Comment: The certainty of the evidence is downgraded by indirectness (only short-term outcomes reported) and by imprecise results (few patients in most studies).
A analysis of pooled data 1 from SKYLIGHT 1 and SKYLIGHT 2 RCTs included 1022 women aged ≥40 to ≤65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS. Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg). Fezolinetant 45 mg mean reduction over placebo in Menopause-Specific Quality of Life (MENQoL) total score was -0.57 (95% CI -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and Patient Global Impression of Change in VMS (WPAI-VMS) scores improved.
A systematic review and meta-analysis 2 included 6 RCTs involving 3301 patients. Compared to placebo, fezolinetant reduced the frequency of VMS episodes from baseline (SMD = -0.64, 95 % CI -0.77 to -0.5) and (SMD -0.63, 95 % CI -0.72 to -0.53] at weeks 4 and 12 respectively. Additionally, fezolinetant reduced VMS severity score (SMD -0.59, 95 %CI -0.77 to -0.42) and (SMD = -0.4, 95 % CI [-0.54, -0.27]) at weeks 4 at 12 respectively. These reductions were positively reflected on Menopause specific quality of life score (SMD -0.46, 95 %CI -57 to -0.34), (SMD -0.37, 95 %CI -0.48 to -0.25) at weeks 4 and 12 respectively. Regarding safety analysis, fezolinetant showed increased risk for drug-related TEAEs (RR = 1.47, 95 %CI [1.06,2.04]), treatment-emergent serious adverse effects (RR 1.67, 95 %CI 1.09 to 2.55), fatigue (RR 4.05, 95 %CI 1.27 to 12.88), arthralgia (RR 2.83, 95 %CI 1.02 to 7.8) and ALT or AST > 3 times (RR = 2, 95 %CI 1.12 to 3.57), with no other statistically significant difference regarding other safety terms.
A meta-analysis 3 included a total of 2168 participants from 5 RCTs. Fezolinetant significantly lowered VMS frequency, with pooled mean difference of 2.62 (95% CI 1.84 to 3.41). The pooled mean difference for fezolinetant compared with placebo for the MENQOL (Menopause-Specific Quality of Life) measure was -0.60 (95% CI, -0.92 to -0.28), and the mean percentage improvement in VMS frequency was 22.51% (95% CI, 15.35 to 29.67). Fezolinetant was associated with improvement in sleep quality when compared with placebo.
Date of latest search: 2024-09-28
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