Ulipristal Acetate for Treatment of Uterine Leiomyomas

Abstract

OBJECTIVE: To assess the efficacy and tolerability of ulipristal acetate, a selective progesterone receptor modulator, for treatment of symptomatic uterine leiomyomas. METHODS: This phase 3, double-blind, double-dummy, placebo-controlled trial randomized premenopausal women (18–50 years) with uterine leiomyomas and abnormal uterine bleeding to once-daily 5 mg ulipristal, 10 mg ulipristal, or placebo in two 12-week treatment courses separated by a drug-free interval of two menses. Coprimary end points were rates of and time to amenorrhea during course 1. Change from baseline to end of course 1 in the Revised Activities subscale of the Uterine Fibroid Symptom and Health-Related Quality of Life questionnaire was a secondary end point. A sample size of 400 was planned to compare separately each ulipristal dose with placebo. RESULTS: From January 2014 through November 2016, 432 women were randomized. Demographic characteristics were similar across treatment groups. In course 1, 68 of 162 (42.0% [97.5% CI 33.3–51.1]) and 86 of 157 (54.8% [97.5% CI 45.5–63.8]) patients treated with 5 mg and 10 mg ulipristal, respectively, compared with 0 of 113 (0.0% [97.5% CI 0.0–3.8]) patients treated with placebo achieved amenorrhea (P<.001 for each dose); most women who achieved amenorrhea did so within 10 days (time to amenorrhea, P<.001 for each dose). Significantly greater improvements in Uterine Fibroid Symptom and Health-Related Quality of Life Revised Activities subscale scores were reported with 5 mg and 10 mg ulipristal compared with placebo (least squares mean change from baseline: 48.3, 56.7, and 13.0, respectively; P<.001 for each dose). Both ulipristal doses were well tolerated; in course 1, hot flush occurred in 7.5%, 11.6%, and 1.7% of patients treated with 5 mg ulipristal, 10 mg ulipristal, and placebo, respectively. CONCLUSION: Treatment with 5 mg or 10 mg ulipristal was superior to placebo in achieving amenorrhea and generally well tolerated for the medical management of symptomatic uterine leiomyomas. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02147158.

A systematic review and meta‐analysis of ulipristal acetate for symptomatic uterine fibroids

“…All studies were RCTs. Four studies were multicenter trials: two from European centers and two from North American centers . Two single‐site studies were conducted in the USA …”

“…All studies included women of reproductive age (ranging from 18 to 50 years), who had symptomatic fibroids (menorrhagia, pelvic pressure). Three studies diagnosed uterine fibroids by ultrasonography, and three by MRI . The ethnic groups of the participants included white, black, Asian, and Hispanic.…”

“…One study compared oral UPA 5 and 10 mg daily versus leuprolide acetate 3.75 mg monthly. Five studies compared UPA versus placebo . Three studies compared UPA 5 and 10 mg versus placebo and two studies compared UPA 10 and 20 mg versus placebo.…”

“…Five studies compared UPA with placebo . Amenorrhea was reported in five trials (882 participants): RR 24.54 (95% CI, 10.82–55.64) (Fig.…”

“…An ideal pharmacological intervention for symptomatic fibroids would reduce fibroid size and improve menorrhagia, anemia, and quality of life without adversely affecting fertility or causing adverse events. New evidence has emerged from recent large randomized controlled trials (RCTs) and new pharmacovigilance review of safety . This highlights the need for an updated systematic review assessing the benefits and harms of UPA to treat women with uterine fibroids, adhering to the PRISMA statement, comprehensively searching all relevant databases, properly assessing risk of bias in individual trials, and properly developing a GRADE evidence profile.…”