Long-term treatment of uterine fibroids with Ulipristal Acetate44
Jacques Donnez, M.D., Francisco Vázquez, M.D., Janusz Tomaszewski, M.D., Kazem Nouri, M.D., Philippe Bouchard, M.D., Bart C. J. M. Fauser, M.D., David H. Barlow, F.R.C.O.G., Santiago Palacios, M.D., Olivier Donnez, M.D., Elke Bestel, M.D., Ian Osterloh, M.R.C.P., and Ernest Loumaye, M.D., PEARL III and the PEARL III extension study;
Fert and Sterility 2014;101:1565-1573
To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.
Design of PEARL III study + extension
PEARL III and its extension were long-term Phase III, multicentre, open-label trials of UPA, open labelled and placebo-controlled toward the administration of progestin after each ulipristal acetate treatment course.
- Uterine bleeding control was sustained in the majority (80-90%) of women treated with repeated courses.
- ~80% achieved amenorrhoea during 1st treatment course, increasing to ~90% with repeated treatment courses†.
- Amenorrhoea was achieved after a median of 4, 2, 3 and 3 days respectively for treatment courses 1, 2 , 3 and 4.
- Pain levels were reduced and maintained at the lower leverls during all treatment courses.
- Quality of life scores indicated substantially reduced QoL at baseline, but mean scores were within the range of healthy participants at the end of each treatment course and the improvement was largely maintained at the 3-month follow-up after the final treatment course ‡§.
- Median reduction from baseline in fibroid volume of the 3 largest fibroids was -45%, -63%, -67% and -72% for treatment courses 1, 2, 3 and 4 respectively.
Safety and tolerability
- The majority of adverse events were mild or moderate in nature and did not increase with successive treatment courses.
- Headache and nasopharyngitis were the most common adverse events reported during the study, but the incidences decreased after each treatment course.
- Severe AEs occurred in only 3.8% of women during the 1st course of treatment. Only one (Treatment Emergent Adverse Event) TEAE led to treatment withdrawal.
- Transient increases in endometrial thickness occurred in < 19% of woman after each treatment course.
- No cases of endometrial hyperplasia or adenocarcinoma were reported at any timepoint for any woman.
- All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology.
† Amenorrhoea defined as no bleeding for a continuous period of ≥35 days (1 day of spotting allowed).
‡ Quality of Life was measured by general EQ-5D questionnaire and the Uterine fibroid symptom and health-related quality of life (UFS-QoL) questionnaire.
§ Pain was measured with the short-form McGill pain questionnaire.