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In a phase 3 LIBERTY randomized withdrawal study spanning 2 years, relugolix combination therapy proved effective in sustaining reduced menstrual blood loss volume and alleviating symptoms in women with uterine fibroids, with a well-tolerated profile and preserved bone mineral density.

The following is a summary of “LIBERTY randomized withdrawal study: relugolix combination therapy for heavy menstrual bleeding associated with uterine fibroids,” published in the DECEMBER 2023 issue of Obstetrics and Gynecology by Al-Hendy, et al.

The LIBERTY 1 and 2 trials and the long-term extension study demonstrated the efficacy and safety of once-daily relugolix combination therapy in reducing menstrual blood loss volume and pain in women with uterine fibroids. The therapy, consisting of 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate, was well-tolerated with preserved bone mineral density over 52 weeks. For a phase 3 LIBERTY randomized withdrawal study, researchers sought to report the 2-year efficacy and safety results of relugolix combination therapy in women with uterine fibroid-associated heavy menstrual bleeding.

Women completing the 24-week LIBERTY 1 or 2 trials and the subsequent 28-week long-term extension study, meeting responder criteria, were randomized 1:1 to receive either blinded relugolix combination therapy or placebo for 52 weeks (total treatment period of 104 weeks). For those experiencing a relapse of heavy menstrual bleeding, open-label relugolix combination therapy was offered. Primary endpoints included the proportion of women maintaining menstrual blood loss volume <80 mL through week 76. Secondary endpoints comprised the time to menstrual blood loss volume ≥80 mL, the proportion of women maintaining <80 mL through week 104, the proportion achieving or maintaining amenorrhea at week 76, and changes in the Uterine Fibroid Symptom–Quality of Life Bleeding and Pelvic Discomfort Scale and symptom severity scores. Analyses were conducted for the modified intent-to-treat population.

Of 229 randomized women (relugolix combination therapy, n=115; placebo, n=114), 228 received the study drug, and 175 (76.7%) completed the randomized withdrawal study. Through week 76, 78.4% of women on relugolix combination therapy maintained menstrual blood loss volume <80 mL compared to 15.1% in the placebo group (difference, 63.4%; 95% CI, 52.9%–73.9%; P<.0001). At week 104, 69.8% of women on relugolix combination therapy maintained menstrual blood loss volume <80 mL vs 11.8% in the placebo group (difference, 58.0%; 95% CI, 47.0%–69.1%; P<.0001). Through week 104, 88.3% of women on placebo relapsed with heavy menstrual bleeding (median time to relapse, 5.9 weeks). Among the 89 women in the placebo group who relapsed and received open-label rescue treatment, 87 women responded to relugolix combination therapy with a menstrual blood loss volume <80 mL. The proportion of women achieving or maintaining amenorrhea was 57.4% vs 13.3% at week 76 (difference, 44.1%; 95% CI, 33.10%–55.1%; P<.0001) and 58.3% vs 10.6% at week 104 (difference, 47.6%; 95% CI, 37.0%–58.3%; nominal P<.0001) for relugolix combination therapy and the placebo group, respectively. Relugolix combination therapy was generally well tolerated, with no new safety signals identified. The adverse event profile over the second year remained consistent with that reported in the first year of treatment. Bone mineral density remained stable in women who received relugolix combination therapy from week 52 to week 104. In women continuously treated with relugolix combination therapy for up to 2 years, bone mineral density was generally preserved.

After 2 years, relugolix combination therapy demonstrated durable efficacy in maintaining low menstrual blood loss volume in women with symptomatic uterine fibroids. Most women experienced a return of heavy menstrual bleeding and associated symptoms after treatment cessation, which improved upon retreatment with relugolix combination therapy. The therapy was well-tolerated, and the adverse event profile remained consistent over the 2-year treatment period, with preserved bone mineral density.

Source: ajog.org/article/S0002-9378(23)00600-2/fulltext