Integrated long-term bone mineral density outcomes in women receiving relugolix combination therapy in liberty and spirit studies vs non-treated women

Relugolix combination therapy (Rel-CT [once-daily relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg]) is being developed to treat heavy menstrual bleeding associated with uterine fibroids (UF), and endometriosis-associated pain (EM). In the Phase 3 LIBERTY 1/2 trials and long-term extension (LTE) study for UF, Rel-CT maintained BMD through 52 weeks. In the SPIRIT 1/2 trials and LTE study for EM, Rel-CT minimized BMD loss through 24 weeks, after which BMD plateaued up to 52 weeks. Since the mean age of women in the UF studies was higher than that in the EM studies, a pooled population assessment was undertaken to determine if a single BMD profile with a full range of ages could be developed for Rel-CT. A 52-week observational study in a group of contemporaneous age-matched women with UF or EM (Natural History Study [NHS], N=714) was used to benchmark BMD data from the pivotal and LTE studies. Percent change in BMD from baseline with 95% CI was summarized by treatment group and anatomical location using descriptive statistics: mean, 95% CI (Table). There were 2019 women included in pooled data from the 24-week LIBERTY and SPIRIT studies and associated 28-week LTE studies. Percent change from baseline in pooled BMD was consistent with trends in the separate UF and EM populations. Specifically, at the lumbar spine at Week 12, there was a –0.56% change in BMD with Rel-CT that was not clinically significant and likely reflected adjustment from endogenous to exogenous estradiol in the context of Rel-CT. This timepoint marked the beginning of a plateau. At Week 52, the change from baseline was –0.66% in women treated with Rel-CT compared with 0.19% in women in the NHS (Table). Women initially treated with relugolix monotherapy experienced a larger change in BMD from baseline to Week 12 (–1.84%) that plateaued after transition to Rel-CT with change from baseline to Week 52 of –1.31%.TablePercent change from baseline in lumbar spine BMDNHS (mean, 95% CI)N=714Pooled SPIRIT and LIBERTYRel-CT (mean, 95% CI)N=672Delayed Rel-CT* (mean, 95% CI)N=675Week 12––0.56% (–0.76, –0.36)–1.84% (–2.03, –1.64)Week 240.26% (0.07, 0.44)–0.57% (–0.78, –0.36)–2.00% (–2.23, –1.77)Week 36––0.61% (–0.88, –0.34)–1.67% (–1.94, –1.40)Week 520.19% (–0.04, 0.42)–0.66% (–0.97, –0.35)–1.31% (–1.62, –1.01)*Relugolix monotherapy for 12 weeks then Rel-CT for 40 weeks. Open table in a new tab *Relugolix monotherapy for 12 weeks then Rel-CT for 40 weeks. In premenopausal women with UF or EM, treatment with Rel-CT lead to an initial insignificant decline in BMD followed by a plateau through the 52 weeks of the study.