination therapy worked in reducing blood loss during menstrual periods in women with uterine fibroids with heavy menstrual periods. Women were included in the extension study if they finished the 24-week LIBERTY 1 or LIBERTY 2 studies. Heavy menstrual periods were considered to be menstrual blood loss of about one-third of a cup of blood (80 ml) per cycle for two cycles or about two-thirds of a cup of blood (160 ml) during one cycle. The LIBERTY extension study also looked at whether relugolix combination therapy was safe to take for up to 1 year. What were the results? Out of 770 total women with uterine fibroids with heavy menstrual bleeding who took part in the LIBERTY 1 and LIBERTY 2 studies, 476 took part in the LIBERTY extension study. From the start of the LIBERTY 1 and LIBERTY 2 studies through the end of the LIBERTY extension: 163 women took relugolix combination therapy for 52 weeks 149 women took relugolix alone for 12 weeks followed by relugolix combination therapy for 40 weeks 164 women took placebo for 24 weeks followed by relugolix combination therapy for 28 weeks The LIBERTY extension study showed that most women in all three treatment groups responded to relugolix combination therapy by having less bleeding during their menstrual periods, having improved anemia symptoms, and having stable bone mineral loss. Side effects were similar across treatment groups, and the most common side effects were headaches and hot flushes. What do the results mean? Women with uterine fibroids with heavy menstrual bleeding taking relugolix combination therapy may have fewer uterine fibroid bleeding symptoms for up to 1 year of treatment. Clinical Trial Registration: NCT03049735 ( ClinicalTrials.gov ) (LIBERTY 1) Clinical Trial Registration: NCT03103087 ( ClinicalTrials.gov ) (LIBERTY 2) Clinical Trial Registration: NCT03412890 ( ClinicalTrials.gov ) (LIBERTY extension study)

INTRODUCTION: Currently, pain (menstrual and non-menstrual), is poorly studied in women with uterine fibroids (UF). Relugolix combination therapy (Relugolix-CT; once-daily relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) significantly improved UF-associated heavy menstrual bleeding in the two LIBERTY randomized phase 3 trials. METHODS: In the LIBERTY 1 and 2 Institutional Review Board-approved studies, a key secondary endpoint was the proportion of women with no/minimal pain (maximal pain score ≤1 on the 0–10 numerical rating scale [NRS] during the last 35 days of treatment) in the pain-evaluable population (women with maximum pain NRS ≥4 during the 35 days prior to randomization). Pain was also evaluated on menstrual bleeding and on non-menstrual days during the last 35 days of treatment. Treatment comparisons were performed in both studies and the pooled dataset using the Cochran–Mantel–Haenszel test stratified by baseline menstrual blood loss volume. RESULTS: After 24 weeks of treatment, a significantly greater proportion of pain-evaluable patients in the Relugolix-CT groups (43.1% and 47.1% in LIBERTY 1 and 2, respectively) had no/minimum UF-associated pain during the last 35 days of treatment compared with placebo (10.1% and 17.1%, respectively; P<.0001). The proportions of women with no/minimum dysmenorrhea and non-menstrual pain were significantly higher with Relugolix-CT (pooled data: 65.0% and 44.6%, respectively) vs placebo (19.3% and 21.6%, respectively). CONCLUSION: Over 24 weeks, once-daily Relugolix-CT reduced UF-associated pain, with a more pronounced effect on menstrual vs non-menstrual pain. Thus, Relugolix-CT improved two common symptoms (menstrual bleeding and pain) associated with UF.