A 500 U/2 mL dilution of abobotulinumtoxinA vs. placebo: randomized study in cervical dystonia

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. Materials and methods: 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. Results: 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 Conclusions: 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.

研究目的：阿泊肉毒杆菌毒素A（abobotulinumtoxinA），商品名丽舒妥®（Dysport®），由美国新泽西州巴斯金里奇的益普生生物制药公司（Ipsen Biopharmaceuticals, Inc.）生产，是一种乙酰胆碱释放抑制剂及神经肌肉阻滞剂。此前美国阿泊肉毒杆菌毒素A的处方信息仅批准了500U/1mL的稀释方案用于颈肌张力障碍（cervical dystonia）。若有临床试验数据支持采用500U/2mL的更大体积稀释方案，将为临床医师提供注射体积的选择灵活性，进而更好地契合患者需求。材料与方法：本研究开展了一项为期12周的3b期多中心随机双盲安慰剂对照试验（临床试验编号：NCT01753310）。将确诊为原发性颈肌张力障碍的成年受试者按2:1的比例随机分组，分别接受单次注射500U/2mL稀释的阿泊肉毒杆菌毒素A或安慰剂。主要疗效终点为第4周时多伦多西部痉挛性斜颈评定量表（Toronto Western Spasmodic Torticollis Rating Scale）总分较基线的变化值。结果：共134例受试者（阿泊肉毒杆菌毒素A组89例，安慰剂组45例）完成随机分组并纳入意向治疗人群（intent-to-treat population）；其中129例（阿泊肉毒杆菌毒素A组84例，安慰剂组45例）完成了第4周的主要疗效终点评估，纳入改良意向治疗人群（modified intent-to-treat population）。在改良意向治疗人群中，与安慰剂组相比，接受阿泊肉毒杆菌毒素A治疗的受试者在主要疗效终点上较基线出现了更显著的改善（加权总体治疗差异为-8.3，P）。结论：本试验证实，500U/2mL的稀释方案可有效治疗颈肌张力障碍，且其安全性特征与阿泊肉毒杆菌毒素A的已知安全性谱一致。