Table II.

PEARL trial characteristics with patient baseline characteristics and outcomes.

	PEARL I: Ulipristal vs placebo for 3 months (Donnez et al., 2012a)			PEARL II: Ulipristal vs GnRHa* for 3 months (Donnez et al., 2012b)			PEARL III-Extensions: Ulipristal 10 mg 4 repeated courses (Donnez et al., 2014)			PEARL III-2nd Extension: Ulipristal 10 mg 8 repeated courses (Fauser et al., 2017)	PEARL IV: Ulipristal 5 vs 10 mg 2 repeated courses (Donnez et al., 2015)			PEARL IV-Extension: Ulipristal 5 vs 10 mg 4 repeated courses (Donnez et al., 2016)
Design	Randomized, parallel-group, double-blind, placebo-controlled			Randomized, parallel-group, double-blind, double-dummy, active-comparator–controlled			Repeated intermittent ulipristal courses, followed by randomized double-blind NETA† or placebo			Optional, long-term, open-label extension, available to PEARL III first extension participants	Randomized, double-blind controlled trial			Randomized, double- blind controlled trial
Patients	85% Caucasian			85% Caucasian			86% Caucasian			94% Caucasian	5 mg ulipristal: 93% Caucasian 10 mg ulipristal: 96% Caucasian			5 mg ulipristal: 93% Caucasian 10 mg ulipristal: 96% Caucasian
Baseline fibroid characteristics:	Total fibroids:			3 Largest fibroids:			3 Largest fibroids:			BL fibroid characteristics: not mentioned in publication	BL fibroid characteristics for PEARL IV and its extension are the same, as this is the same BL population
	5 mg ulipristal			5 mg ulipristal		GnRHa	1 Course		4 Courses		3 Largest fibroids:	5 mg	10 mg
Volume (cm3)	100.7			79.6		59.2	53.9		49.8			42.6	43.6
Diameter (cm)	∼5.8			∼5.3		∼4.8	∼4.7		∼4.6			∼4.3	∼4.4
Complaints based on Questionnaires‡	Mild:		Severe:	Mild:		Severe:	Mild:		Severe:		Mild:				Severe:
	SF MGPQ  6.5 VAS 49.0 Discomfort 14.0		PBAC >200	SF MGPQ  9.0 VAS 49.0 SSS 54.0 HRQOL 53.0		PBAC >200	SF MGPQ  8.0 VAS 38.0 SSS 47.7 HRQOL 57.1		PBAC >200		–	–	–		PBAC > 200
											VAS	39.5	43.0
											SSS	50.0	50.0
											HRQOL	56.9	55.2
Intervention	Ulipristal 5 mg: 96 patients Ulipristal 10 mg: 98 patients			Ulipristal 5 mg: 97 Ulipristal 10 mg: 103			Ulipristal 10 mg + 10 days NETA 10 mg			Ulipristal 10 mg	Ulipristal 5 mg: 228 patients
Comparison	Placebo: 48 patients			GnRHa: 101 patients			Ulipristal 10 mg + 10 days placebo			–	Ulipristal 10 mg: 223 patients
Outcomes	Ulipristal showed a significant effect compared to placebo in terms of: Reduction of bleeding Amenorrhoea rates Reduction in fibroid volume Adverse events (AE) monitored (PAECs•) for up to 6 months after stopping treatment Surgical parameters were not evaluated			Ulipristal was not inferior to GnRHa in terms of bleeding reduction Bleeding control was obtained more rapidly with ulipristal GnRHa showed a more marked reduction of fibroid volume; more regrowth (>6 months) was observed, when compared with ulipristal GnRHa showed more hot flushes Endometrial-biopsies showed reversible PAECs Surgical parameters were not evaluated			±60% (N = 132) started 2 courses ±50% (N = 107) started 4 courses Amenorrhoea rates were stable (±89%) over repeated courses All endometrial biopsies showed benign histology without hyperplasia NETA did not affect fibroid volume or endometrial histology Fibroid volume reduction increased slightly with repeated courses, after course 4: 82% had >25% reduction 69.8% had >50% reduction			N = 54 started all 8 courses PAEC remained stable and benign over repeated courses (±20%) AE were stable (9–19%) over repeated courses Most frequent AE were headache and hot flush Laboratory parameters¶ (including Hb, AST, ALT and TB) remained stable and within normal ranges over repeated courses	Amenorrhoea rates were comparable over both treatment courses and both groups Controlled bleeding in between two treatment courses was >80% After treatment course 2, median fibroid reduction was 54% vs 58% for the 5 and 10 mg groups, respectively 5% drop-out due to AE Laboratory parameters (incl. Hb, AST, ALT and TB) remained stable and within normal ranges over repeated courses			Fibroid volume reduction increased slightly with repeated courses After course 4: 82% (5 mg) vs 88% (10 mg) had >25% reduction 67% (5 mg) vs 73% (10 mg) had >50% reduction Stable outcomes in both treatment groups and over repeated courses regarding: Amenorrhoea rates Laboratory parameters PAEC (stayed benign and reversible)

^* GnRHa: GnRH agonist.

^† NETA: norethisterone acetate.

^‡ Questionnaires: SF-MGPQ: Short-Form McGill Pain Questionnaire (range 0–45 points, with higher scores indicating more severe pain); VAS: Visual Analogue Scale (range 0–100 points, with higher scores indicating more severe pain); Discomfort: measurement of discomfort questionnaire (range 0–28 points, with higher scores indicating greater discomfort); PBAC: pictorial blood-loss assessment chart. Higher scores indicate more blood loss with cut-off for HMB was set on 100 points in the PEARL trials. SSS: Symptom Severity Score (range 0–100, higher scores indicating increased severity); HRQOL: health-related quality of life score (range 0–100, higher scores indicating a better quality of life).

^• PAEC: PRM-Associated-Endometrial Changes.

^¶ Laboratory parameters: Hb: haemoglobin; ALT: alanine aminotransferase; AST: aspartate aminotransferase; TB: total bilirubin.