O-032 Effect of relugolix combination therapy in women with endometriosis-associated pain who received prior first-line hormonal treatment: SPIRIT 1 and 2

Abstract

Abstract Study question To assess the effect of oral relugolix combination therapy (Relugolix-CT) in the subgroup of women with endometriosis-associated pain who received prior first-line hormonal treatment. Summary answer Relugolix-CT significantly reduced dysmenorrhoea and non-menstrual pelvic pain (NMPP) through 24 weeks in women with endometriosis-associated pain who received prior first-line hormonal treatment. What is known already ESHRE recommends hormonal contraceptives or progestogens as first-line therapy for endometriosis; however, these treatments may not be efficacious for all women. SPIRIT 1&2 were Phase 3, replicate, randomised studies of oral Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0.5 mg) in premenopausal women (aged 18–50 years) with moderate-to-severe endometriosis-associated pain. In SPIRIT 1&2, Relugolix-CT significantly improved dysmenorrhoea, NMPP and daily functioning (measured by the Endometriosis Health Profile-30 pain domain score) compared with placebo over 24 weeks. Relugolix-CT was well-tolerated and bone mineral density showed a minimal decline (<1%) from baseline to Week 24. Study design, size, duration At screening, women were required to have at least moderate menstrual and non-menstrual pain during their last cycle. In total, 1261 women with diagnosed endometriosis and moderate-to-severe dysmenorrhoea and NMPP at baseline were randomised 1:1:1 to receive once-daily Relugolix-CT or placebo for 24 weeks, or delayed Relugolix-CT (relugolix 40 mg then Relugolix-CT; 12 weeks each). Study candidates who received hormonal treatment for endometriosis completed a washout period prior to the screening and run-in period. Participants/materials, setting, methods Analyses were performed using pooled SPIRIT 1&2 data in women previously receiving first-line hormonal treatment (e.g. oral contraceptives and/or progestogens; N = 392). Co-primary endpoints: proportion of dysmenorrhoea and NMPP responders at Week 24. Responders were women achieving a predefined, clinically meaningful reduction from baseline in daily Numerical Rating Scale (NRS [0=no pain, 10=worst pain imaginable]) score and no increase in analgesic use. Least squares (LS) mean changes in NRS scores were assessed by a mixed-effects model. Main results and the role of chance In total, 121 women in the Relugolix-CT group and 134 in the placebo group had received prior first-line hormonal treatment, of which combined oral contraceptives and/or dienogest were the most common medications. Data for the delayed Relugolix-CT group were used for safety assessment only and are not reported here. Baseline demographics and clinical characteristics were comparable between the subgroup of women who received prior first-line hormonal treatment and the overall study population. In this subgroup, the proportion of dysmenorrhoea responders with Relugolix-CT vs placebo at Week 24 was 70.2% vs 27.6%, respectively (p < 0.0001); the proportion of NMPP responders was 60.3% vs 40.3%, respectively (p = 0.0013). In the Relugolix-CT group, LS mean NRS scores for dysmenorrhoea decreased from 7.2 (severe) at baseline to 1.7 (mild) at Week 24, with a significant change from baseline vs placebo (p < 0.0001). LS mean NRS scores for NMPP decreased from 5.6 (moderate) at baseline to 2.8 (mild) at Week 24 with Relugolix-CT, with a significant change from baseline vs placebo (p = 0.0097). The proportion of women who were analgesic-free at baseline was 7.4% with Relugolix-CT and 3.7% with placebo; this increased to 48.8% with Relugolix-CT and 18.7% with placebo at Week 24 (p < 0.0001). Limitations, reasons for caution Assessment of endometriosis-associated pain at screening visit was done after the wash-out period; therefore, data for endometriosis symptoms experienced by women while receiving hormonal treatment prior to study entry, as well as the duration of the previous treatments, were not available. Wider implications of the findings Relugolix-CT significantly reduced dysmenorrhoea and NMPP, vs placebo, through 24 weeks in women with endometriosis-associated pain who received prior first-line hormonal treatment. The proportion of women in this subgroup who were analgesic-free increased through 24 weeks with Relugolix-CT. Results were comparable to the overall SPIRIT 1&2 population. Trial registration number NCT03204318; NCT03204331