Linzagolix benefits Hb levels, mood, QoL

The use of the oral GnRH antagonist linzagolix in patients with heavy menstrual bleeding (HMB) due to uterine fibroids induced multiple benefits including improved haemoglobin (Hb) levels, health-related quality of life (HRQoL), and mood, analysis of the PRIMROSE 1 and 2 trials showed.

Study participants were individuals with HMB due to uterine fibroids who were enrolled in the phase III, double-blind PRIMROSE 1 and 2 trials. They were randomized to receive linzagolix at 100 or 200 mg QD, with or without hormonal add-back therapy (ABT), or placebo for 52 weeks. Patients who received placebo in PRIMROSE 2 were switched to linzagolix 200 mg+ABT after week 24. Response to treatment was defined as ≥2 g/dL increase from baseline. Iron supplementation was provided for patients with severe anaemia (Hb level <10 g/dL) until their Hb levels exceeded 12 g/dL.

Improved Hb levels

A total of 165 patients in PRIMROSE 1 had severe anaemia, as did 93 patients in PRIMROSE 2. At 24 weeks, response to treatment occurred in 57.9, 61.5, 82.1, and 65.2 percent of patients who received linzagolix 100 mg, 100 mg+ABT, 200 mg, and 200 mg+ABT, respectively, in PRIMROSE 1, compared with 50 percent of those who received placebo. The respective percentages in PRIMROSE 2 were 62.5, 75, 60, and 73.7 percent, respectively, vs 46.2 percent with placebo. [ACOG 2022, abstract A105]

However, due to the small number of patients, statistical significance was not established, commented the authors.

The responses were maintained at week 52 in both trials. In PRIMROSE 1, 69.2, 62.5, 81.3, 75, and 40 percent of patients in the linzagolix 100 mg, 100 mg+ABT, 200 mg, 200 mg+ABT, and placebo groups, respectively, were responders. In PRIMROSE 2, 66.7, 100, 80, and 87 percent of linzagolix 100 mg, 100 mg+ABT, 200 mg, 200 mg+ABT recipients, respectively, were responders.

“High and low doses of linzagolix improved Hb levels in patients with uterine fibroids suffering from severe anaemia,” the authors noted.

Better mood, QoL

Linzagolix use also appeared to have a positive impact on mood disorders in this trial.

“[T]he incidence … of depression and other mood disorders, previously reported up to 24 weeks, was low and revealed no consistent drug-related pattern,” the authors said.

The follow-up for outcomes between weeks 24 and 52, based on analysis of 336 and 421 patients in PRIMROSE 1 and 2, respectively, seemed to echo the previous findings. [ACOG 2022, abstract A106]

One patient (1.1 percent) in PRIMROSE 2 experienced mood swings and one patient (1.1 percent) in PRIMROSE 1 experienced anxiety, both of whom were in the placebo/200 mg+ABT group. One patient in the 200 mg/200 mg+ABT group in PRIMROSE 2 experienced depression.

“There were no reports of suicidal ideation, affect lability, or altered mood,” the authors said.

A total of 1,012 patients pooled from the two trials were included in the HRQoL assessment which was carried out using the 3-month recall version of the Uterine Fibroid Symptom Health-Related Quality of Life (UFS QOL) questionnaire. [ACOG 2022, abstract A107]

The estimated mean change from baseline in HRQoL total score was 21.8, 28.2, 32.1, 31.5, and 12.7 in the 100 mg, 100 mg+ABT, 200 mg, 200 mg+ABT, and placebo groups, respectively (p<0.001 for all vs placebo). The HRQoL benefits persisted at 52 weeks.

At week 64, HRQoL declined for all treatment groups but did not reach baseline levels, ranging from a mean 12.83 to 19.45 in the linzagolix groups.

“Linzagolix treatment had substantial beneficial effects on HRQoL in women with uterine fibroids. The benefits persisted, with improvements not fully returning to baseline 12 weeks after treatment termination,” the authors pointed out.