Relugolix combination therapy (relugolix-CT) improves uterine fibroid-associated heavy menstrual bleeding (HMB) in Black women, according to a recent study published in the American Journal of Obstetrics & Gynecology.
Takeaways
- The study indicates that relugolix combination therapy (relugolix-CT) is effective in managing heavy menstrual bleeding associated with uterine fibroids in Black women.
- Black women are disproportionately affected by uterine fibroids, experiencing symptoms such as pain, infertility, anemia, increased urinary frequency, and heavy menstrual bleeding at a higher rate compared to other racial groups.
- The therapy demonstrates significant efficacy in reducing menstrual blood loss and improving symptom burden in Black women with uterine fibroids, with manageable adverse events such as hot flush, headache, and hypertension.
- The study reports high treatment completion rates among Black participants and significant improvement in menstrual bleeding reduction, anemia, uterine, and fibroid volumes, indicating favorable treatment outcomes.
- Reductions in bone mineral density are minimal, indicating the treatment has a favorable risk-benefit profile in this population.
Multiple risk factors have been associated with uterine fibroids (UFs), including lifestyle, age, race, and genetic predisposition. The prevalence of UFs is increased 3-fold to 4-fold in Black women vs other races, with an estimated lifetime UF prevalence of up to 89%.
Up to 50% of Black women experience pain, infertility, anemia, increased urinary frequency, and HMB. This population more often undergoes open hysterectomy and has a reduced likelihood of being offered minimally invasive approaches.
Relugolix, a gonadotropin-releasing hormone receptor antagonist, can be used for UF management through relugolix-CT. This therapy has received approval for managing UF-associated HMB in the United States with data indicating improved symptom burden compared to placebo and preserved bone mineral density (BMD).
Despite increased symptom burden among Black women, there is lacking data on the impact of UF treatments in this population. To determine outcomes of relugolix-CT among Black women, investigators conducted a subgroup analysis of the LIBERTY 1 and 2 studies and the LIBERTY LTE study.
Participants included premenopausal women aged 18 to 50 years diagnosed with UFs through ultrasound and with HMB, defined as 2 cycles of menstrual blood loss (MBL) of 80 mL or more or 1 cycle of MBL of 160 mL or more.
In the LIBERTY 1 and 2 trials, patients received either 24 weeks of once-daily relugolix-CT, 24 weeks of placebo, or 12 weeks of delayed monotherapy relugolix-CT followed by 12 weeks of relugolix-CT. During the LIBERTY LTE trial, eligible patients who completed the LIBERTY 1 or 2 trials received up to 28 weeks of once-daily relugolix-CT.
Patients attended study visits every 4 weeks from baseline through week 52. The proportion of Black women at week 52 with an MBL volume below 80 mL and 50% or more reduction in MBL from baseline to the last 35 days of treatment was measured as the primary efficacy endpoint. This was measured using the alkaline hematin method.
The incidence of adverse events and BMD change at the lumbar spine, total hip, and femoral neck were reported as safety endpoints. Common Terminology Criteria for Adverse Events was used to grade adverse events.
There were 477 women included in the Liberty LTE, 50.5% of whom were Black. Completed treatment was reported in 75.1% of Black participants and anemia at baseline in 43.6%. Black patients had a mean baseline body mass index of 33.6 kg/m2, MBL volume of 243.2 mL, uterine volume of 490.5 cm3, and largest fibroid volume of 94.8 cm3.
In the relugolix-CT group, 82.9% of Black participants met the primary endpoint at week 52 or end of treatment, vs 70.8% in the placebo to relugolix-CT group and 78.1% in the delayed relugolix-CT group. The mean percentage change in MBL volume from baseline to week 52 for Black women in the relugolix-CT group was −85.0%.
Amenorrhea was reported in 64.3% of women and improvement in baseline anemia in 59.1%. A mean reduction in UF and uterine volumes of −21.3% and −10.0%, respectively, were reported in the relugolix-CT group. Reduced symptom burden and improved health related quality of life were also reported.
Adverse events were reported in 30% of the relugolix-CT group, 51% of the placebo to relugolix-CT group, and 63% of the delayed relugolix-CT group. Hot flush was the most common adverse event, followed by headache and hypertension.
In the relugolix-CT group, 5.7% of women reported a serious adverse event, with 1.4% reporting events leading to treatment discontinuation. In the placebo to relugolix-CT and delayed relugolix-CT groups, adverse events leading to treatment discontinuation were reported in 6.4% and 2.4%, respectively.
Reductions in lumbar spine BMD form baseline to week 52 were 1.2% in the relugolix-CT group and 0.9% in the placebo to relugolix-CT group. In the delayed relugolix-CT group, a reduction of 2.6% was observed during monotherapy, which stabilized to 2.3% by week 52.
These results indicated safety and efficacy from relugolix-CT in treating UF-associated HMB in Black women. Investigators concluded these results are comparable to the overall population of the LIBERTY studies.
Reference
Stewart EA, Al-Hendy A, Lukes AS, et al. Relugolix combination therapy in Black/African American women with symptomatic uterine fibroids: LIBERTY Long-Term Extension study. Am J Obstet Gynecol. 2024;230:237.e1-11. doi:10.1016/j.ajog.2023.10.030
