Fezolinetant and vasomotor symptoms in menopause
Näytönastekatsaukset
22.9.2025
Level of evidence: B
Oral fezolinetant 45 mg, when compared to placebo is probably effective in reducing frequency of moderate to severe vasomotor symptoms in postmenopausal women.
Level of evidence is downgraded due to the risk of bias. In addition, suspected publication bias was detected (two industry funded studies).
Applicability of the evidence: good. Of note is, however, that patients with previous or current malign disease or any long-term disease were excluded from both trials. There were no significant differences is harms between the study groups.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| «Lederman S, Ottery FD, Cano A, ym. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet 2023;401(10»1 | RCT, multinational | Menopausal women, aged 40-65 years | Fezolinetant 45 mg and placebo | 1. Frequency of moderate-to-severe vasomotor symptoms 2. Severity of vasomotor symptoms | Moderate |
| «Johnson KA, Martin N, Nappi RE, ym. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. J Clin Endocrinol Metab 2023;108(8):1981-1997»2 | RCT, multinational | Same as study 1 | Same as study 1 |
RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis
| Reference | Comments |
|---|---|
| «Lederman S, Ottery FD, Cano A, ym. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet 2023;401(10»1 | The study included three arms (placebo, fezolinetant 30mg, and fezolinetant 45mg). In this current care evidence summary, we focus on fezolinetant 45 mg and placebo arms while only fezolinetant 45 mg is available in Finland. Inclusion criteria: women aged 40–65 years having an average of seven or more moderate-to-severe hot flashes per day before randomisation and seeking treatment or relief for vasomotor symptoms. All women had spontaneous amenorrhoea for at least 12 consecutive months, spontaneous amenorrhoea for at least 6 months with biochemical criteria of menopause (follicle stimulating hormone >40 IU/L), or bilateral oophorectomy for at least 6 weeks before the screening visit Exclucion criteria: Receiving strong or moderate cytochrome P450 1A2 inhibitors, hormone replacement therapy, hormonal contraceptive, or any treatment for vasomotor symptoms (prescription, over the counter, or herbal); history with malign disease, undiagnosed uterine bleeding, high blood pressure, medical condition or chronic disease (eg, history of neurological [eg, cognitive], hepatic, renal, cardiovascular, gastrointestinal, pulmonary [eg, moderate asthma], endocrine, or gynaecological disease) or malignancy that could confound interpretation of the study, liver or kidney disease |
| «Johnson KA, Martin N, Nappi RE, ym. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. J Clin Endocrinol Metab 2023;108(8):1981-1997»2 | Inclusion and exclusion criteria were the same as in the Study 1. |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Baseline; Absolut number of moderate to severe vasomotor symptoms per 24 h (SD) | Follow-up; Absolut number of moderate to severe vasomotor symptoms per 24 h (SD) | Relative effect [SE or 95% CI, p] |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to risk of bias (including possible publication bias). | |||||
| «Lederman S, Ottery FD, Cano A, ym. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet 2023;401(10»1 | N (placebo)=175 N (fezolinetant 45 mg)=173 | 12 weeks | Placebo: 10.5 (3.8) Fezolinetant: 10.4 (4.7) | Placebo: 6.9 (4.7) Fezolinetant: 4.1 (3.9) | Fezolinetant 45 mg vs placebo (least squares): -0,24 [SE 0.08; p=0·007]; - 35% for placebo, -61% for fezolinetant 45 mg |
| «Johnson KA, Martin N, Nappi RE, ym. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. J Clin Endocrinol Metab 2023;108(8):1981-1997»2 | N (placebo)=167 N (fexolinetant 45 mg(=176) | 12 weeks | Plecebo (mean, (SD)): 11.59 (5.02) Fezolinetant (mean, (SD)): 11.79 (8.26) | Placebo (mean, (SD)): 6.73 (7.58) Fezolinetant 45 mg (mean, (SD)): 4.49 (5.39) | Fezolinetant vs placebo (Least squares) -2.53, 95% CI –3.60, –1.46. -45.35% for placebo and -62.27% for fezolinetant 45 mg |
I= intervention; C=comparison; CI=confidence interval, SD=standard deviation
| Reference | Number of studies and number of patients (I/C) | Follow-up time | I | C | Relative effect (SE, p) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to possible publication bias. | |||||
| «Lederman S, Ottery FD, Cano A, ym. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet 2023;401(10»1 | N (placebo)=175 N (fezolinetant 45 mg)=173 | 12 weeks | N=149 | N=139 | –0.20 (0.08; p=0.007) |
| «Johnson KA, Martin N, Nappi RE, ym. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. J Clin Endocrinol Metab 2023;108(8):1981-1997»2 | N (placebo)=167 N (fezolinetant 45 mg)=176 | 12 weeks | Daily mean (SE) 1.66 (0.79) | Daily mean (SE) 1.95 (0.68) | -0.29 (95% CI –0.45–0.13) |
I= intervention; C=comparison; CI=confidence interval, SD=stanrad deviation, SE=standars error
References
- Lederman S, Ottery FD, Cano A, ym. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet 2023;401(10382):1091-1102 «PMID: 36924778»PubMed
- Johnson KA, Martin N, Nappi RE, ym. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. J Clin Endocrinol Metab 2023;108(8):1981-1997 «PMID: 36734148»PubMed