For women with uterine fibroids and anemia, oral elagolix combined with hormonal add-back therapy was found to be both safe and effective in the management of heavy menstrual bleeding (>80 mL), according to study results published in the New England Journal of Medicine.1
Researchers conducted 2 phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to assess the efficacy and safety of elagolix with add-back therapy (1 mg estradiol and 0.5 mg norethindrone daily) in premenopausal women aged 18 to 51 years who had an ultrasonography-confirmed diagnosis of uterine fibroids and heavy menstrual bleeding (>80 mL of blood loss/cycle for at least 2 separate menstrual cycles). In clinical trials of elagolix for the management of endometriosis, add-back hormone replacement therapy was needed to counter the hypoestrogenic effects of the gonadotropin-releasing hormone (GnRH) antagonist, including loss in bone mineral content.2
UF-1 was conducted from December 2015 through December 2018, and UF-2 was conducted from February 2016 through January 2019. Each trial consisted of a period of washout of hormonal medication (if applicable), a screening period (2.5-3.5 months), a 6-month treatment period, and a 12-month follow-up period. Only the results of the 6-month treatment period were reported. Women were randomly assigned within 10 days after the start of their menses to receive elagolix 300 mg twice per day with add-back therapy, elagolix 300 mg twice daily alone, or placebo.
The primary end point was menstrual blood loss of <80 mL during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month. Women were asked to report their symptoms during the previous 4 weeks on the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire.
A total of 413 women in UF-1 and 378 in UF-2 underwent randomization; all patients but 1 in UF-1 received elagolix or placebo and were included in the efficacy and safety analysis. A total of 328 women in UF-1 (79.6%) and 289 in UF-2 (76.5%) completed the 6-month treatment period.
Significantly greater percentages of women who received elagolix with add-back therapy (68.5% of 206 women in UF-1 and 76.5% of 189 women in UF-2) reported menstrual blood loss of <80 mL during the 6-month treatment period and at least a 50% reduction in menstrual blood loss from baseline to the final month compared with women who received placebo (8.7% of 102 women in UF-1 and 10% of 94 women in UF-2). Among women who received elagolix alone, 84.1% of 104 women in UF-1 and 77% of women in UF-2 met the primary end point.
More than 60% of the women in each trial group reported at least 1 adverse event; most adverse events were considered by the investigators to be mild or moderate in severity. In UF-1 and UF-2, hot flushes were significantly more common with elagolix plus add-back therapy (20.4% and 19.6%, respectively) and with elagolix alone (64.4% and 43%, respectively) than with placebo (8.8% and 4%, respectively). “[I]n UF-1 and UF-2, night sweats were significantly more common with elagolix alone (26.9% and 25%, respectively) than with placebo (2.9% and 5%, respectively),” the authors wrote.
In both trials, “the risk of heavy menstrual bleeding among premenopausal women with uterine fibroids was significantly lower among women who received elagolix at a dose of 300 mg twice daily with add-back therapy for 6 months than among those who received placebo,” they concluded.
Disclosure: Both UF 1 (ClinicalTrials.gov identifier: NCTO2654054) and UF 2 (ClinicalTrials.gov identifier: NCTO2691494) were funded by AbbVie, maker of Orilissa (elagolix). Financial disclosures of the individual authors can be found in the published article.
1. Schlaff WD, Ackerman RT, Al-Hendy A, et al. Elagolix for heavy menstrual bleeding in women with uterine fibroids. N Engl J Med. 2020;382(4):328-340.