Achieving Minimal-to-No Pain in Women with Endometriosis Treated with Relugolix Combination Therapy: SPIRIT Extension Trial

Andrea S Lukes,1 Roberta Venturella,2 Krzysztof Dynowski,3 Rachel B Wagman,4 Julie S Perry,4 Yi Zhong,5 Viatcheslav G Rakov,6 Sylvia Mechsner,7 Neil P Johnson81Carolina Woman’s Research and Wellness Center, Durham, NC, USA; 2Department of Clinical and Experimental Medicine, Unit of Obstetrics and Gynecology, Magna Graecia University of Catanzaro, Catanzaro, Italy; 3Department of Obstetrics & Gynaecology, The Medical Centre of Postgraduate Education, Warsaw, Poland; 4Clinical Research, Sumitomo Pharma America, Inc., Marlborough, MA, USA; 5Biostatistics, Sumitomo Pharma America, Marlborough, MA, USA; 6Research and Development, Sumitomo Pharma Switzerland GmbH, Basel, Switzerland; 7Clinic for Gynecology, Endometriosis Center Charité, Charité-Universitätsmedizin Berlin, Berlin, Germany; 8Obstetrics and Gynaecology, Flinders University, Adelaide, SA, AustraliaCorrespondence: Andrea S Lukes, Carolina Woman’s Research and Wellness Center, Durham, NC, USA, Email [email protected]: Relugolix is an oral, non-peptide gonadotropin-releasing hormone receptor antagonist administered as once-daily combination therapy (relugolix-CT; 40 mg relugolix, 1 mg estradiol, 0.5 mg norethindrone acetate) to reduce endometriosis symptoms while potentially minimizing hypoestrogenic effects. In the 24-week SPIRIT1& 2 studies, relugolix-CT significantly improved endometriosis-associated pain versus placebo, with improvements sustained over the 80-week open-label Long-Term Extension (LTE; all received relugolix-CT). This post hoc analysis of SPIRIT1, 2 and LTE data assessed temporal effects of relugolix-CT on minimal-to-no pain, amenorrhea, and analgesic-free status.Patients and Methods: This analysis included women who received relugolix-CT, delayed relugolix-CT, or placebo in SPIRIT 1 or 2 and entered the LTE. Cumulative probability and median time to minimal-to-no pain for dysmenorrhea and non-menstrual pelvic pain (NMPP), amenorrhea, and analgesic-free status were assessed.Results: In SPIRIT1& 2, 802/1261 women entered the LTE; 501/802 completed 104-week treatment. Median time to minimal-to-no pain for dysmenorrhea was 8 weeks for relugolix-CT and delayed relugolix-CT and was not reached with placebo within 24 weeks; cumulative probability of minimal-to-no dysmenorrhea at Week 24 was 82.5%, 86.4%, and 22.4%, respectively, increasing to 95.3%, 95.9%, and 94.9% at Week 104. Amenorrhea paralleled dysmenorrhea. Median time to minimal-to-no NMPP was 32, 28, and 40 weeks in the relugolix-CT, delayed relugolix-CT, and placebo groups, respectively; cumulative probability of minimal-to-no NMPP was 42.6%, 42.2%, and 28.9% at Week 24, increasing to 70.5%, 74.7%, and 74.3% at Week 104. In the relugolix-CT group, median time to analgesic-free status was 16 weeks; 68.8% and 94.9% were analgesic-free at Weeks 24 and 104. Delayed relugolix-CT results were similar. Analgesic-free status improved in the placebo group after relugolix-CT initiation.Conclusion: In this post hoc analysis, women receiving relugolix-CT for up to 104 weeks had rapid dysmenorrhea improvement with amenorrhea and reduced analgesic use, with longer treatment associated with further NMPP reduction.Keywords: GnRH receptor antagonist, dysmenorrhea, amenorrhea, non-menstrual pelvic pain, analgesic-free, opioid-free