Sustained Efficacy and Safety of Relugolix Combination Therapy in Women with Endometriosis-Associated Pain: Spirit 52-Week Data

Abstract

<h3>Study Objective</h3> To evaluate long-term safety and efficacy of relugolix combination therapy (Relugolix-CT) to treat endometriosis-associated pain. <h3>Design</h3> SPIRIT Extension was a Phase 3, open-label, single-arm, 80-week study. <h3>Setting</h3> 170 clinical research centers globally. <h3>Patients or Participants</h3> Premenopausal women (age 18–50 years) with endometriosis, moderate-to-severe dysmenorrhea and non-menstrual pelvic pain (NMPP) at baseline who completed the 24-week pivotal studies (SPIRIT 1/2) and were eligible to participate were enrolled. <h3>Interventions</h3> Once-daily Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg). <h3>Measurements and Main Results</h3> Co-primary endpoints: proportion of dysmenorrhea/NMPP responders at Week 52, using Numerical Rating Scale (NRS) scores (0=no pain, 10=worst pain imaginable). Dysmenorrhea/NMPP responder: women who achieved a clinically meaningful reduction from baseline in NRS score (2.8/2.1, respectively) without increased analgesic use. Secondary endpoints: change in Endometriosis Health Profile-30 (EHP-30) pain domain scores, analgesic/opioid use. Safety endpoints: adverse events, bone mineral density (BMD) evaluation. Of 1,261 women randomized in SPIRIT 1/2, 802 enrolled in the extension; 681 completed 52 weeks of treatment. Data are reported for women who received Relugolix-CT through 52 weeks. The proportion of responders for dysmenorrhea was 84.8% and 73.3% for NMPP. NRS least squares (LS) mean scores for dysmenorrhea, NMPP and dyspareunia decreased from 7.4 (severe), 6.0 (moderate) and 5.9 (moderate) at pivotal baseline to 1.3 (mild), 2.2 (mild) and 2.4 (mild) at Week 52, equating to 82.8%, 62.9% and 60.1% reductions. Daily functioning (EHP-30 pain domain score) improved (–38.1 point); most women (85.6%) were opioid-free at Week 52. No disproportionate increase in adverse event incidence and no new safety signals were identified. Lumbar spine BMD was preserved, with LS mean change from baseline to Week 52 of –0.81% (95% CI: –1.26, –0.36). <h3>Conclusion</h3> Relugolix-CT was well tolerated and demonstrated sustained improvement of endometriosis-associated pain and maintenance of BMD through 52 weeks.