Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy

Approximately 25% of women with uterine fibroids experience symptoms, most commonly heavy menstrual bleeding (HMB) or fibroid-associated pain. Long-acting gonadotropin-releasing hormone (GnRH) agonists are effective for the medical management of uterine fibroids, but their duration of use is limited by hypoestrogenic sequelae. Relugolix is an orally active nonpeptide GnRH receptor antagonist that has been shown to effectively reduce symptoms of uterine fibroids. When administered orally in combination with estradiol and norethindrone acetate, combination therapy may have minimal hypoestrogenic adverse effects and reduce the risk of endometrial hyperplasia. This article reports the results of LIBERTY1 (L1) and LIBERTY2 (L2), 2 replicate international, double-blind, randomized, placebo-controlled, phase 3 trials assessing the efficacy and safety of once-daily relugolix combination therapy, as well as delayed relugolix combination therapy in women with fibroid-associate HMB.Women aged 18 to 50 years with a diagnosis of fibroids with HMB were enrolled in Africa, Europe, North America, and South America.Women were randomized in a 1:1:1 ratio to 24weeks of placebo, relugolix combination therapy, or delayed relugolix combination therapy. The combination therapy cohort received a 40-mg relugolix tablet and a capsule containing estradiol and norethindrone acetate once daily. The delayed relugolix combination therapy group received the 40-mg relugolix tablet and a placebo capsule for 12 weeks, then were given the full combination therapy regimen for 12 weeks. The primary comparison was the percentage of participants responding to relugolix combination therapy as compared with placebo. A response was defined as a volume of menstrual blood loss less than 80 mL and a reduction of at least 50% from the baseline volume of menstrual blood loss. Efficacy and safety analyses were conducted through a modified intention-to-treat protocol.