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Relugolix combination therapy (CT) is associated with maintained low menstrual bleeding volume in women with symptomatic uterine fibroids (UFs), according to a recent study published in the American Journal of Obstetrics & Gynecology.
- The study suggests that relugolix CT is associated with sustained low menstrual bleeding volume in women with symptomatic uterine fibroids.
- The phase 3 randomized withdrawal study (RWS) showed that the efficacy of relugolix CT was maintained for up to 104 weeks, with a significant proportion of women experiencing a sustained reduction in menstrual blood loss below 80 mL.
- The therapy demonstrated not only a reduction in heavy menstrual bleeding but also a high rate of amenorrhea, indicating a positive impact on the quality of life for women with uterine fibroids.
- The study reported low discontinuation rates for both the relugolix CT and placebo groups, suggesting good tolerability. Adverse events were generally mild to moderate, and minimal bone mineral density changes were observed over a 1-year period.
- Patients receiving Relugolix CT showed a significantly lower risk of relapse of heavy menstrual bleeding compared to the placebo group, indicating sustained efficacy.
UFs are uterine tumors commonly seen in premenopausal women and are often treated through hysterectomy, a surgical procedure with potential significant and long-lasting adverse effects. Available medical treatments for UFs often have limited symptom relief or tolerability issues, preventing long-term use.
A medical therapy for UFs with long-term symptom reduction and preservation of bone mineral density (BMD) is necessary. Relugolix CT was designed to improve UFs symptoms with minimal BMD loss risk and is currently approved for treating symptoms associated with UFs.
Investigators conducted a study reporting the results of the phase 3 randomized withdrawal study (RWS) assessing the durability of relugolix CT up to 104 weeks. Participants included premenopausal women aged 18 to 50 years diagnosed with uterine leiomyomas and with a recorded menstrual blood loss (MBL) of 80 mL or more per cycle for 2 cycles or 160 mL or more for 1 cycle.
The 28-week LIBERTY long-term extension (LTE) study was offered to patients with 24 weeks of completed treatment in one of the pivotal studies. Treatment efficacy was measured by quantitative changes in MBL, with a blood loss of 80 mL per cycle or more used to define heavy menstrual bleeding (HMB).
Participants were randomized 1:1 to receive placebo or relugolix CT for up to 52 weeks. Visits were completed at baseline and every 4 weeks until the end of treatment, and hemoglobin concentrations were measured during visits.
Long-term efficacy was measured as the proportion of women with an MBL volume below 80 mL maintained through week 76. HMB was defined by a measurement of 80 mL or more. Secondary efficacy outcomes included time to HMB, proportion of women with MBL under 80 mL through week 104, and proportion of women with amenorrhea.
Adverse events, weight, vital signs, clinical laboratory tests, physical and gynecologic examinations, resumption of menses after treatment completion, and BMD using dual-energy x-ray absorptiometry evaluation at week 104 were evaluated to determine treatment safety.
There were 229 women randomized in the RWS. Twenty-four weeks of treatment were completed by over 80% of women in both groups, and 52 weeks by 77.4% and 75.4% in the relugolix CT and placebo groups, respectively. Similar rates of discontinuation were observed between the relugolix CT and placebo groups, at 3.5% and 2.6%, respectively.
Participants were aged a mean 43.8 years and had an average body mass index of 31.0 kg/m2. Of women, 50.4% were White, 46.5% Black, and 25.9% Hispanic. A high burden of disease was observed at the pivotal studies baseline, but not the RWS baseline.
A sustained MBL volume under 80 mL through week 76 was reported in 78.4% of the relugolix CT group and 15.1% of the placebo group. For patients receiving 104 weeks of treatment, sustainability was reported in 79.13% of the relugolix CT group and 16.28% of the placebo group.
Being amenorrheic at week 76 was reported in 57.4% of women receiving relugolix CT and 13.3% of women receiving placebo. At week 104, these rates were 58.3% and 10.6%, respectively.
A relapse of HMB by week 104 was reported in 88.3% of women receiving placebo with a median relapse time of 5.9 weeks. In comparison, only 30.2% of patients in the relugolix CT group relapse, below the 50% necessary to measure a median relapse time. The risk of relapse was reduced by 87% in patients receiving relugolix CT vs placebo.
One or more adverse events were reported in 61.4% of the overall study population, most of which had mild to moderate severity. Minimal BMD changes were observed across a 1-year period, with a mean change of 0.8% at the lumbar spine and 0.3% at the total hip for women in the relugolix CT group.
These results indicated safety and efficacy from relugolix CT treatment in women with UFs. Investigators recommended future research evaluate relugolix CT beyond 2 years.
Al-Hendy A, Venturella R, Arjona Ferreira JC, et al. LIBERTY randomized withdrawal study: relugolix combination therapy for heavy menstrual bleeding associated with uterine fibroids. Am J Obstet Gynecol. 2023;229:662.e1-25. doi:10.1016/j.ajog.2023.08.030