An oral dose of elagolix with hormonal add-back therapy had a better effect than elagolix alone or placebo.
William Schlaff, MD
Women with uterine fibroids who used elagolix (Orilissa) with add-back therapy saw a reduction in heavy menstrual bleeding.
Abnormal bleeding is 1 of the most common indications of uterine fibroids and hysterectomy in the US, lead investigator William Schlaff, MD, a reproductive endocrinology and infertility physician at Jefferson University, told HCPLive® in an interview. The oral dose of elagolix with hormonal add-back therapy had a better effect than injectable medications.
Schlaff and colleagues from academic medical institutions across the US conducted 2 identical, double-blind, randomized, placebo-controlled, six-month phase 3 trials—Elaris uterine fibroids 1 (UF-1) and 2 (UF-2). The investigators evaluated the safety and efficacy of elagolix at a dose of 300 mg 2 times a day with hormonal add-back therapy in women with bleeding due to fibroids.
In roughly 70% of women, elagolix reduced abnormal bleeding, Schlaff said.
UF-1 and UF-2 each consisted of a 2.5—3.5 month screening period, a six-month treatment period, and a twelve-month follow-up period. The investigators randomly assigned the women to either receive a 300 mg dose of elagolix with add-back therapy (estradiol, 1 mg, and norethindrone acetate, .5 mg, once daily) twice a day, a 300 mg dose of elagolix alone twice daily, or placebo in a matched, double-blind, double-dummy manner.
The primary end point of the research was menstrual blood loss < 80 ml during the final month and at least a 50% reduction in menstrual blood loss form baseline to the last month. Some secondary end points included the change in menstrual blood loss from baseline to the end, the percentage of women who had suppression of bleeding at the end of the study, and the change from baseline in blood loss at 6 months.
Eligible women were premenopausal, between 18—51 years old at the time of screening, and had ultrasonography-confirmed uterine fibroids and heavy menstrual bleeding diagnoses.
Women reported their symptoms over the previous 4 weeks on the Uterine Fibroid Symptom and Quality of Life questionnaire. The questionnaire included a symptom severity score (0—100; higher scores indicated increased severity) and a health-related quality-of-life total score, which was the sum of scores on 6 subscales—concern, activities, energy and mood, control, self-consciousness, and sexual function. The scores ranged from 0–100, with higher scores associated with a better quality of life.
Nearly 800 women in UF-1 and UF-2 received either 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, compared to women who received placebo (8.7% of 102 women in UF-1 and 10% of 94 women in UF-2; P <.001). Among those who received only elagolix, 84.1% of 104 women in UF-1 and 77% of 95 in UF-2 met the criteria for the primary end point.
Elagolix with add-back therapy resulted in significant improvements in secondary outcomes, compared with placebo. Improvements included a greater reduction in menstrual blood loss from baseline to the final month, a higher percentage of women with suppression of bleedings at the final month, and a greater reduction in menstrual blood loss from baseline to 6 months and 3 months.
The mean change in symptom severity—with higher scores indicating increased severity—from baseline to 6 months in women who received elagolix with add-back therapy was −33.2±1.61 in UF-1 and −41.4±1.60 in UF-2. For those with placebo the changes were −10.3±2.25 and −7.9±2.28, respectively.
On the quality of life score—with higher scores indicating better quality of life—the mean change for those who had elagolix with add-back therapy was 38.0±1.62 in UF-1 and 42.0±1.62 in UF-2. Among those who received placebo, the changes were 10.9±2.27 and 6.5±2.32.
Oral therapies, rather than injectables, have more rapid onset and are easier to stop, Schlaff said. Injectables last for a longer time—1 or 3 months—and then gradually go away. With an oral medication taken 2 times a day, there is more control by the patient.
“Having a medical therapy that is rapid onset produced significant improvement in bleeding patterns and quality of life without loss of bone and with very mild or modest increase in side effects,” he said.
Findings of an extension study will soon be presented. In the analysis, the investigators extended the treatment to 12 months rather than 6 to see if the treatment can help for up to a year. Other aspects of the analysis related to the effect of medications on symptoms other than heavy bleeding.
The study, “Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids,” was published online in The New England Journal of Medicine.