Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Ann Neurol. 2010 Oct;68(4):494-502. doi: 10.1002/ana.22240.
A previous phase 3 study showed significant improvement in walking ability in multiple sclerosis (MS) patients treated with oral, extended-release dalfampridine (4-aminopyridine) 10mg twice daily. The current study was designed to confirm efficacy and further define safety and pharmacodynamics.
This was a 39-center, double-blind trial in patients with definite MS of any course type. Participants were randomized to 9 weeks of treatment with dalfampridine (10mg twice daily; n = 120) or placebo (n = 119). Response was defined as consistent improvement on the Timed 25-Foot Walk, with percentage of timed walk responders (TWRs) in each treatment group as the primary outcome. The last on-treatment visit provided data from 8 to 12 hours postdose, to examine maintenance of effect.
One patient from each group was excluded from the modified Intention to Treat population. The proportion of TWRs was higher in the dalfampridine group (51/119 or 42.9%) compared to the placebo group (11/118 or 9.3%, p < 0.0001). The average improvement in walking speed among dalfampridine-treated TWRs during the 8-week efficacy evaluation period was 24.7% from baseline (95% confidence interval, 21.0-28.4%); the mean improvement at the last on-treatment visit was 25.7%, showing maintenance of effect over the interdosing period. There were no new safety findings.
This interventional study provides class 1 evidence that dalfampridine extended-release tablets produce clinically meaningful improvement in walking ability in a subset of people with MS, with the effect maintained between doses.
一项先前的 3 期研究表明，口服、缓释二甲弗林（4-氨基吡啶）10mg，每日两次，可显著改善多发性硬化症（MS）患者的步行能力。本研究旨在确认疗效，并进一步确定安全性和药效动力学。
这是一项在任何病程类型的确诊 MS 患者中进行的 39 中心、双盲试验。参与者被随机分为 9 周的达拉非尼治疗（10mg，每日两次；n=120）或安慰剂（n=119）。反应定义为定时 25 英尺行走能力持续改善，每个治疗组的定时行走反应者（TWR）百分比作为主要终点。最后一次治疗访视提供了用药后 8-12 小时的数据，以检查疗效的维持情况。
每组各有一名患者被排除在修改后的意向治疗人群之外。达拉非尼组的 TWR 比例（51/119 或 42.9%）高于安慰剂组（11/118 或 9.3%，p<0.0001）。在 8 周的疗效评估期间，达拉非尼治疗的 TWR 中行走速度的平均改善为基线的 24.7%（95%置信区间，21.0-28.4%）；最后一次治疗访视时的平均改善为 25.7%，显示在两次剂量之间维持了疗效。没有新的安全性发现。
这项干预性研究提供了 1 级证据，表明缓释二甲弗林片可在多发性硬化症患者的亚组中产生有临床意义的行走能力改善，且在两次剂量之间保持疗效。
