Pain Relief With Linzagolix in UFs: PRIMROSE Trials

TOPLINE:In women with uterine fibroids (UFs), pain relief with linzagolix was largely driven by a reduction in heavy menstrual bleeding (HMB), with a smaller contribution from a reduction in fibroid volume (FV). Hormonal add-back therapy (ABT) also affected these effects.

METHODOLOGY:Researchers conducted a post hoc mediation analysis of pooled data from two double-blind placebo-controlled phase 3 trials (PRIMROSE 1 and 2) that included women aged 18 years or older with ultrasound-confirmed UFs and HMB.A total of 1012 participants (mean age, 42.3 years; 64% White; mean body mass index, 29.8; median total FV at baseline, 53 cm3) were enrolled in the analysis; 75% of them reported moderate to severe pain and 43% reported severe pain at baseline.Participants were randomly assigned to receive either linzagolix (100 mg and 200 mg, with and without hormonal ABT consisting of 1 mg oestradiol and 0.5 mg norethisterone acetate taken once a day) or placebo.The analysis focused on a clinically significant reduction in pain, defined as a change in two or more pain categories from baseline to week 24, assessed using the Numeric Rating Scale; HMB was assessed using the alkaline haematin method, and the FV was assessed using ultrasound.The primary outcome was the reduction in pain, mediated by reductions in HMB and FV.TAKEAWAY:The reduction in HMB explained between 28% and 51% of the effect of linzagolix on pain reduction across treatment arms, with odds ratios [ORs] ranging from 1.45 for 100 mg without ABT to 2.43 for 200 mg with ABT).The reduction in pain of 18.8%-30.9% vs 6.8% was achieved with linzagolix vs placebo.The reduction in FV accounted for 2%-8% of the treatment effect, with statistical significance noted only in the 200 mg without ABT arm (OR, 1.19; P = .002).The ORs for the total treatment effect on pain reduction ranged from 3.83 for 100 mg without ABT to 8.37 for 200 mg without ABT (P < .001).The residual treatment effect, not explained by a reduction in HMB or FV, varied from 44% to 67% across treatment arms, reaching statistical significance only in the 200 mg without ABT arm (P = .002).IN PRACTICE:"This analysis showed that reductions in pain were significantly mediated by reductions in HMB (all doses) and FV (200 mg alone) in linzagolix-treated women with UFs. Further research is needed to identify additional mediating factors," the authors of the study wrote. SOURCE:This study was led by Sven Becker, Department of Gynecology and Obstetrics, University Hospital Frankfurt, Frankfurt, Germany. It was published online on May 06, 2025, in BJOG: An International Journal of Obstetrics & Gynaecology. LIMITATIONS:This study could not explain all proportions of pain reduction, suggesting the need to explore other contributing factors. Pooling data from two trials might introduce bias, despite adjustments for factors like race and age. Pain was assessed globally as perceived by patients rather than by symptom type/location, which may have obscured the role of different pain types in the observed outcomes. DISCLOSURES:The PRIMROSE 1 and PRIMROSE 2 trials were funded by ObsEva. The current analysis was funded by Theramex. Several authors reported being employees and receiving honoraria from the funding agency and from various other sources. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.