更年期引起的中重度血管舒张症状的非唑烷酮治疗:两项三期研究(SKYLIGHT 1 和 2)中内在和外在因素的影响。

IF 2.8 3区 医学 Q1 OBSTETRICS & GYNECOLOGY
Nanette Santoro, Rossella E Nappi, Genevieve Neal-Perry, Marci English, Deanna D King, Yusuke Yamaguchi, Faith D Ottery
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引用次数: 0

摘要

研究目的本研究旨在利用SKYLIGHT 1和2的12周汇总数据,根据可能影响中重度血管运动症状(VMS)频率和严重程度的几个内在(与个体相关)和外在(外部影响)因素,评估神经激肽3受体拮抗剂非索内酯的疗效:SKYLIGHT 1和2是两项3期随机双盲研究,分别于2019年7月至2021年8月(SKYLIGHT 1)或2021年4月(SKYLIGHT 2)进行。参与者最初被随机分配接受每日剂量的安慰剂、30 毫克 fezolinetant 或 45 毫克 fezolinetant。12周后,安慰剂受试者被重新随机分配到接受非唑来坦30毫克或45毫克,而接受非唑来坦的受试者则继续接受相同剂量的非唑来坦。VMS频率从基线到第12周的变化被用来根据几个内在和外在因素评估疗效。此外,还对总体疗效和安全性进行了调查:共纳入了 1,022 人。在所有内在和外在因素中,非索内酯都能有效降低VMS频率。自我认同为黑人的参与者(非索奈坦 45 毫克与安慰剂的最小二乘法平均差为-3.67;95% CI,-5.32 至-2.01)、当前吸烟者(-3.48;-5.19 至-1.77)和当前饮酒者(-3.48;-4.42 至-2.54)的疗效最为显著。fezolinetant 45 毫克对安慰剂的总体疗效为-2.51(95% CI,-3.20 至-1.82)。fezolinetant 30 毫克剂量也观察到类似的结果。安慰剂(342人中有132人[38.6%])、非佐林内酯30毫克(340人中有132人[38.8%])和非佐林内酯45毫克(340人中有135人[39.7%])的治疗突发不良事件发生率相当:在 SKYLIGHT 1 和 SKYLIGHT 2 中,所分析的内在和外在因素均未显著降低非唑内酯的疗效反应。这些数据为在不同的 VMS 患者中使用非唑来奈坦提供了更多信心。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fezolinetant treatment of moderate-to-severe vasomotor symptoms due to menopause: effect of intrinsic and extrinsic factors in two phase 3 studies (SKYLIGHT 1 and 2).

Objective: This study aimed to assess the efficacy of the neurokinin 3 receptor antagonist, fezolinetant, according to several intrinsic (individual related) and extrinsic (external influence) factors that may influence the frequency and severity of moderate-to-severe vasomotor symptoms (VMS) using pooled 12-week data from SKYLIGHT 1 and 2.

Methods: SKYLIGHT 1 and 2 were two phase 3, randomized, double-blind studies conducted from July 2019 to August 2021 (SKYLIGHT 1) or April 2021 (SKYLIGHT 2). Participants were initially randomized to receive daily doses of placebo, fezolinetant 30 mg, or fezolinetant 45 mg. After 12 weeks, placebo participants were rerandomized to receive fezolinetant 30 mg or 45 mg, whereas those receiving fezolinetant continued on the same dose. Change in VMS frequency from baseline to week 12 was used to assess efficacy according to several intrinsic and extrinsic factors. Overall efficacy and safety were also investigated.

Results: Overall, 1,022 individuals were included. Fezolinetant was efficacious in reducing VMS frequency across all intrinsic and extrinsic factors. Efficacy was most notable for participants who self-identify as Black (least squares mean difference for fezolinetant 45 mg versus placebo, -3.67; 95% CI, -5.32 to -2.01), current smokers (-3.48; -5.19 to -1.77), and current alcohol users (-3.48; -4.42 to -2.54). Overall efficacy was -2.51 (95% CI, -3.20 to -1.82) for fezolinetant 45 mg versus placebo. Similar findings were observed for the fezolinetant 30 mg dose. Comparable incidences of treatment-emergent adverse events were observed for placebo (132 of 342 individuals [38.6%]), fezolinetant 30 mg (132 of 340 individuals [38.8%]), and fezolinetant 45 mg (135 of 340 individuals [39.7%]).

Conclusions: None of the intrinsic and extrinsic factors analyzed substantially reduced the efficacy response to fezolinetant in SKYLIGHT 1 and 2. These data provide additional confidence for using fezolinetant in a diverse population of individuals with VMS.

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来源期刊
CiteScore
5.40
自引率
7.40%
发文量
330
审稿时长
3-8 weeks
期刊介绍: ​Menopause, published monthly, provides a forum for new research, applied basic science, and clinical guidelines on all aspects of menopause. The scope and usefulness of the journal extend beyond gynecology, encompassing many varied biomedical areas, including internal medicine, family practice, medical subspecialties such as cardiology and geriatrics, epidemiology, pathology, sociology, psychology, anthropology, and pharmacology. This forum is essential to help integrate these areas, highlight needs for future research, and enhance health care.
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