Lew Mark F, Brashear Allison, Dashtipour Khashayar, Isaacson Stuart, Hauser Robert A, Maisonobe Pascal, Snyder Daniel, Ondo William
a Department of Neurology , Keck/University of Southern California School of Medicine , Los Angeles , CA , USA.
b Department of Neurology , Wake Forest School of Medicine , Medical Center Blvd. Winston Salem , NC , USA.
Int J Neurosci. 2018 Jul;128(7):619-626. doi: 10.1080/00207454.2017.1406935. Epub 2018 Jan 17.
Purpose/aim: AbobotulinumtoxinA (Dysport®, Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ, USA) is an acetylcholine release inhibitor and a neuromuscular blocking agent. The United States prescribing information for abobotulinumtoxinA previously indicated only one dilution for cervical dystonia: 500 U/1 mL. Clinical trial data supporting a larger volume with a 500 U/2 mL dilution would offer clinicians flexibility with injection volume to better meet patient needs.
We conducted a 12-week, phase 3b, multicenter, randomized, double-blind, placebo-controlled trial (NCT01753310). Adult subjects with a primary diagnosis of cervical dystonia were randomized (2:1) to receive a single injection of either abobotulinumtoxinA, 500 U/2 mL dilution, or placebo. The primary efficacy endpoint was changed from baseline in Toronto Western Spasmodic Torticollis Rating Scale total score at Week 4.
A total of 134 subjects (abobotulinumtoxinA, n = 89; placebo, n = 45) were randomized (intent-to-treat population) and 129 (abobotulinumtoxinA, n = 84; placebo, n = 45) completed the Week 4 primary endpoint evaluation (modified intent-to-treat population). In the modified intent-to-treat population, subjects receiving abobotulinumtoxinA experienced significantly greater changes from baseline versus placebo on the primary endpoint (weighted overall treatment difference -8.3, P < 0.001). The most common treatment-emergent adverse events (TEAEs) were dysphagia, muscle weakness, neck pain and headache. Overall, TEAEs were consistent with those reported in the abobotulinumtoxinA prescribing information (1 mL dilution) for cervical dystonia patients.
This trial provides evidence that a 500 U/2 mL dilution is an effective treatment for cervical dystonia and exhibits a safety profile consistent with the known safety profile of abobotulinumtoxinA.
目的/目标：阿柏他毒素A（商品名：Dysport®，美国新泽西州巴斯金里奇市益普生生物制药公司生产）是一种乙酰胆碱释放抑制剂和神经肌肉阻滞剂。美国阿柏他毒素A的处方信息之前仅表明用于颈部肌张力障碍的一种稀释液：500单位/1毫升。支持500单位/2毫升稀释液更大体积的临床试验数据将为临床医生提供注射体积的灵活性，以更好地满足患者需求。
我们进行了一项为期12周的3b期、多中心、随机、双盲、安慰剂对照试验（NCT01753310）。原发性颈部肌张力障碍的成年受试者被随机分组（2:1），接受单次注射阿柏他毒素A（500单位/2毫升稀释液）或安慰剂。主要疗效终点是第4周时多伦多西部痉挛性斜颈评定量表总分相对于基线的变化。
总共134名受试者（阿柏他毒素A组，n = 89；安慰剂组，n = 45）被随机分组（意向性治疗人群），129名（阿柏他毒素A组，n = 84；安慰剂组，n = 45）完成了第4周主要终点评估（改良意向性治疗人群）。在改良意向性治疗人群中，接受阿柏他毒素A治疗的受试者在主要终点上相对于安慰剂组，从基线的变化显著更大（加权总体治疗差异-8.3，P < 0.001）。最常见的治疗中出现的不良事件（TEAE）是吞咽困难、肌肉无力、颈部疼痛和头痛。总体而言，TEAE与阿柏他毒素A用于颈部肌张力障碍患者的处方信息（1毫升稀释液）中报告的一致。
该试验提供了证据，表明500单位/2毫升稀释液是治疗颈部肌张力障碍的有效方法，并且其安全性与阿柏他毒素A已知的安全性一致。
