Relugolix combo improves uterine fibroid symptoms regardless of fibroid location

Combination therapy with relugolix (once daily relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) leads to improvement in heavy menstrual bleeding (HMB) and in other uterine fibroid (UF)-related symptoms independent of the location of the largest fibroid, results of a recent study have shown.

“In the phase III, replicate institutional review board-approved LIBERTY 1 and 2 studies, relugolix combination therapy improved UF-associated HMB, pain, and quality of life (QoL),” said lead author Roberta Venturella, MD, from the University Magna Graecia in Catanzaro, Italy.

The study was presented at the recently concluded 2022 Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists (ACOG).

Venturella and colleagues examined the impact of location (submucosal, intramural, or subserosal) of the largest fibroid on treatment outcomes through 24 weeks. They randomized premenopausal women to relugolix combination therapy or placebo for 24 weeks.

Using ultrasound, the investigators defined the location of the largest fibroid, excluding FIGO type 0/1 fibroids. They measured menstrual blood loss (MBL) volume by alkaline hematin method (responders: MBL volume, 80 mL and 50-percent reduction from baseline over the last 35 days of treatment).

In this post hoc analysis, the Numerical Rating Scale and UF-QoL Questionnaire (Symptom Severity) were used to assess pain and other UF-related symptoms.

The largest fibroid was categorized by location in the relugolix combination therapy (N5253) and placebo (N5256) groups as follows: subserous (N550 and N558), intramural (N5255 and N5130), submucosal (N546 and N543), or “other/unknown” (N5119 and N5106). Both groups had similar baseline characteristics, including MBL volume, pain, and QoL scores. [ACOG 2022, abstract A77]

In all fibroid subgroups, women on relugolix combination therapy showed comparable responder rates at week 24 that were higher than with placebo (76.0 percent, 79.1 percent, 80.4 percent, and 65.6 percent vs 24.1 percent, 16.2 percent, 14.0 percent, and 16.0 percent, respectively; p=0.0001).

The relugolix combination therapy group also had significant reductions in MBL volume, UF-associated pain, and symptom severity across all subgroups relative to the placebo group.

Bleeding patterns

In another study presented at ACOG 2022 by lead author Andrea S. Lukes, MD, from the Carolina Women’s Research and Wellness Center in Durham, England, many women with UF-associated HMB who received relugolix combination therapy for up to 52 weeks reported amenorrhea, which was defined as lack of bleeding for two consecutive visits (approximately 56 days).

A total of 163 women received relugolix combination therapy for up to 52 weeks, of whom 70.6 percent achieved amenorrhea, while 9.2 percent and 20.2 percent reported cyclic or irregular patterns, respectively. Of the 15 patients with cyclic bleeding, nine had spotting or light-to-moderate bleeding. Similar intensity was noted among 33 women with irregular bleeding. [ACOG 2022, abstract A78]

In this study, Lukes and colleagues analysed bleeding patterns and bleeding intensity reported in a daily diary through 52 weeks/end of treatment. They quantified MBL using the alkaline hematin method. Bleeding pattern was defined as cyclic (3‒12 days of bleeding) or irregular (did not meet the definition of amenorrhea or cyclic bleeding).