Relugolix combo therapy could reduce HMB-related anaemia, distress

Relugolix combination therapy (relugolix-CT) comprising relugolix and estradiol (E2)/norethindrone acetate (NETA) could improve anaemia in women with heavy menstrual bleeding (HMB) due to uterine fibroids, according to pooled results of the phase III LIBERTY* 1 and 2 trials presented at ESHRE 2020.

“In women with uterine fibroids and anaemia at baseline, relugolix-CT, an oral gonadotropin-releasing hormone with estradiol/norethindrone, significantly improved haemoglobin concentrations at week 24,” said the researchers.

Study participants were premenopausal women aged 18–50 years with HMB (monthly blood loss [MBL] ≥80 mL per cycle) due to ultrasound-confirmed uterine fibroids. They were randomized 1:1:1 to receive oral relugolix-CT (relugolix: 40 mg/day; E2: 1.0 mg/day; NETA: 0.5 mg/day) for 24 weeks, delayed relugolix-CT (relugolix 40 mg/day only for 12 weeks followed by relugolix-CT for 12 weeks), or placebo for 24 weeks.

The present analysis comprises the 256 participants (mean age 42 years) who also had anaemia (baseline haemoglobin ≥8 and ≤10.5 g/dL; mean 9.5 g/dL). Mean MBL volume at baseline was 285.5 mL.

At 24 weeks, improvement in anaemia, marked by a haemoglobin increase of >2 g/dL from baseline, occurred in more relugolix-CT (pooled population) than placebo recipients (55.7 percent vs 11.7 percent; p<0.0001). [ESHRE 2020, abstract O-023]

Mean percentage increase in haemoglobin concentration from baseline was also greater in relugolix-CT compared with placebo recipients (23.0 percent vs 6.4 percent; p<0.0001). The greater increase in haemoglobin levels with relugolix-CT vs placebo was evident from week 4 of treatment.

“[T]hese significant improvements in haemoglobin concentrations from baseline with relugolix-CT treatment relative to placebo reflect the impact that HMB had on study participants and how reductions in MBL volume translate into clinically meaningful improvements in haemoglobin levels in patients with uterine fibroids,” the researchers said.

Adverse event incidence was generally comparable between relugolix-CT and placebo recipients.

The researchers noted that patients with iron deficiency anaemia also received iron supplementation during the trial, though the treatment was not standardized. They acknowledged that patient adherence to supplementation and route of administration (oral vs parenteral) may have influenced the findings. 

Reduced patient-reported distress

A separate analysis of the pooled LIBERTY 1 and 2 trials showed that at week 24, relugolix-CT resulted in greater improvement from baseline in several patient-reported distress outcomes.

There was a significantly greater reduction in distress due to HMB, passing of blood clots, and pelvic pressure/tightness from baseline to 24 weeks, as measured using the Bleeding and Pelvic Discomfort (BPD) scale, in relugolix-CT** compared with placebo recipients (difference, 31; p<0.0001). [ESHRE 2020, abstract O-024]

Relugolix-CT recipients also experienced a greater improvement in the Revised Activities (RA) scale, which assessed five aspects of physical and social activities, compared with placebo recipients (difference, 29.3; p<0.0001).

More relugolix-CT than placebo recipients experienced a clinically meaningful treatment response, defined as a ≥20-point difference between baseline and 24 weeks (62.5 percent vs 28.1 percent [BPD scale] and 61.7 percent vs 34.0 percent [RA scale]; p<0.0001 for both).

“Relugolix-CT not only reduced HMB in women with uterine fibroids, but also improved patient-reported outcomes, by reducing the distress caused by frequent … symptoms and improving daily activities,” said the researchers. These outcomes can be easily interpreted and communicated to patients, they added.