Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids

Capsule:
In a prospective randomized study, repeated 12-week courses of oral ulipristal acetate effectively control bleeding and pain, reduce fibroid volume, and restore quality of life in patients with symptomatic fibroids.

Authors:
Jacques Donnez, M.D., Robert Hudecek, M.D., Olivier Donnez, M.D., Dace Matule, M.D., Hans-Joachim Arhendt, M.D., Janos Zatik, M.D., Zaneta Kasilovskiene, M.D., Mihai Cristian Dumitrascu, M.D., Hervé Fernandez, M.D., David H. Barlow, F.R.C.O.G., Philippe Bouchard, M.D., Bart C.J.M. Fauser, M.D., Elke Bestel, M.D., Paul Terrill, Ph.D., Ian Osterloh, M.R.C.P., Ernest Loumaye, M.D.

Volume 103, Issue 2, Pages 519-527

Abstract:

Objective:
To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids.

Design:
Double-blind, randomized administration of two 12-week courses of ulipristal acetate.

Setting:
Gynecology centers.

Patient(s):
A total of 451 patients with symptomatic uterine fibroid(s) and heavy bleeding.

Intervention(s):
Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate.

Main Outcome Measure(s):
Amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), pain.

Result(s):
In the 5- and 10-mg treatment groups (62% and 73% of patients, respectively) achieved amenorrhea during both treatment courses. Proportions of patients achieving controlled bleeding during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10 mg of ulipristal acetate, respectively. Pain and QoL improved in both groups. Ulipristal acetate was well tolerated with less than 5% of patients discontinuing treatment due to adverse events.

Conclusion(s):
Repeated 12-week courses of daily oral ulipristal acetate (5 and 10 mg) effectively control bleeding and pain, reduce fibroid volume, and restore QoL in patients with symptomatic fibroids.

Clinical Trial Registration Number:
NCT01629563 (PEARL IV).

  • Shvetha Zarek

    This is a secondary analysis of the PEARL IV trial; a Phase III randomized, double blind trial, and evaluates the efficacy and safety of repeated courses of either 5 or 10 mg of UPA for treatment of symptomatic uterine leiomyoma of 451 patients. Women in the 10 mg treatment group had a higher amenorrhea rate (73% vs. 62%). Diminished menstruation resumed after each treatment. Similar reduction in fibroid volume was seen in both treatment groups (5 mg- 54% and 10 mg- 58%). UPA was well tolerated. Endometrial sampling noted benign changes related to progesterone receptor modulator use in 16-19% of the patients that were reversible. Three cases of hyperplasia were noted which is < 1%.
    As UPA is increasingly used for symptomatic leiomyoma, the safety of repeated use of UPA is essential to confim. It is important to note that the second course of treatment was commenced only after the second menses after cessation of the first treatment. The endometrial histopathology is reassuring but does confirm that UPA is associated with endometrial changes that are important for patient counseling. Thank you to the esteemed authors for providing this important data that will be essential for clinical use.

  • This article presents further evidence that UPA is a very promising option in the treatment of uterine fibroids. Can the authors comment why there appears to be a lag between the uptake and use of UPA in the US versus Europe?
    Do you predict that GnRH agonists such as leuprolide will be replaced by UPA in the pre-treatment and treatment of uterine fibroids?

    • Jacques Donnez

      Can the authors comment why there appears to be a lag between the uptake and use of UPA in the US versus Europe?
      This is due to specific requirements from FDA to conduct studies in American population, which are ongoing

      Do you predict that GnRH agonists such as leuprolide will be replaced by UPA in the pre-treatment and treatment of uterine fibroids?
      Given that UPA allows to maintain mid-follicular phase estradiol levels, its use could be suitable for longer treatment periods with less sides effects, but further long term studies are required

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