Relugolix combination therapy effective, safe for premenopausal women with endometriosis

Key takeaways:

• Relugolix combination therapy was associated with improved endometriosis pain for up to 2 years.
• Over 2 years, the therapy was well tolerated with a safety profile consistent with prior studies.

Relugolix combination therapy may be an effective and safe long-term treatment option for premenopausal women with endometriosis and nonmenstrual pelvic pain, researchers reported in Human Reproduction.

“Relugolix combination therapy was developed as a once-daily oral treatment for endometriosis-associated pain or symptomatic uterine fibroids to provide a treatment option that could be used for a longer duration,” Christian M. Becker, MD, co-director of the Oxford Endometriosis Care and Research Centre, England, and colleagues wrote. “In USA, relugolix combination therapy is approved for management of heavy menstrual bleeding associated with uterine fibroids as well as for treatment of moderate to severe pain associated with endometriosis.”

In the 24-week phase 3, randomized, double-blind, placebo-controlled SPIRIT 1 and 2 studies, premenopausal women with confirmed endometriosis who reported moderate to severe dysmenorrhea and nonmenstrual pelvic pain received once-daily relugolix combination therapy with relugolix 40 mg, estradiol 1 mg and norethindrone acetate 0.5 mg (Myfembree, Myovant Sciences).

Becker and colleagues conducted a multinational, open-label, single-arm, long-term efficacy and safety extension study in which participants from the SPIRIT studies received up to an additional 80 weeks of therapy. At 104 weeks, researchers evaluated results by treatment group based on participants’ original randomization in SPIRIT studies to either relugolix combination therapy, relugolix 40 mg monotherapy for 12 weeks followed by relugolix combination therapy, or placebo for 24 weeks followed by relugolix combination therapy.

Primary outcomes were responders at 52 and 104 weeks, defined as those who achieved a predefined, clinically meaningful reduction of 2.8 points for dysmenorrhea and 2.1 points for nonmenstrual pelvic pain from baseline in the numerical rating scale (NRS), with higher scores indicating worse pain. Secondary outcomes included change from baseline in 30-item Endometriosis Health Profile (EHP-30) pain domain scores, NRS scores for dysmenorrhea, nonmenstrual pelvic pain, dyspareunia and overall pelvic pain and analgesic/opioid use.

Overall, 681 women completed 52 weeks and 501 completed 104 weeks of treatment in the extension study. The 277 women who received relugolix combination therapy in SPIRIT 1 and 2 and the extension study reported sustained improvements in endometriosis-associated pain for up to 104 weeks. Of these women, 84.8% were dysmenorrhea responders and 75.8% were nonmenstrual pelvic pain responders, the researchers reported.

Women who received relugolix combination therapy in each study also reported decreased dyspareunia and improved function as assessed by the EHP-30 pain domain for up to 104 weeks. At 104 weeks, 91% of women were opioid-free and 75% were analgesic-free, according to the researchers.

Over 104 weeks, relugolix combination therapy was well tolerated with a safety profile consistent with results from SPIRIT 1 and 2. Efficacy and safety were consistent for women who received placebo for 24 weeks followed by relugolix combination therapy and relugolix 40 mg monotherapy for 12 weeks followed by relugolix combination therapy, the researchers wrote.

In addition, bone mineral density plateaued at 32 weeks after initial least squares mean bone mineral density loss of less than 1% at 24 weeks in SPIRIT 1 and 2, and was sustained for up to 104 weeks.

“Future areas of study may include examination of the effect of long-term medical control of endometriosis symptoms with relugolix combination therapy on the potential to minimize the need for repeated surgeries,” the researchers wrote.