Clinical utility of ulipristal acetate for the treatment of uterine fibroids: current evidence

Figures & data

Table 1 Design of randomized trials evaluating UPA in the treatment of patients with symptomatic fibroids

Study characteristics	PEARL I	PEARL II	PEARL III	PEARL IV
Inclusion criteria	Women 18–50 years old, eligible for surgery PBAC >100 during days 1–8 of menstruation Fibroid-related anemia (<10.2 g/dL) Myomatous uterus size >16 weeks of gestation At least one fibroid of 3–10 cm BMI of 18–40	Women 18–50 years old, eligible for surgery PBAC >100 during days 1–8 of menstruation Myomatous uterus size >16 weeks of gestation At least one fibroid of 3–10 cm BMI of 18–40	Women 18–48 years old, eligible for surgery PBAC >100 during days 1–8 of menstruation Myomatous uterus size >16 weeks of gestation At least one fibroid of 3–10 cm BMI of 18–40 Regular menstrual cycles of 22–35 days with FSH <20 UI	Women 18–50 years old PBAC >100 during days 1–8 of menstruation Myomatous uterus size >16 weeks of gestation At least one fibroid of 3–10 cm BMI of 18–40 Regular menstrual cycles of 22–35 days with FSH <20 UI/L
Treatment and dosage	UPA 5 mg/day; UPA 10 mg/day; placebo	UPA 5 mg/day; UPA 10 mg/day; LA 3.75 mg/month	UPA 10 mg/day	UPA 5 mg/day; 10 mg/day
Duration of study	12 weeks	12 weeks	12 weeks Extension study: three further 3-month long courses (each course separated by two menstrual cycles)	Two 12-week long courses separated by a drug-free interval
Comparison groups	UPA 5 mg/day: 96 patients UPA 10 mg/day: 98 patients Placebo: 48 patients	UPA 5 mg/day: 97 patients UPA 10 mg/day: 103 patients LA: 101 patients	Study: 209 patients Extension study: 132 patients (107 women with four courses UPA)	UPA 5 mg/day: 228 patients UPA 10 mg/day: 223 patients
Primary objective	Efficacy of UPA: Controlling bleeding: PBAC <75 Reduction of fibroid volume at week 13	UPA is not inferior to LA in reducing the uterine bleeding	Amenorrhea at the end of each UPA course	Amenorrhea at the end of both UPA courses
Secondary objectives	Bleeding pattern Amenorrhea Hemoglobin, hematocrit, and ferritin values Pain Quality of life Tolerability of UPA	Bleeding pattern Amenorrhea Hemoglobin, hematocrit, and ferritin values Pain Quality of life Tolerability of UPA	Reduction of the three largest fibroids Pain Quality of life	Amenorrhea at the end of each UPA course Time to amenorrhea Reduction of the three largest fibroids Pain Quality of life

Abbreviations: BMI, body mass index; FSH, follicle-stimulating hormone; LA, leuprolide acetate; UPA, ulipristal acetate; PBAC, Pictorial Blood Assessment Chart.

Table 2 Outcomes of randomized trials evaluating UPA in the treatment of patients with symptomatic fibroids

Treatment	PEARL I			PEARL II			PEARL III				PEARL IV
	UPA 5 mg/day	UPA 10 mg/day	Placebo	UPA 5 mg/day	UPA 10 mg/day	LA	UPA 10 mg/day, course 1	UPA 10 mg/day, course 2	UPA 10 mg/day, course 3	UPA 10 mg/day, course 4	UPA 5 mg/day, two courses	UPA 10 mg/day, two courses
PBAC <75 at 13 weeks	91% (P<0.001)	92% (P<0.001)	19%	90%	98%	89%	NR	NR	NR	NR	81%	>86%
Amenorrhea at13 weeks	73% (P<0.001)	82% (P<0.001)	6%	75%	89%	80%	79%	89%	88%	90%	62%	73%
Days to amenorrhea	NR	NR	NR	7	5	21	4	2	3	3	5	4
Reduction in fibroid volume at 13 weeks	−21% (P=0.002)	−21% (P=0.006)	+3%	−36%	−42%	−53%	−45%	−63%	−67%	−72%	−54%	−58%

Abbreviations: LA, leuprolide acetate; NR, not reported; PBAC, pictorial bleeding assessment chart; UPA, ulipristal acetate.

Table 3 Side effects recorded in randomized trials evaluating UPA in the treatment of patients with symptomatic fibroids

Treatment	PEARL I			PEARL II			PEARL III				PEARL IV
	UPA 5 mg/day	UPA 10 mg/day	Placebo	UPA 5 mg/day	UPA 10 mg/day	LA	UPA 10 mg/day course 1	UPA 10 mg/day course 2	UPA 10 mg/day course 3	UPA 10 mg/day course 4	UPA 5 mg/day course 1	UPA 5 mg/day course 2	UPA 10 mg/day course 1	UPA 10 mg/day course 2
Serious side effects	2%	2%	6%	2%	1%	2%	0%	2%	2%	3%
Uterine hemorrhage	1%	2%	2%	0%	0%	1%		2%	0%	2%	0%	0%	0%	<1%
Fibroid protruding through cervix	0%	0%	2%	0%	1%	0%		NR	NR	NR	0%	1%	0%	0%
Breast cancer	0%	0%	2%	NR	NR	NR		NR	NR	NR	0%	0%	0%	<1%
Endometrial cancer	0%	0%	0%	NR	NR	NR		NR	NR	NR	0%	0%	<1%	0%
Headache	0%	0%	0%	1%	0%	0%		NR	NR	NR				NR
Thyroid cancer	NR	NR	NR	1%	0%	0%		0%	1%	0%				NR
Coronary arteriospasm	NR	NR	NR	NR	NR	NR		NR	NR	NR	0%	1%	0%	0%
Other side effects	46%	49%	53%	77%	77%	84%	55%	20%	29%	35%
Hot flash	NR	NR	NR	26%	24%	65%	5%	1%	4%	1%	6%	7%	4%	3%
Headache	4%	10%	4%	26%	18%	29%	14%	3%	5%	7%	9%	10%	6%	2%
Abdominal pain	2%	3%	4%	6%	11%	14%	5%	2%	1%	2%				NR
Breast pain	2%	6%	0%	5%	3%	2%	3%	0%	1%	1%	3%	2%	1%	0%
Constipation	4%	0%	2%	NR	NR	NR	NR	NR	NR	NR	0%	<1%	0%	0%
Nausea	NR	NR	NR	6%	7%	6%	3%	1%	1%	1%	3%	2%	0%	0%
Fatigue	NR	NR	NR	4%	7%	3%	3%	0%	2%	3%	1%	3%	1%	1%
Dysmenorrhea	0%	0%	4%	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR

Abbreviations: LA, leuprolide acetate; NR, not reported; UPA, ulipristal acetate.