O-131 The effect of time since surgical diagnosis of endometriosis on treatment outcomes with relugolix combination therapy in women with endometriosis-associated pain: SPIRIT program

Study question To assess the efficacy of Relugolix-CT vs placebo in women who were surgically diagnosed with endometriosis <5 and > = 5 years ago. Summary answer Treatment outcomes did not differ for dysmenorrhea and daily functioning between subgroups of patients with <5 years or ≥ 5 years since surgical diagnosis. What is known already Time since clinical manifestation and diagnosis of endometriosis may influence the treatment success of patients with endometriosis-associated pain. SPIRIT 1 and 2 were randomized, double-blind, placebo-controlled Phase 3 studies of Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) in premenopausal women (age 18–50 years) with surgically diagnosed endometriosis and a history of moderate-to-severe dysmenorrhea and non-menstrual pelvic pain (NMPP). These studies previously demonstrated that Relugolix-CT significantly reduced dysmenorrhea and NMPP, and improved daily functioning measured by the Endometriosis Health Profile-30 (EHP-30) pain domain score vs placebo over 24 weeks. Study design, size, duration Premenopausal women with surgically diagnosed endometriosis and moderate-to-severe dysmenorrhea and NMPP at baseline were randomized 1:1:1 to 24 weeks of treatment with once daily oral Relugolix-CT, delayed Relugolix-CT (relugolix 40 mg monotherapy for 12 weeks followed by Relugolix-CT for 12 weeks), or placebo. The proportion of dysmenorrhea and NMPP responders at Week 24/End-of-Treatment (EoT), based on daily Numerical Rating Scale (NRS), and analgesic use status were co-primary endpoints. Participants/materials, setting, methods Pooled SPIRIT 1 and 2 data of patients who received 24 weeks of treatment with once daily Relugolix-CT (N = 418) or placebo (N = 416) are presented. Outcomes for the delayed Relugolix-CT group were only for the safety assessment and therefore not reported here. Analyses of NRS scores for dysmenorrhea, NMPP, and EHP-30 pain domain score were carried out in the subgroups of patients with time since diagnosis of < 5 years (N = 579) and ≥5 years (N = 255). Main results and the role of chance Baseline demographics and clinical characteristics were comparable between the time since diagnosis subgroups except for a numerically higher mean age in the ≥5-years subgroup. Mean time since diagnosis (standard deviation) was 2.1 (1.5) years with both Relugolix-CT and placebo for <5-years subgroup, and 8.0 (2.8) and 7.8 (2.3) years, respectively, for ≥5-years subgroup. In Relugolix-CT-treated patients, mean NRS score for dysmenorrhea decreased from 7.5 (severe) to 1.8 (mild) in the <5-years subgroup and from 6.9 (moderate) to 1.8 (mild) in the ≥5-years subgroup with a significant difference to placebo (p < 0.0001, both subgroups), and demonstrating 74.8% and 72.7% reduction in pain from baseline to Week 24/EoT, respectively. Mean NRS score for NMPP decreased from 6.0 (moderate) to 3.0 (mild) with a significant difference compared with placebo (p < 0.0001), equating to 48.8% pain reduction in the <5-years subgroup, and from 5.6 (moderate) to 2.7 (mild) equating to 51.5% pain reduction (p = 0.089) in the ≥5-years subgroup. Improvement of daily functioning as measured by EHP-30 pain domain score was significantly greater with Relugolix-CT vs placebo in both subgroups, with decrease in EHP-30 pain score from 59.1 to 24.0 in the <5-years subgroup, and from 57.4 to 21.1 in the ≥5-years subgroup (p < 0.0001, both subgroups). Limitations, reasons for caution A lower number of patients were included into the subgroup with ≥5-years since surgically diagnosed endometriosis. Five-year dichotomy was close to the mean time since surgical diagnosis in the studies and to certain extent is arbitrary. Furthermore, time since surgical diagnosis is not the same as time since symptom onset. Wider implications of the findings In women with endometriosis-associated pain, Relugolix-CT vs placebo significantly reduced dysmenorrhea and improved daily functioning in both groups: with surgical diagnosis of < 5 years or ≥ 5 years. Substantial decrease in NMPP was also observed and was significantly different to placebo in the <5-years subgroup. Trial registration number NCT03204318 and NCT03204331