Impact of Relugolix Combination Therapy on Functioning and Quality of Life in Women with Endometriosis-Associated Pain.

OBJECTIVE: To evaluate the effect of relugolix combination therapy (relugolix CT; 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethisterone acetate) for up to 2 years in the SPIRIT long-term extension (LTE) study on functioning and health-related quality of life (QoL), using the Endometriosis Health Profile (EHP)-30 questionnaire, and assess how changes in QoL domains correlated with improvements in dysmenorrhea and non-menstrual pelvic pain (NMPP). DESIGN: Long-term extension (LTE) study of the SPIRIT phase 3 trials. SUBJECTS: Premenopausal women with moderate-to-severe endometriosis pain who previously completed the randomized SPIRIT trials were eligible to enroll in an 80-week LTE where all women received relugolix CT. INTERVENTIONS: Relugolix combination therapy (relugolix CT: relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) MAIN OUTCOME MEASURE(S): Least square (LS) mean changes in the EHP-30 domain and total scores from baseline (pivotal) were analyzed using a mixed-effects model. Results up to104 weeks are reported by pivotal trial treatment group with a focus on the relugolix CT group (ie, relugolix CT or placebo for 24 weeks, or delayed relugolix CT [relugolix 40 mg monotherapy for 12 weeks, followed by relugolix CT for 12 weeks]). In addition, the relationships between changes in dysmenorrhea and NMPP and changes in EHP-30 scores were assessed. RESULTS: In the 277 women treated with relugolix CT, LS mean EHP-30 pain domain scores improved by 57.8% (LS mean change:-32.8; 95% CI:-35.5, -30.1), 66.4% (LS mean change:-37.7; 95% CI:-40.3,-35.0); and 72.2% (LS mean change:-41.3; 95% CI:-43.9,-38.7) at Weeks 24, 52, and 104, respectively. The proportions of women with clinically meaningful improvement on the EHP-30 pain domain were 75.9%, 83.6% and 88.6% at weeks 24, 52, and 104, respectively. Non-pain EHP-30 domain and total scores likewise improved. A positive correlation between changes in dysmenorrhea/NMPP and all EHP -30 domain scores was observed. Results were similar for the delayed relugolix CT and placebo→relugolix CT groups. CONCLUSIONS: Sustained reduction of endometriosis-associated pain with relugolix CT observed up to 104 weeks was accompanied by improvements in functioning and health-related QoL. These findings complement the results of the pivotal SPIRIT trials, which showed relugolix combination therapy significantly reduced dysmenorrhea, non-menstrual pelvic pain (NMPP) and dyspareunia vs placebo in premenopausal women with endometriosis-associated pain.