OnabotulinumtoxinA for Treatment of Chronic Migraine: Pooled Analyses of the 56-Week PREEMPT Clinical Program
OnabotulinumtoxinA for Treatment of Chronic Migraine: Pooled Analyses of the 56-Week PREEMPT Clinical Program
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DOI：
10.1111/j.1526-4610.2011.01990.x
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发表时间：
2011-10-01
期刊：
影响因子：
5
通讯作者：
Turkel, Catherine C.
中科院分区：
文献类型：
--
作者：
Aurora, Sheena K.;Winner, Paul;Turkel, Catherine C.
目的：评估奥托林毒素A(Botox(R))预防成人慢性偏头痛的安全性和有效性。背景：慢性偏头痛是一种普遍的、致残的、未得到充分治疗的神经系统疾病。设计与方法--两个第三阶段，为期24周的双盲、平行分组、安慰剂对照研究，以及随后为期32周的开放标签、单一治疗的OnabotulinumoxinA阶段研究(2006年1月23日至2008年8月11日)。符合条件的受试者被随机(1：1)注射奥曲霉毒素A(155-195U)或安慰剂，每12周注射一次，共5个周期(双盲：2，开放标记：3)。合并的主要变量是头痛天数与基线相比的平均变化。次要变量包括重度头痛影响测试-6评分(>；=60)的患者比例以及偏头痛天数、中度/重度头痛天数和偏头痛发作次数与基线相比的平均变化；头痛天数的累计头痛小时数；以及急性头痛药物摄入量。主要的时间点是第24周。对开放标签阶段(所有患者均接受onabotulinumoxinA治疗)的评估与双盲治疗组(onabotulinumoxinA/onabotulinumoxinA与安慰剂/onabotulinoxinA相比)进行比较，并进行总结，以描述一致的研究结果，与统计学意义有关的推论仅考察56周。结果：在双盲阶段，共有1384名患者被随机分为onabotulinA(n=688)或安慰剂(n=696)；607(88.2%)onabotulinA/onabotulinoxinA患者和629(90.4%)abotulinoxinA患者继续进入开放标签阶段。在治疗第56周时，与服用安慰剂/使用安慰剂/使用安慰剂相比，使用安慰剂/使用安慰剂A相比，服用安慰剂/使用安慰剂/使用安慰剂A的慢性偏头痛患者在第56周时头痛次数显著减少(分别为-11.7和-10.8；P=.019)。统计上显著的减少也有利于在第56周的几个次级疗效变量中，包括偏头痛天数(-11.2onabotulinumoxinA/onabotulinumoxinA，-10.3onabotulinumoxinA；P=.018)和中度/重度头痛天数(-10.7onabotulinA/onabotulinoxinA，-9.9安慰剂/onabotulinoxinA；P=.027)和头痛天数的累计头痛小时数(-169.1 onabotulinA/onabulinoxinA；P=.018)。在开放标签阶段(全部用奥纳博林毒素A治疗)后，观察到所有疗效变量在组内较基线有统计学意义的变化。大多数患者(72.6%)完成了开放标签阶段；少数患者因不良事件而停用。没有新的安全性或耐受性问题出现。结论-重复治疗
Objective.-To evaluate safety and efficacy of onabotulinumtoxinA (BOTOX (R)) as headache prophylaxis in adults with chronic migraine.Background.-Chronic migraine is a prevalent, disabling, and undertreated neurological disorder. OnabotulinumtoxinA is the only approved prophylactic therapy in this highly disabled patient population.Design and Methods.-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.Results.-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.Conclusions.-Repeated treatment with