目的:评估relugolix联合治疗的效果(relugolixCT;40mgrelugolix,1毫克雌二醇,和0.5mg醋酸炔诺酮)在SPIRIT长期扩展(LTE)研究中对功能和健康相关的生活质量(QoL)进行长达2年的研究,使用子宫内膜异位症健康状况(EHP)-30问卷,并评估QoL域的变化如何与痛经和非月经性盆腔疼痛(NMPP)的改善相关。
方法:SPIRIT3期试验的长期扩展(LTE)研究。
方法:患有中度至重度子宫内膜异位症疼痛的绝经前女性,先前完成了随机SPIRIT试验,有资格参加为期80周的LTE,所有女性均接受relugolixCT。
方法:Relugolix联合治疗(relugolixCT:relugolix40mg,雌二醇1毫克,醋酸noretinrone0.5mg)主要结果测量(S):使用混合效应模型分析EHP-30域的最小二乘(LS)均值变化和相对于基线的总分(关键).关键试验治疗组报告了长达104周的结果,重点是relugolixCT组(即,relugolixCT或安慰剂24周,或延迟relugolixCT[relugolix40mg单药治疗12周,随后进行relugolixCT12周])。此外,评估痛经变化与NMPP和EHP-30评分变化之间的关系.
结果:在接受relugolixCT治疗的277名妇女中,LS平均EHP-30疼痛域评分提高了57.8%(LS平均变化:-32.8;95%CI:-35.5,-30.1),在第24、52和104周,分别为66.4%(LS平均变化:-37.7;95%CI:-40.3,-35.0)和72.2%(LS平均变化:-41.3;95%CI:-43.9,-38.7)。在EHP-30疼痛领域有临床意义改善的女性比例为75.9%,在第24、52和104周分别为83.6%和88.6%。非疼痛EHP-30领域和总分同样改善。观察到痛经/NMPP的变化与所有EHP-30域评分之间呈正相关。延迟relugolixCT和安慰剂→relugolixCT组的结果相似。
结论:使用relugolixCT观察到的子宫内膜异位症相关疼痛持续减少长达104周,伴随着功能和健康相关QoL的改善。这些发现补充了关键的SPIRIT试验的结果,显示relugolix联合治疗可显着减少痛经,非月经性盆腔疼痛(NMPP)和性交困难与安慰剂在绝经前妇女子宫内膜异位症相关疼痛中的比较。
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 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 as well as nonmenstrual pelvic pain (NMPP).
METHODS: Long-term extension study of the SPIRIT phase 3 trials.
METHODS: Clinics and University Hospitals.
METHODS: Premenopausal women with moderate-to-severe endometriosis pain who previously completed the randomized SPIRIT trials were eligible to enroll in an 80-week long-term extension where all women received relugolix CT.
METHODS: Relugolix CT (
relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg).
METHODS: Least squares (LS) mean changes in the EHP-30 domain and total scores from baseline (pivotal) were analyzed using a mixed-effects model. Results up to 104 weeks are reported by a pivotal trial treatment group with a focus on the relugolix CT group (i.e.,
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 as well as 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 in 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 that relugolix combination therapy significantly reduced dysmenorrhea, NMPP, and dyspareunia vs. placebo in premenopausal women with endometriosis-associated pain.
BACKGROUND: Registration/clinicaltrials.gov identifier: SPIRIT Extension Study (NCT03654274).