Swedish Neuroscience Institute, Seattle, WA, USA.
Headache. 2011 Oct;51(9):1358-73. doi: 10.1111/j.1526-4610.2011.01990.x. Epub 2011 Aug 29.
To evaluate safety and efficacy of onabotulinumtoxinA (BOTOX(®) ) as headache prophylaxis in adults with chronic migraine.
Chronic migraine is a prevalent, disabling, and undertreated neurological disorder. OnabotulinumtoxinA is the only approved prophylactic therapy in this highly disabled patient population.
Two phase III, 24-week, double-blind, parallel-group, placebo-controlled studies, followed by a 32-week, open-label, single-treatment, onabotulinumtoxinA phase, were conducted (January 23, 2006 to August 11, 2008). Qualified subjects were randomized (1:1) to injections of onabotulinumtoxinA (155-195 U) or placebo every 12 weeks for 5 cycles (double-blind: 2, open-label: 3). The pooled primary variable was mean change from baseline in frequency of headache days. Secondary variables included proportion of patients with severe Headache Impact Test-6 score (≥ 60) and mean changes from baseline in frequencies of migraine days, moderate/severe headache days, and migraine episodes; cumulative hours of headache on headache days; and acute headache medication intakes. The primary time point was week 24. Assessments for the open-label phase (all patients treated with onabotulinumtoxinA) compared double-blind treatment groups (onabotulinumtoxinA/onabotulinumtoxinA vs placebo/onabotulinumtoxinA) and are summarized to give a descriptive view of consistent study results, with inferences regarding statistical significance only examined for week 56.
A total of 1384 patients were randomized to onabotulinumtoxinA (n = 688) or placebo (n = 696) in the double-blind phase; 607 (88.2%) onabotulinumtoxinA/onabotulinumtoxinA and 629 (90.4%) placebo/onabotulinumtoxinA patients continued into the open-label phase. OnabotulinumtoxinA/onabotulinumtoxinA treatment statistically significantly reduced headache-day frequency vs placebo/onabotulinumtoxinA in patients with chronic migraine at week 56 (-11.7 onabotulinumtoxinA/onabotulinumtoxinA, -10.8 placebo/onabotulinumtoxinA; P = .019). Statistically significant reductions also favored onabotulinumtoxinA/onabotulinumtoxinA for several secondary efficacy variables at week 56, including frequencies of migraine days (-11.2 onabotulinumtoxinA/onabotulinumtoxinA, -10.3 placebo/onabotulinumtoxinA; P = .018) and moderate/severe headache days (-10.7 onabotulinumtoxinA/onabotulinumtoxinA, -9.9 placebo/onabotulinumtoxinA; P = .027) and cumulative headache hours on headache days (-169.1 onabotulinumtoxinA/onabotulinumtoxinA, -145.7 placebo/onabotulinumtoxinA; P = .018). After the open-label phase (all treated with onabotulinumtoxinA), statistically significant within-group changes from baseline were observed for all efficacy variables. Most patients (72.6%) completed the open-label phase; few discontinued because of adverse events. No new safety or tolerability issues emerged.
Repeated treatment with ≤ 5 cycles of onabotulinumtoxinA was effective, safe, and well tolerated in adults with chronic migraine.
评估成批肉毒毒素（BOTOX(®)）作为慢性偏头痛成人预防性治疗的安全性和有效性。
慢性偏头痛是一种常见、使人丧失能力且治疗不足的神经系统疾病。成批肉毒毒素是该高度失能患者群体中唯一批准的预防性治疗方法。
两项为期 24 周、双盲、平行组、安慰剂对照的 3 期研究，随后进行为期 32 周的开放性、单治疗、成批肉毒毒素阶段，于 2006 年 1 月 23 日至 2008 年 8 月 11 日进行。合格的受试者被随机（1:1）接受成批肉毒毒素（155-195U）或安慰剂，每 12 周注射一次，共 5 个周期（双盲：2 个周期，开放性：3 个周期）。汇总的主要变量是从基线到头痛天数的平均变化。次要变量包括严重头痛影响测试-6 评分（≥60）的患者比例（≥60）和从基线到偏头痛天数、中度/重度头痛天数和偏头痛发作频率的平均变化；头痛日的累积头痛时间；以及急性头痛药物摄入量。主要时间点为第 24 周。开放性阶段的评估（所有接受成批肉毒毒素治疗的患者）比较了双盲治疗组（成批肉毒毒素/成批肉毒毒素与安慰剂/成批肉毒毒素），并进行了总结，以提供一致研究结果的描述性视图，仅对第 56 周进行了关于统计学意义的推断。
共有 1384 名患者被随机分配到成批肉毒毒素（n=688）或安慰剂（n=696）的双盲阶段；607（88.2%）的成批肉毒毒素/成批肉毒毒素和 629（90.4%）的安慰剂/成批肉毒毒素患者继续进入开放性阶段。与安慰剂/成批肉毒毒素相比，成批肉毒毒素/成批肉毒毒素治疗在慢性偏头痛患者中在第 56 周时显著降低了头痛日频率（成批肉毒毒素/成批肉毒毒素减少 11.7，安慰剂/成批肉毒毒素减少 10.8；P=0.019）。在第 56 周时，成批肉毒毒素/成批肉毒毒素也显著有利于几个次要疗效变量，包括偏头痛天数（成批肉毒毒素/成批肉毒毒素减少 11.2，安慰剂/成批肉毒毒素减少 10.3；P=0.018）和中度/重度头痛天数（成批肉毒毒素/成批肉毒毒素减少 10.7，安慰剂/成批肉毒毒素减少 9.9；P=0.027）和头痛日的累积头痛时间（成批肉毒毒素/成批肉毒毒素减少 169.1，安慰剂/成批肉毒毒素减少 145.7；P=0.018）。在开放性阶段（所有患者均接受成批肉毒毒素治疗）后，所有疗效变量均观察到了与基线相比的显著的组内变化。大多数患者（72.6%）完成了开放性阶段；少数患者因不良事件而停药。没有出现新的安全性或耐受性问题。
重复治疗 5 个周期或以下的成批肉毒毒素对慢性偏头痛成人是有效、安全和耐受良好的。
