Bone mineral density after two years of treatment with relugolix combination therapy and one-year post-treatment follow-up in women with endometriosis: spirit program.

To evaluate bone mineral density (BMD) changes in women with endometriosis (EM)-associated pain treated with relugolix combination therapy (Rel-CT: relugolix 40 mg, estradiol 1 mg and norethindrone acetate 0.5 mg) in the SPIRIT long-term extension (LTE) study through 104 weeks and post-treatment follow-up (PTFU) for 12 months. In the pivotal SPIRIT 1 and 2 studies, premenopausal women (aged 18–50 years) with moderate-to-severe EM-associated pain were randomized 1:1:1 to receive once-daily Rel-CT, placebo or delayed Rel-CT (relugolix 40 mg monotherapy followed by Rel-CT, 12 weeks each) for 24 weeks. Women who completed SPIRIT 1 or 2 could enroll in the 80-week SPIRIT LTE and receive open-label Rel-CT up to 104 weeks. The study was amended at Week 104 to include PTFU at Month 6 (M6) and 12 (M12) after treatment cessation in all women, regardless of whether they met protocol-specified BMD loss criteria compared with pivotal study baseline. Least squares (LS) mean percent change from pivotal study baseline to Week 104 and M6 and M12 PTFU were summarized on the Week 104 completers using a mixed-effects model to account for patient attrition during the PTFU period. Mean percent changes were derived using last-observation-carried-forward (LOCF) to assess robustness of the model-based analysis. In SPIRIT 1 and 2, 1261 women were randomized and 1041 completed Week 24 of treatment. Of 802 (77%) women who entered the SPIRIT LTE, 501 (62%) women completed Week 104 of treatment. In the LTE safety population at lumbar spine, a small but not clinically meaningful BMD decline (<1%) was observed in women receiving Rel-CT at Week 12 that subsequently plateaued starting at Week 36 and was sustained for the duration of treatment of 104 weeks. For women treated with Rel-CT who completed 104 weeks of treatment (n=172), there were 43 and 55 women who had PTFU performed at M6 and M12, respectively. LS mean percent changes in BMD from baseline at Week 104, M6 and M12 PTFU at the lumbar spine were -0.41% (95% CI: –1.07, 0.26), 0.30% (95% CI: –0.52, 1.13) and 0.55% (95% CI: –0.25, 1.35), respectively. When analyzed by LOCF, mean percent changes from baseline at the lumbar spine were –0.18% (95% CI: –0.77, 0.41), –0.03% (95% CI: –0.58, 0.52) and 0.01% (95% CI: –0.54, 0.55), respectively. In women with EM-associated pain treated with Rel-CT whose changes in BMD were evaluated after treatment cessation, there was evidence of recovery, regardless of whether they maintained or lost BMD after two years of treatment.