Gracies Jean-Michel, Esquenazi Alberto, Brashear Allison, Banach Marta, Kocer Serdar, Jech Robert, Khatkova Svetlana, Benetin Ján, Vecchio Michele, McAllister Peter, Ilkowski Jan, Ochudlo Stanislaw, Catus France, Grandoulier Anne Sophie, Vilain Claire, Picaut Philippe
Author affiliations are provided at the end of the article.
Neurology. 2017 Nov 28;89(22):2245-2253. doi: 10.1212/WNL.0000000000004687. Epub 2017 Nov 1.
To demonstrate single abobotulinumtoxinA injection efficacy in lower limb vs placebo for adults with chronic hemiparesis and assess long-term safety and efficacy of repeated injections.
In a multicenter, double-blind, randomized, placebo-controlled, single-cycle study followed by a 1-year open-label, multiple-cycle extension, adults ≥6 months after stroke/brain injury received one lower limb injection (abobotulinumtoxinA 1,000 U, abobotulinumtoxinA 1,500 U, placebo) followed by ≤4 open-label cycles (1,000, 1,500 U) at ≥12-week intervals. Efficacy measures included Modified Ashworth Scale (MAS) in gastrocnemius-soleus complex (GSC; double-blind primary endpoint), physician global assessment (PGA), and comfortable barefoot walking speed. Safety was the open-label primary endpoint.
After a single injection, mean (95% confidence interval) MAS GSC changes from baseline at week 4 (double-blind, n = 381) were as follows: -0.5 (-0.7 to -0.4) (placebo, n = 128), -0.6 (-0.8 to -0.5) (abobotulinumtoxinA 1,000 U, n = 125; = 0.28 vs placebo), and -0.8 (-0.9 to -0.7) (abobotulinumtoxinA 1,500 U, n = 128; = 0.009 vs placebo). Mean week 4 PGA scores were as follows: 0.7 (0.5, 0.9) (placebo), 0.9 (0.7, 1.1) (1,000 U; = 0.067 vs placebo), and 0.9 (0.7, 1.1) (1,500 U; = 0.067); walking speed was not significantly improved vs placebo. At cycle 4, week 4 (open-label), mean MAS GSC change reached -1.0. Incremental improvements in PGA and walking speed occurred across open-label cycles; by cycle 4, week 4, mean PGA was 1.9, and walking speed increased +25.3% (17.5, 33.2), with 16% of participants walking >0.8 m/s (associated with community mobility; 0% at baseline). Tolerability was good and consistent with the known abobotulinumtoxinA safety profile.
In chronic hemiparesis, single abobotulinumtoxinA (Dysport Ipsen) administration reduced muscle tone. Repeated administration over a year was well-tolerated and improved walking speed and likelihood of achieving community ambulation.
NCT01249404, NCT01251367.
The double-blind phase of this study provides Class I evidence that for adults with chronic spastic hemiparesis, a single abobotulinumtoxinA injection reduces lower extremity muscle tone.
证明单次注射阿柏西普肉毒杆菌毒素A对患有慢性偏瘫的成年人下肢的疗效优于安慰剂，并评估重复注射的长期安全性和疗效。
在一项多中心、双盲、随机、安慰剂对照、单周期研究中，随后进行为期1年的开放标签、多周期扩展研究，中风/脑损伤后≥6个月的成年人接受一次下肢注射（阿柏西普肉毒杆菌毒素A 1000 U、阿柏西普肉毒杆菌毒素A 1500 U、安慰剂），随后在≥12周的间隔内进行≤4个开放标签周期（1000、1500 U）。疗效指标包括腓肠肌-比目鱼肌复合体（GSC）的改良Ashworth量表（MAS；双盲主要终点）、医生整体评估（PGA）和舒适赤脚步行速度。安全性是开放标签的主要终点。
单次注射后，第4周（双盲，n = 381）时，GSC的MAS从基线的平均（95%置信区间）变化如下：-0.5（-0.7至-0.4）（安慰剂，n = 128），-0.6（-0.8至-0.5）（阿柏西普肉毒杆菌毒素A 1000 U，n = 125；与安慰剂相比P = 0.28），以及-0.8（-0.9至-0.7）（阿柏西普肉毒杆菌毒素A 1500 U，n = 128；与安慰剂相比P = 0.009）。第4周的平均PGA评分如下：0.7（0.5，0.9）（安慰剂），0.9（0.7，1.1）（1000 U；与安慰剂相比P = 0.067），以及0.9（0.7，1.1）（1500 U；与安慰剂相比P = 0.067）；与安慰剂相比，步行速度没有显著提高。在第4周期第4周（开放标签）时，GSC的MAS平均变化达到-1.0。在开放标签周期中，PGA和步行速度有渐进性改善；到第4周期第4周时，平均PGA为1.9，步行速度提高了+25.3%（17.5，33.2），16%的参与者步行速度>0.8 m/s（与社区活动能力相关；基线时为0%）。耐受性良好，与已知的阿柏西普肉毒杆菌毒素A安全性概况一致。
在慢性偏瘫中，单次注射阿柏西普肉毒杆菌毒素A（Dysport Ipsen）可降低肌张力。在一年的时间里重复给药耐受性良好，并提高了步行速度和实现社区行走的可能性。
NCT01249404，NCT01251367。
本研究的双盲阶段提供了I级证据，即对于患有慢性痉挛性偏瘫的成年人，单次注射阿柏西普肉毒杆菌毒素A可降低下肢肌张力。
