Ulipristal Acetate versus Leuprolide Acetate for Uterine Fibroids43
Jacques Donnez, M.D., Ph.D., Janusz Tomaszewski, M.D., Ph.D., Francisco Vázquez, M.D., Ph.D., Philippe Bouchard, M.D., Boguslav Lemieszczuk, M.D., Francesco Baró, M.D., Ph.D., Kazem Nouri, M.D., Luigi Selvaggi, M.D., Krzysztof Sodowski, M.D., Elke Bestel, M.D., Paul Terrill, Ph.D., Ian Osterloh, M.R.C.P., and Ernest Loumaye, M.D., Ph.D., for the PEARL II Study Group
N Engl J Med 2012; 366(5): 421-432
To demonstrate non-inferior efficacy of Ulipristal Acetate (UPA) versus Gonadotrophin Releasing Hormone (GnRH) agonist in reducing, prior to surgery, excessive uterine bleeding caused by uterine fibroids. The co-primary safety objectives were to show a superior safety and tolerance of UPA versus GnRH agonist in terms of serum oestradiol levels at end of treatment (week 13) and the proportion of patients with moderate-to-severe hot flushes during treatment.
Design of PEARL II study
A Phase III, randomised, parallel-group, double-blind, double-dummy, active comparator-controlled, multicentre study comparing UPA versus once-monthly injections of GnRH agonist leuprolide acetate 3.75mg.
- Uterine bleeding was controlled in 90% of the women receiving Esmya® 5mg. This compares with bleeding controlled in 98% of those receiving UPA 10 mg and 89% of those receiving GnRH agonist.
- Excessive bleeding was controlled significantly more rapidly in patients receiving Esmya® 5mg or UPA 10mg, than in those receiving GnRH agonist (P<0.001, both comparisons).
- Median times to amenorrhoea were 7 days for patients receiving Esmya® 5mg. This compares to 5 days for those receiving UPA 10mg, and 21 days for those receiving GnRH agonist.
- All treatments reduced the volume of the 3 largest fibroids. Median reductions at week 13 were 36%, 42% and 53% for the Esmya® 5mg, UPA 10mg and GnRH agonist groups, respectively.
- For patients who did not undergo a hysterectomy or myomectomy, UPA showed a more sustained effect on the reduction of myoma volume up to 6 months after treatment cessation compared to GnRH agonist.
Safety and tolerability
- Median oestradiol levels at week 13 were maintained at approximately 60-65 pg/mL in both the UPA groups but had decreased to post-menopausal levels (25.0 pg/mL) with GnRH agonist.
- Significantly lower incidence of moderate to severe hot flashes with Esmya® 5mg or UPA 10mg (< 11%) when compared to GnRH agonist (40%) (P<0.001 for both comparisons).
- Mean endometrial thickness at week 13 was significantly different between the UPA and GnRH agonist groups (p < 0.001 for both comparisons) with means of 9.4mm and 10.1 mm in the Esmya® 5mg and UPA 10mg respectively, compared to 5,1 mm in the GnRH agonist group.