Elagolix with add-back therapy effective for premenopausal heavy menstrual bleeding associated with fibroids

Référence

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.

Sommaire

Elagolix is a gonadotropin-releasing hormone antagonist that has a short half-life and can quickly suppress sex hormones with rapid reversal when the drug is discontinued. In this study, a combined report of two phase 3 trials, a total of 790 premenopausal women with sonographically confirmed uterine fibroids and at least 80 mL of menstrual blood loss per cycle over 2 cycles were identified. The 2 study designs were identical and the populations were very similar: mean age 42 years, approximately two-thirds black race, and mean body mass index of approximately 34 kg/m2. Participants were randomized into 1 of 3 groups in a 2:1:1 ratio using a double-dummy design: (1) elagolix with add-back hormone therapy designed to avert the hypoestrogenic adverse effects of the drug (estradiol 1 mg plus norethindrone acetate 0.5 mg), (2) elagolix plus placebo add-back therapy, and (3) placebo for both. Groups were balanced at the start of the 6-month study, and analysis was by modified intention to treat for all women receiving at least one dose of the study drug. Women could not use hormonal or intrauterine device contraception during the study. At 6 months, 78% of women overall had completed the study, which indicates a fairly high dropout rate. The primary outcome was clinical response defined as monthly menstrual blood loss of less than 80 mL in the final month of the study plus at least a 50% reduction in blood loss from baseline to the final month. At 6 months, in the first study this was achieved by 84% in the elagolix-alone group, 68.5% in the elagolix with add-back therapy, and 8.7% in the placebo group. Results were similar in the second study (77% vs 77% vs 10% respectively. The women in both elagolix groups also experienced clinically and statistically significant reductions in a disease-specific symptom severity score compared with women taking placebo. Adverse effects were common, with rates of hot flashes of 43% to 64% in the elagolix-alone group and 20% in the elagolix with add-back therapy group; headache and night sweats were also common in the elagolix-alone group, and nausea was common in the elagolix with add-back therapy group. The elagolix-alone group had larger decreases in bone mineral density than the placebo or elagolix with add-back therapy groups. The list of author conflicts of interest in this industry-sponsored trial runs to more than 500 words. The trial sponsor AbbVie designed the trial, analyzed the data, and their employees wrote the first draft.