Fezolinetant superior to other non-HTs at reducing bothersome VMS due to menopause

Treatment with fezolinetant 45 mg outperforms other nonhormone therapies (non-HTs) in terms of minimizing the frequency of moderate-to-severe vasomotor symptoms (VMS) in women undergoing menopause, according to a study from the US.

Meanwhile, some HT regimens that have greater efficacy than fezolinetant are not available in the US.

For the study, researchers conducted a systematic review and Bayesian network meta-analysis to compare the efficacy of fezolinetant 45 mg with those of HT and non-HT for VMS in postmenopausal women.

Multiple online databases were searched for phase III or IV randomized controlled trials in postmenopausal women with ≥7 moderate-to-severe VMS per day or ≥50 VMS per week. Outcomes such as the mean change in frequency and severity of moderate-to-severe VMS from baseline to week 12 and the proportion of women with a ≥75-percent reduction in VMS frequency at week 12 were evaluated using fixed-effect models.

The network meta-analysis included data from the pooled phase III fezolinetant trials and 23 comparator publications. A total of 19 studies reported on the frequency of VMS (34 regimens), six studies reported on the severity of VMS (seven regimens), and nine studies reported on the ≥75-percent response rate (15 regimens).

Changes in VMS frequency were not significantly different between fezolinetant 45 mg and any of the 27 HT regimens. However, fezolinetant 45 mg produced a significant reduction in the frequency of moderate-to-severe VMS events per day compared with the all non-HTs assessed—paroxetine 7.5 mg (mean difference, 1.66, 95 percent credible interval [CrI], 0.63–2.71), desvenlafaxine 50 to 200 mg (mean differences, from 1.12, 95 percent CrI, 0.10–2.13 to 2.16, 95 percent CrI, 0.90–3.40), and gabapentin extended-release 1,800 mg (mean difference, 1.63, 95 percent CrI, 0.48–2.81)—and placebo (mean difference, 2.78, 95 percent CrI, 1.93–3.62).

In terms of VMS severity, the HT tibolone 2.5 mg had superior efficacy than fezolinetant 45 mg, but fezolinetant 45 mg had significantly greater efficacy compared with desvenlafaxine 50 mg and placebo.

For ≥75-percent responder rates, fezolinetant 45 mg was less efficacious than tibolone 2.5 mg (not available in the US) and conjugated oestrogens 0.625 mg/bazedoxifene 20 mg (available only as 0.45 mg/20 mg in the US), had comparable efficacy as other non-HT regimens studied, and was superior to desvenlafaxine 50 mg and placebo.