Elagolix for heavy menstrual bleeding in women with uterine fibroids

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, Jin Hee Kim, Ran Liu, R. Garn Mabey, Charlotte D. Owens, Alfred Poindexter, Elizabeth E. Puscheck, Henry Rodriguez-Ginorio, James A. Simon, Ahmed M. Soliman, Elizabeth A. Stewart, Nelson B. WattsOzgul Muneyyirci-Delale

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7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)328-340
Number of pages13
JournalNew England Journal of Medicine
Volume382
Issue number4
DOIs
StatePublished - Jan 23 2020

ASJC Scopus subject areas

  • Medicine(all)

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    Schlaff, W. D., Ackerman, R. T., Al-Hendy, A., Archer, D. F., Barnhart, K. T., Bradley, L. D., Carr, B. R., Feinberg, E. C., Hurtado, S. M., Kim, J. H., Liu, R., Garn Mabey, R., Owens, C. D., Poindexter, A., Puscheck, E. E., Rodriguez-Ginorio, H., Simon, J. A., Soliman, A. M., Stewart, E. A., ... Muneyyirci-Delale, O. (2020). Elagolix for heavy menstrual bleeding in women with uterine fibroids. New England Journal of Medicine, 382(4), 328-340. https://doi.org/10.1056/NEJMoa1904351