Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids.

Abstract

BACKGROUND:

Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding.

METHODS:

We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation.

RESULTS:

A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy.

CONCLUSIONS:

Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.).

• Authors: William D Schlaff, Ronald T Ackerman, Ayman Al-Hendy, David F Archer, Kurt T Barnhart, Linda D Bradley, Bruce R Carr, Eve C Feinberg, Sandra M Hurtado, JinHee Kim, Ran Liu, R Garn Mabey Jr, Charlotte D Owens, Alfred Poindexter, Elizabeth E Puscheck, Henry Rodriguez-Ginorio, James A Simon, Ahmed M Soliman, Elizabeth A Stewart, Nelson B Watts, Ozgul Muneyyirci-Delale
• Journal: The New England journal of medicine (N Engl J Med) Vol. 382 Issue 4 Pg. 328-340 (01 23 2020) ISSN: 1533-4406 [Electronic] United States
• PMID: 31971678 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Massachusetts Medical Society.

Chemical References

• Estrogens
• Hydrocarbons, Fluorinated
• Pyrimidines
• Gonadotropin-Releasing Hormone
• Estradiol
• elagolix

Topics

• Adult
• Bone Density (drug effects)
• Double-Blind Method
• Drug Therapy, Combination
• Estradiol (therapeutic use)
• Estrogens (therapeutic use)
• Female
• Gonadotropin-Releasing Hormone (antagonists & inhibitors)
• Hot Flashes (chemically induced)
• Humans
• Hydrocarbons, Fluorinated (adverse effects, therapeutic use)
• Leiomyoma (complications)
• Menorrhagia (drug therapy, etiology)
• Middle Aged
• Pyrimidines (adverse effects, therapeutic use)
• Quality of Life
• Severity of Illness Index
• Surveys and Questionnaires