Efficacy and safety of elagolix with add-back therapy in women with uterine fibroids and coexisting adenomyosis

Abstract

Objective: To determine if coexisting adenomyosis limits the efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy in reducing heavy menstrual bleeding in women with uterine fibroids.

Design: Pooled analysis of two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids [UF]-1 and UF-2).

Setting: A total of 153 gynecological clinical care settings in the United States and Canada.

Patients: Premenopausal women (18-51 years) with >80 mL of menstrual blood loss (MBL)/cycle and uterine fibroids with and without coexisting adenomyosis diagnosed by ultrasound and/or magnetic resonance imaging at baseline.

Interventions: Participants were randomized 1:1:2 to placebo, elagolix 300 mg twice daily alone, or elagolix 300 mg twice daily with estradiol 1 mg/norethindrone acetate 0.5 mg once daily.

Main outcome measures: The primary endpoint was the proportion of women who had <80 mL of MBL during the final month and ≥50% reduction in MBL from baseline to the final month. Adverse events were monitored.

Results: Of 786 women treated across the two trials, 16% (126 women) had coexisting adenomyosis. Among this subset, a significantly greater proportion of women who received elagolix with add-back therapy (77.1% [95% confidence interval, 66.2, 88.0]) met both primary endpoint criteria compared with women who received placebo (12.2% [95% confidence interval, 1.0, 23.4]). Adverse events most frequently reported in the elagolix with add-back adenomyosis subset were hot flushes (18.3%), nausea (11.7%), and night sweats (8.3%).

Conclusions: Elagolix with add-back therapy significantly reduced heavy menstrual bleeding in women with uterine fibroids and coexisting adenomyosis, suggesting that elagolix efficacy was not adversely affected by the presence of adenomyosis (Elaris UF-1 and UF-2 Clinical-Trials.gov numbers, NCT02654054 and NCT02691494).

Keywords: Adenomyosis; elagolix; uterine fibroids.

© 2021 The Author(s).

Figures

Figure 1

Primary endpoint: reduction in heavy menstrual bleeding. Four women who were randomized and treated before the trial registration date were excluded from this analysis. Error bars indicate 95% confidence interval. Statistical significance compared with placebo was by pooling the results from a logistic regression model including treatment and study as the main effects and baseline MBL volume as a covariate in each data set from multiple imputation. ∗P<.05, ∗∗P<.01, and ∗∗∗P<.001. Final month was defined as the last 28 days before and including the last treatment period visit date. If data on menstrual blood loss (measured using the alkaline hematin method) that could be evaluated were available between the last treatment period visit date and the last dose date, then the last dose date was used. Statistical comparisons were not made between adenomyosis subsets. LS = least squares; MBL = menstrual blood loss.