Health-Related Quality of Life With Ulipristal Acetate for Treatment of Uterine Leiomyomas: A Randomized Controlled Trial

Andrea S Lukes, David Soper, Amanda Harrington, Vilma Sniukiene, Yifan Mo, Patrick Gillard, Lee Shulman, Andrea S Lukes, David Soper, Amanda Harrington, Vilma Sniukiene, Yifan Mo, Patrick Gillard, Lee Shulman

Abstract

Objective: To investigate effects of ulipristal acetate on health-related quality of life (QOL) and symptom severity in women with symptomatic uterine leiomyomas and abnormal uterine bleeding.

Methods: Women were randomized to ulipristal (5 mg, 10 mg) or placebo in two phase 3, multicenter, double-blind, placebo-controlled trials (VENUS I and II). Health-related QOL and symptom severity were assessed at baseline, and over one (VENUS I and II) and two (VENUS II) 12-week treatment courses using the Uterine Fibroid Symptom Health-Related Quality of Life questionnaire. In pooled VENUS I and II data, change from baseline to the end of the first course for each Uterine Fibroid Symptom Health-Related Quality of Life scale was analyzed, including a Revised Activities subscale that measured physical and social activities. The proportion of women achieving meaningful change in the Symptom Severity (20 or more points), Health-Related QOL Total (20 or more points), and Revised Activities (30 or more points) scales was calculated. In VENUS II data, change from baseline to the end of each course in each scale was analyzed for each treatment arm.

Results: In pooled analyses, the intent-to-treat population included 589 patients (placebo, n=169; ulipristal 5 mg, n=215; ulipristal 10 mg, n=205). Significantly greater improvements from baseline in all Uterine Fibroid Symptom Health-Related Quality of Life scales were observed with both ulipristal doses compared with placebo (P<.001). A meaningful change in Revised Activities was achieved by 51 patients receiving placebo (34.9%), compared with 144 (73.5%; OR 5.0 [97.5% CI 2.9-8.6]) and 141 (80.6%; OR 7.9 [97.5% CI 4.3-14.6]) patients receiving ulipristal 5 mg, and 10 mg, respectively. In VENUS II, at end of courses 1 and 2, both ulipristal doses demonstrated significant improvements from baseline compared with placebo for all Uterine Fibroid Symptom Health-Related Quality of Life scales (P<.01). Mean Revised Activities scores showed that beneficial ulipristal effects were maintained in course 2, and improvements occurred on switching to ulipristal; results for other scales were similar.

Conclusion: Ulipristal was associated with significant improvements in health-related QOL and symptom severity compared with placebo for women with symptomatic uterine leiomyomas.

Clinical trial registration: ClinicalTrials.gov, NCT02147197 and NCT02147158.

Funding source: Allergan plc, Dublin, Ireland.

Figures

Fig. 1.. Treatment randomization in VENUS I…
Fig. 1.. Treatment randomization in VENUS I (A) and VENUS II (B) and subsequent pooling of treatment groups (C). UPA, ulipristal acetate.
Lukes. Ulipristal for Uterine Leiomyomas: Quality of Life. Obstet Gynecol 2019.
Fig. 2.. Cumulative distribution function for change…
Fig. 2.. Cumulative distribution function for change from baseline in Uterine Fibroid Symptom and Health-Related Quality of Life questionnaire (UFS-QOL) Revised Activities subscale score at end of treatment (end of treatment in VENUS I and end of treatment course 1 in VENUS II): pooled VENUS I and VENUS II. The vertical line denotes the responder threshold. A responder is defined as a patient who achieved 30 or more points of improvement in change from baseline on the Revised Activities subscale score of the UFS-QOL at end of treatment. UPA, ulipristal acetate.
Lukes. Ulipristal for Uterine Leiomyomas: Quality of Life. Obstet Gynecol 2019.
Fig. 3.. Baseline and end of treatment…
Fig. 3.. Baseline and end of treatment courses 1 and 2 Uterine Fibroid Symptom and Health-Related Quality of Life questionnaire scale scores in the treatment arms of VENUS II. Symptom Severity (A), Activities (original) (B), Revised Activities (C), Concern (D), Control (E), Energy/Mood (F), Self-Consciousness (G), Sexual Function (H), and Health-Related Quality of Life Total (I). P values are from the paired t-test comparing the mean difference between baseline and end of treatment course 1 and baseline and end of treatment course 2. P<.001 in the following treatment arms: placebo:UPA 5 mg, placebo:UPA 10 mg, UPA 5 mg:placebo, and UPA 10 mg:placebo, for all scales except control, UPA 10 mg:placebo (P=.001) and sexual function, UPA 5 mg:placebo (P=.004). P≥.05 in the following treatment arms: UPA 5 mg:UPA 5 mg and UPA 10 mg:UPA 10 mg, for all scales except Activities (original), P=.046, Revised Activities, P=.041, and Control, P=.003, in the UPA 10 mg:UPA 10 mg arm. Placebo:UPA 5 mg, n=39–40; placebo:UPA 10 mg, n=36–38; UPA 5 mg:placebo, n=38–40; UPA 10 mg:placebo, n=27; UPA 5 mg:UPA 5 mg, n=77; UPA 10 mg:UPA 10 mg, n=73–74. N indicates patients with analysis values at both baseline and postbaseline during the specified time period. Revised Activities subscale score is not included in the Health-Related Quality of Life Total score. UPA, ulipristal acetate.
Lukes. Ulipristal for Uterine Leiomyomas: Quality of Life. Obstet Gynecol 2019.
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