Relugolix-CT benefit for endometriosis-associated pain sustained through week 104

Long-term combination therapy with relugolix plus oestradiol and norethindrone (relugolix-CT) shows sustained reductions in dysmenorrhoea and non-menstrual pelvic pain (NMPP) for up to 2 years in premenopausal women with endometriosis, according to the SPIRIT extension* study presented at ESHRE 2022.

This 80-week long-term extension study included 802 premenopausal women (mean age 34 years) with endometriosis and moderate-to-severe dysmenorrhoea and NMPP who completed the 24-week pivotal SPIRIT 1 and 2 studies. Participants were initially randomized to receive once-daily relugolix-CT** (n=277), delayed relugolix-CT (relugolix 40 mg alone for 12 weeks, followed by relugolix-CT for 12 weeks; n=247), or placebo (n=275) for 24 weeks. After which, all participants received relugolix-CT only up to week 104. [ESHRE 2022, abstract O-305]

At week 104, more than 80 percent of women achieved a mean reduction in Numerical Rating Scale (NRS) score of ≥2.8 points for dysmenorrhoea and no increase of analgesic use (84.8, 83.0, and 80.4 percent in the relugolix-CT, delayed relugolix-CT, and placebo-relugolix-CT groups, respectively).

Similarly, 75.8, 71.7, and 73.1 percent of women in the respective relugolix-CT, delayed relugolix-CT, and placebo-relugolix-CT groups, respectively, achieved a mean reduction in NRS score of ≥2.1 points for NMPP and no increase of analgesic use at week 104.

These findings were consistent with the week-52 results that have been previously reported (84.8 percent [dysmenorrhoea] and 73.3 percent [NMPP]), thus reflecting the sustained reductions with relugolix combination therapy.

The reductions in NRS score for dyspareunia were consistent across all treatment groups at week 104 (least squares mean change from baseline, -3.5, -2.9, and -3.4 points in the relugolix-CT, delayed relugolix-CT, and placebo-relugolix-CT groups, respectively).

“[All treatment groups also showed] an improvement in daily activities and functioning as measured by the Endometriosis Health Profile-30 pain domain score,” said Dr Christian Becker from the University of Oxford, Oxford, UK.

A high percentage of patients remained analgesic-free (75.1 percent, 76.5 percent, and 76.0 percent for relugolix-CT, delayed relugolix-CT, placebo-relugolix-CT groups, respectively) and opioid-free at week 104 (91.0 percent, 88.3 percent, and 90.5 percent, respectively).

“Relugolix-CT was generally well tolerated and was associated with only a mean decrease of <1 percent in bone mineral density that did not progress during long-term treatment,” Becker noted.

“[Despite the open-label design and lack of control group, our findings show that] relugolix-CT once daily over 2 years in women with moderate-to-severe endometriosis-associated pain demonstrated a sustained reduction in dysmenorrhoea, NMPP, and dyspareunia,” said Becker.

“Relugolix-CT remains investigational for the treatment of endometriosis-associated pain,” he added.

*SPIRIT extension: Efficacy and safety extension study of relugolix in women with endometriosis-associated pain