Fezolinetant Compared With Placebo for Vasomotor Symptoms in Menopause: A Systematic Review and Meta-Analysis [ID 2683665

Abstract

INTRODUCTION: Although menopausal hormone therapy is the most effective choice for vasomotor symptoms (VMS), it is not appropriate for everyone. Therefore, fezolinetant, a nonhormonal, selective neurokinin 3 receptor antagonist has been proposed as an alternative therapy. We aimed to perform a meta-analysis of the clinical outcomes comparing fezolinetant and placebo for vasomotor symptoms in menopause. METHODS: PubMed, Embase, and Cochrane databases were searched for studies comparing 30 mg of fezolinetant with placebo in menopausal women. Outcomes assessed were frequency of moderate/severe VMS and change from baseline to week 12 in total VMS score. Our secondary outcomes were headache, bone fracture, and treatment-emergent adverse events (TEAEs) leading to discontinuation of the drug and TEAEs leading to death. We only included randomize control trials. Statistical analysis was performed using RevMan 5.4.1. Heterogeneity was assessed with I2 statistics and random-risk effect was used if 𝐼2>50%. RESULTS: Seven studies met inclusion criteria, with 3,678 patients included, of whom 1,067 were randomized to fenzolinetant. No statistical difference was found in frequency of moderate/severe VMS or TEAEs leading to death, TEAEs leading to drug discontinuation. However, severity of moderate and severe VMS comparing to baseline VMS (MPR) was significantly lower with fezolinetant 30 mg BID (odds ratio [OR] −0.22; 95% CI, −0.30, −0.13; P=.00001; I 2=89%). In addition, headache and bone fractures (OR −6.98; 95% CI, −6.98 to −6.73; P=.03; I 2=100%) were lower with fezolinetant compared to placebo. CONCLUSION: Our findings suggest that 30 mg of fezolinetant is a well-tolerated nonhormone therapy that improves vasomotor symptoms with menopause. The safety and efficacy demonstrated in our study support the potential use of fezolinetant as an effective nonhormonal treatment option and may reduce bone fractures and headaches in menopausal women.