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NASHVILLE -- Elagolix (Orilissa) oral therapy, which is already approved for the treatment of endometriosis, showed significant reductions in menstrual bleeding among women with uterine fibroids in a pair of phase III trials, but with added side effects.

Women with uterine fibroids treated for up to 6 months with elagolix and an add-back therapy (estradiol 1 mg/norethindrone acetate 0.5 mg QD, like a birth control pill) experienced significant reductions in menstrual blood loss at the final month of therapy compared to those randomized to placebo, according to William Schlaff, MD, of Thomas Jefferson University in Philadelphia.

The findings were reported during a presentation at the American College of Obstetricians and Gynecologists (ACOG) annual meeting. The add-back therapy is meant to attenuate decreases in bone mineral density and other "hypoestrogenic side effects" -- such as hot flushes and night sweats -- associated with elagolix alone, Schlaff and co-authors explained in their abstract. Elagolix, a gonadotropin-releasing hormone (GnRH) antagonist that results in a dose-dependent suppression of gonadotropins and ovarian sex steroids, combined with add-back therapy had previously demonstrated a reduction in menstrual blood loss in a phase IIb study, Schlaff said.

Charles Ascher-Walsh, MD, of Icahn School of Medicine at Mount Sinai in New York City, who was not involved with the research, said there aren't a lot of medication options for fibroids. Patients have used hormonal intrauterine devices (IUDs), and there is some evidence that vitamin D and green tea extract can suppress fibroid growth, he said.

But Ascher-Walsh added that side effects of this therapy, which can mimic symptoms of menopause, are a real drawback, and given that uterine fibroids have more of a "short-term effect" on women's lives, some patients may not feel like the therapy is worth the side effects.

"Women are willing to put up with [fibroids] for years, so the idea of taking a medication that will have significant side effects I don't think is often that popular. [Symptoms] are not as dramatic as the debilitating pain from endometriosis," he said.

Study Details

Researchers conducted two parallel randomized trials (ELARIS UF-1 with 415 patients, and ELARIS UF-2 with 378 patients) in a 1:1:2 ratio for women to receive placebo, 300 mg of elagolix alone, or 300 mg of elagolix plus add-back therapy for a treatment period of 6 months. Participants were pre-menopausal women ages 18-51 with heavy menstrual bleeding of at least 80 mL of menstrual blood loss per cycle and an ultrasound-confirmed diagnosis of uterine fibroids. "Menstrual products" were collected on a daily basis, Schlaff said.

The primary endpoint was defined as the percentage of women who had menstrual blood loss volume of less than 80 mL during the final month of therapy and ≥50% reduction in menstrual blood loss volume from baseline to the final month.

Overall, patients were a mean age of about 42 across the two trials, and about 70% were black, with a mean BMI of around 33-34. Schlaff noted that they had "significant symptoms related to the disease," with a quality of life (QOL) score around 40. "Most women have a QOL score closer to 80," he said.

The authors concentrated on the elagolix with add-back therapy group in each trial, noting that this group met the primary endpoint (68.5% and 76.5% in UF-1 and UF-2, respectively) and produced a significantly higher portion of patients with reduced menstrual bleeding in the final month compared to placebo. They also noted that a significantly greater proportion of women receiving elagolix with add-back therapy had suppression of bleeding (no bleeding, spotting) in the final month versus placebo, and that elagolix with add-back therapy improved health-related QOL scores from baseline.

Examining safety, 68% to 76% of patients in the elagolix with add-back therapy group reported any adverse event, with the most common being hot flushes and night sweats. However, the authors noted that the proportion of women reporting any adverse events was lower than the elagolix alone group (76% to 90%), and fewer women in the elagolix with add-on group had hot flushes and night sweats. By comparison, 63% to 70% of placebo patients reported any adverse event. Treatment-related adverse events were more rare in the placebo compared with elagolix plus add-back therapy groups, respectively (38% vs 51% in UF-1; 36% vs 50% in UF-2).

The elagolix plus add-back group also reduced the likelihood of bone mineral density decreases compared with elagolix alone, the authors said.

Nevertheless, Ascher-Walsh said that for many, the "go-to" treatment for uterine fibroids is a hysterectomy, so it's nice for doctors to have additional options for therapy in these patients.

"Plenty of women [with fibroids] won't want [elagolix] because it's a hormone and it will affect the way they feel, some will try it with significant side effects and want to stop, and others will be successful with it. But it's not the savior for women with fibroids," he said.

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