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阿柏西普肉毒素A液体制剂治疗颈部肌张力障碍的疗效与安全性:一项随机对照试验。

Efficacy and safety of abobotulinumtoxinA liquid formulation in cervical dystonia: A randomized-controlled trial.

作者信息

Poewe Werner, Burbaud Pierre, Castelnovo Giovanni, Jost Wolfgang H, Ceballos-Baumann Andres O, Banach Marta, Potulska-Chromik Anna, Ferreira Joaquim J, Bihari Katalin, Ehler Edvard, Bares Martin, Dzyak Lyudmyla A, Belova Anna N, Pham Emmanuel, Liu Wenzhong Jerry, Picaut Philippe

机构信息

Department of Neurology, Innsbruck Medical University/University Hospital, Innsbruck, Austria.

Department of Clinical Neurophysiology, CHU de Bordeaux, Bordeaux, France.

出版信息

Mov Disord. 2016 Nov;31(11):1649-1657. doi: 10.1002/mds.26760. Epub 2016 Sep 21.

Abstract

BACKGROUND

Approved botulinum toxin A products require reconstitution. AbobotulinumtoxinA solution for injection is a ready-to-use liquid formulation of abobotulinumtoxinA.

OBJECTIVES

The objective of this study was to demonstrate the superior efficacy of abobotulinumtoxinA solution for injection to placebo and to test the noninferior efficacy of abobotulinumtoxinA solution for injection versus abobotulinumtoxinA (dry formulation) in cervical dystonia.

METHODS

This was a phase-3, multicenter, prospective, double-blind, randomized, active, and placebo-controlled study (N = 369). Patients with cervical dystonia were randomized (3:3:1) to abobotulinumtoxinA solution for injection 500 U, abobotulinumtoxinA 500 U, or placebo. Following the double-blind phase, patients received abobotulinumtoxinA solution for injection, open-label, for up to 4 cycles. The primary outcome was change from baseline at week 4 of the Toronto Western Spasmodic Torticollis Rating Scale total score. Secondary measures included change from baseline or cycle baseline in Toronto Western Spasmodic Torticollis Rating Scale scores.

RESULTS

At week 4, both products were superior to placebo (Toronto Western Spasmodic Torticollis Rating Scale total score least square mean decrease from baseline, abobotulinumtoxinA solution for injection 500 U -12.5, abobotulinumtoxinA 500 U -14.0, placebo -3.9; P < .0001 vs placebo). The noninferiority limit of 3 points in the Toronto Western Spasmodic Torticollis Rating Scale total score at week 4 was not met for abobotulinumtoxinA solution for injection versus abobotulinumtoxinA. Toronto Western Spasmodic Torticollis Rating Scale total score reductions were maintained for up to 4 cycles of abobotulinumtoxinA solution for injection open-label follow-up treatment. Safety profiles of abobotulinumtoxinA solution for injection and abobotulinumtoxinA were similar, with dysphagia and injection-site pain the most frequent drug-related adverse events.

CONCLUSIONS

Although the predefined noninferiority criterion was not met, abobotulinumtoxinA solution for injection was similarly effective to freeze-dried abobotulinumtoxinA in reducing Toronto Western Spasmodic Torticollis Rating Scale total scores with a similar safety profile. AbobotulinumtoxinA solution for injection efficacy was maintained with chronic open-label treatment, and this novel formulation may add convenience as well as dosing accuracy to treatment with abobotulinumtoxinA. © 2016 International Parkinson and Movement Disorder Society.

摘要

背景

已获批的A型肉毒毒素产品需要重新配置。注射用阿柏西普肉毒毒素A溶液是一种即用型的阿柏西普肉毒毒素A液体制剂。

目的

本研究的目的是证明注射用阿柏西普肉毒毒素A溶液相对于安慰剂具有更高的疗效,并测试注射用阿柏西普肉毒毒素A溶液与阿柏西普肉毒毒素A(冻干制剂)在治疗颈部肌张力障碍方面的非劣效性疗效。

方法

这是一项3期、多中心、前瞻性、双盲、随机、活性药物和安慰剂对照研究(N = 369)。颈部肌张力障碍患者被随机分组(3:3:1),分别接受500 U注射用阿柏西普肉毒毒素A溶液、500 U阿柏西普肉毒毒素A或安慰剂治疗。双盲期结束后,患者接受开放标签的注射用阿柏西普肉毒毒素A溶液治疗,最多4个周期。主要结局指标是多伦多西部痉挛性斜颈评定量表总分在第4周时相对于基线的变化。次要测量指标包括多伦多西部痉挛性斜颈评定量表评分相对于基线或周期基线的变化。

结果

在第4周时,两种产品均优于安慰剂(多伦多西部痉挛性斜颈评定量表总分从基线的最小二乘均值下降,500 U注射用阿柏西普肉毒毒素A为-12.5,500 U阿柏西普肉毒毒素A为-14.0,安慰剂为-3.9;与安慰剂相比,P <.0001)。注射用阿柏西普肉毒毒素A溶液与阿柏西普肉毒毒素A相比,未达到第4周时多伦多西部痉挛性斜颈评定量表总分非劣效性界限3分的标准。在开放标签的注射用阿柏西普肉毒毒素A溶液随访治疗的4个周期内,多伦多西部痉挛性斜颈评定量表总分持续降低。注射用阿柏西普肉毒毒素A溶液和阿柏西普肉毒毒素A的安全性概况相似,吞咽困难和注射部位疼痛是最常见的与药物相关的不良事件。

结论

虽然未达到预先定义的非劣效性标准,但注射用阿柏西普肉毒毒素A溶液在降低多伦多西部痉挛性斜颈评定量表总分方面与冻干阿柏西普肉毒毒素A同样有效,且安全性概况相似。注射用阿柏西普肉毒毒素A溶液在长期开放标签治疗中疗效得以维持,这种新型制剂可能会增加阿柏西普肉毒毒素A治疗的便利性和给药准确性。© 2016国际帕金森病和运动障碍协会

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