Ulipristal acetate compared with leuprorelin acetate for Japanese women with symptomatic uterine fibroids: a phase III randomized controlled trial

Abstract

Objective: To evaluate the efficacy and safety of ulipristal acetate (UPA) for uterine fibroids (UFs), a phase III study was conducted with leuprorelin (LEU) as a comparator. This is the first confirmatory trial of UPA for UFs among Asians. Design: Multicenter, randomized, double-blind, double-dummy, parallel-group study. Setting: Thirty-two sites in Japan. Patient(s): Patients were assigned to 2 arms, with 82 patients in the UPA group and 79 patients in the LEU group. Intervention(s): In the UPA group, 10 mg of UPA was orally administered once a day for 12 weeks. In the LEU group, 1.88 mg or 3.75 mg of LEU was subcutaneously administered at weeks 0, 4, and 8. Main Outcome Measure(s): The primary endpoint was the percentage of patients with amenorrhea for 35 days. For safety evaluation, adverse events (AEs) were recorded. Result(s): The percentage of patients with amenorrhea for 35 days was 87.0% in the UPA group and 81.8% in the LEU group, and the efficacy of UPA for causing amenorrhea for 35 days was confirmed to be noninferior to that of LEU. AEs occurred in 78.0% of the patients in the UPA group and 88.8% of the patients in the LEU group. Conclusion(s): The effect of UPA on heavy menstrual bleeding was shown to be comparable with that of LEU in Japanese patients with symptomatic UFs. No notable AEs occurred because of the UPA treatment, and the incidence of AEs in the UPA group was comparable with that of AEs in the LEU group. This result demonstrates the clinical utility of UPA for Asians.

Phase III long‐term study to evaluate the efficacy and safety of ulipristal acetate in Japanese patients with uterine fibroids

“…The rates of patients with amenorrhea for 35 days (92%-97%) and uterine bleeding normalization (99%-100%) in this study were similar to the rates for the 10-mg dose in the long-term European PEARL study (35-day amenorrhea: 80%-90%, uterine bleeding normalization: 89%-94%), 13 the 12-week Japanese dosefinding study (35-day amenorrhea: 88%, uterine bleeding normalization: 96%), 17 and the 12-week Japanese randomized trial (35-day amenorrhea: 87%, uterine bleeding normalization: 95%). 18 However, compared with the long-term PEARL study (50%-72% reduction), a lower percentage change in fibroid volume was reported in the current study (20%-35% reduction). Although no formal assessment of fibroid volume and UPA response between European and Japanese women has been conducted, it is possible that racial differences may have contributed to the differences in the reduction in fibroid volume between these studies.…”

“…In the leuprorelin comparative study in Japanese women, incidences of hot flush were lower in the UPA group than in the leuprorelin group. 18 In January 2021, the EMA recommended restricting the use of 5-mg UPA because of rare events of severe liver injury that have been reported women who had used 5-mg UPA. 16 In the current study, eight women experienced hepatic treatmentemergent AEs that were considered related to UPA.…”

A Prediction of NPVR ≥ 80% of Ultrasound-Guided High-Intensity Focused Ultrasound Ablation for Uterine Fibroids

“…/L, 350 × 10 9 /L, 400 × 10 9 /L, 450 × 10 9 /L, 500 × 10 9 /L, and 550 × 10 9 /L was 53 4,. 56.7, 60.0, 63.2, 66.3, 69.2, 72.0, 74.6, 77.1, 79.4, and 80.1%, respectively (Figure…”

“…Up to 25% of women and up to 30-40% of women older than 40 years have clinical symptoms of uterine fibroids (1)(2)(3). Many patients show clinical symptoms such as menorrhagia, irregular bleeding, pelvic pain, or infertility (4)(5)(6), which have a significant negative effect on their quality of life. Currently, the management for uterine fibroids includes surgery, medicine, uterine artery embolization (UAE), radiofrequency ablation (RFA), ultrasound-guided high-intensity focused ultrasound (USgHIFU), and magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) (7)(8)(9)(10)(11).…”

Medical treatment with ulipristal acetate for uterine fibroids: Will it be resurrected?

“…In addition, these trials demonstrated dose-response differences between the 5-and 10-mg treatment groups. This issue of racial differences in response to ulipristal acetate is further explored by Osuga et al (4) in an Asian population in this issue of Fertility and Sterility.…”