Blood loss due to uterine fibroids reduced at 2 years with relugolix combination therapy

Key takeaways:

• More women in the relugolix group maintained menstrual blood loss volume less than 80 mL vs. placebo.
• More women in the relugolix group achieved or maintained amenorrhea at 76 and 104 weeks vs. placebo.

At 2 years, women who had received relugolix combination therapy for 52 weeks and then withdrew therapy continued to have less menstrual blood loss and pain caused by uterine fibroids, researchers reported.

“Relugolix combination therapy has been approved for the treatment of symptoms associated with uterine fibroids and moderate to severe pain associated with endometriosis,” Ayman Al-Hendy, MD, PhD, professor of obstetrics and gynecology at the University of Chicago, and colleagues wrote. “Here we report results of the phase 3 randomized withdrawal study, the last in a suite of studies in the phase 3 uterine fibroid clinical program to assess durability of treatment effect and tolerability for up to 104 weeks with relugolix combination therapy.”

Al-Hendy and colleagues conducted the phase 3 LIBERTY randomized withdrawal study, published in the American Journal of Obstetrics & Gynecology, of once-daily combination therapy of relugolix (Myfembree, Myovant Sciences) 40 mg, estradiol 1 mg and norethindrone acetate 0.5 mg. Researchers assessed the treatment in 229 women with uterine fibroid-associated heavy menstrual bleeding who completed the 24-week LIBERTY 1 or 2 trials and the long-term extension study with menstrual blood loss volume of less than 80 mL and a 50% or greater reduction from baseline to 48 weeks. All participants were randomly assigned to relugolix combination therapy (n = 115) or placebo (n = 114) for 52 weeks.

The primary outcome was the proportion of women who maintained menstrual blood loss volume less than 80 mL through 76 weeks. Secondary outcomes included time to menstrual blood loss volume of 80 mL or more, the proportion of women who maintained a menstrual blood loss volume of less than 80 mL through 104 weeks, the proportion of women achieving or maintaining amenorrhea at 76 weeks, and change in Uterine Fibroid Symptom and Quality of Life bone mineral density and symptom severity scores.

Overall, 76.7% of women who received the study drug completed the withdrawal study. At 76 weeks, 78.4% of women who received relugolix combination treatment maintained menstrual blood loss volume of less than 80 mL compared with 15.1% of women in the placebo group (P < .0001). At 104 weeks, 69.8% of women who received relugolix combination therapy maintained menstrual blood loss volume of less than 80 mL compared with 11.8% of women in the placebo group (P < .0001).

In addition, 88.3% of women in the placebo group relapsed with heavy menstrual bleeding at 104 weeks with a median time to relapse of 5.9 weeks. Of the 89 women in the placebo group who relapsed and received open-label rescue treatment, 87 responded to relugolix combination therapy.

Researchers reported that 57.4% of women who received relugolix combination therapy achieved or maintained amenorrhea vs. 13.3% of women in the placebo group at 76 weeks (P < .0001), and 58.3% of women achieved or maintained amenorrhea vs. 10.6% of women in the placebo group at 104 weeks (P < .0001).

Overall, relugolix combination therapy was generally well tolerated with no new identified safety signals, according to the researchers. The adverse event profile over the second year of treatment was consistent with that reported through the first year of treatment with relugolix combination therapy.

Bone mineral density remained stable among women who received relugolix combination therapy from 52 to 104 weeks of treatment, and bone mineral density was preserved among women who were continuously treated with relugolix combination therapy up to 2 years.

“Together, these clinical outcomes provide information regarding longer-term management strategies for heavy menstrual bleeding associated with uterine fibroids and may help support patient demands and choice for uterus-preserving treatment,” the researchers wrote.