Subgroup findings boost elagolix benefit in uterine fibroid-induced menstrual bleeding

The addition of the oral GnRH* antagonist elagolix to hormonal add-back therapy (E2/NETA**) reduces menstrual blood loss (MBL) in women with heavy menstrual bleeding (HMB) associated with uterine fibroids (UF) and comorbid adenomyosis, with the extension phase showing benefits beyond 6 months, according to data presented at ACOG 2020.

Data were pooled from two investigational phase III studies – Elaris UF-1 and UF-2 – evaluating premenopausal women aged 18–51 years (n=790) with HMB (>80 mL MBL/cycle) tied to UF and baseline adenomyosis diagnosed by ultrasound and/or MRI. Women were randomized to receive elagolix BID 300 mg alone or with add-back therapy (E2 1 mg/NETA 0.5 mg), or placebo for 6 months.

UF + adenomyosis

Of the 126 participants who had adenomyosis at baseline, the fraction of women achieving the primary endpoint was significantly greater in the elagolix + E2/NETA vs the placebo arm (76.8 percent vs 12.1 percent; p<0.001). [ACOG 2020, abstract 15B]

Responder rate was also more significant with elagolix + E2/NETA vs placebo for the secondary endpoints of amenorrhoea and suppression of bleeding (p<0.001).

“[These findings show that more women in this subset achieved] <80 mL MBL during the final month and ≥50 percent reduction in MBL from baseline to final month,” said the researchers. “These results … were consistent with the all-subject group … suggesting that elagolix is effective in reducing HMB in women with UF despite the presence of adenomyosis,” they added.

Various subgroups

Across all subgroups, statistically significant differences were observed in favour of elagolix + E2/NETA over placebo in terms of the primary endpoint (72.2 percent vs 9.3 percent; p<0.001), mean change in MBL (–172.5 mL vs –0.8 mL; p<0.001), and the fraction of women who achieved amenorrhea (50.4 percent vs 4.5 percent; p<0.001). [ACOG 2020, abstract 23B]

“[These findings show that] elagolix with add-back therapy was effective in reducing HMB associated with UF regardless of age, body mass index, ethnicity, race, fibroid location based on FIGO*** classification, uterine and primary fibroid volume, and pregnancy history,” said the researchers.

Extension results

In the extension study, Elaris UF-EXTEND, elagolix recipients in Elaris UF-1 and UF-2 who completed the initial treatment period (n=433) were instructed to continue their regimen for an additional 6 months (up to 12 months). [ACOG 2020, abstract OP04-5D]

A drop in baseline MBL (mean, 224.7 mL) was observed with elagolix + E2/NETA as early as the first month of the extension period (mean, –186.5 mL), which was sustained through the sixth month (mean, –221.4 mL).

At the end of the 6-month extension period, nearly three-quarters (74.8 percent) had suppression of bleeding (ie, no bleeding; spotting allowed). About 72 percent of women with a baseline haemoglobin level of ≤10.5g/dL had a haemoglobin increase of >2 g/dL.

Of those who received up to 12 months of elagolix + E2/NETA, 87.9 percent met the primary endpoint. “[This finding implies that] up to 12 months of elagolix + E2/NETA provided sustained MBL reduction in women with UF,” said the researchers.

These subgroup and extension results add data to the initial findings of Elaris UF-1 and UF-2, thus boosting the therapeutic potential of elagolix in this patient subgroup. [N Engl J Med 2020; 382:328-340]