Aurora Sheena K, Gawel Marek, Brandes Jan L, Pokta Suriani, Vandenburgh Amanda M
Swedish Pain Center, Seattle, WA 98104, USA.
Headache. 2007 Apr;47(4):486-99. doi: 10.1111/j.1526-4610.2006.00624.x.
This exploratory trial evaluated the safety and efficacy of multiple treatments of botulinum toxin type A (BoNTA; BOTOX, Allergan, Inc., Irvine, CA, USA) as prophylactic treatment of episodic migraine headaches.
This was an 11-month randomized, double-blind, placebo-controlled, exploratory study. Patients were screened during a 30-day baseline period, and eligible patients with 4 or more migraine episodes and < or =15 headache days entered a single-blind 30-day placebo run-in period. Patients were classified as placebo nonresponders (PNR) if they had at least 4 moderate-to-severe migraine episodes and did not experience at least a 50% decrease from baseline in the frequency of migraine episodes following their placebo treatment. All other subjects were classified as placebo responders (PR). Patients were randomized within each stratum (PNR, PR) to 3 treatments with BoNTA (110 to 260 U of BoNTA per treatment cycle) or placebo at 90-day intervals using a modified follow-the-pain treatment paradigm. The primary efficacy outcome measure was the mean change from baseline in the frequency of migraine episodes for the 30 days prior to day 180 in the PNR group. Secondary efficacy measures included the proportion of patients with a decrease from baseline of 50% or more migraine episodes per 30-day period. Patients were allowed to take concomitant acute and prophylactic headache medications. Adverse events were reported.
A total of 809 patients were screened and 369 patients (89.2% female; mean age, 45 years; range, 20 to 65 years) entered the placebo run-in period and were subsequently randomized to BoNTA or placebo. The mean total dose of BoNTA was 190.5 units (U) (range, 110 U to 260 U). The predetermined primary efficacy endpoint was not met. Substantial mean improvements of 2.4 and 2.2 fewer migraine episodes per month at day 180 in the PNR stratum treated with BoNTA and placebo, respectively, were observed (P > .999). From day 180 through the end of the study (day 270) at least 50% of all patients in each treatment group had a decrease from baseline of 50% or more migraine episodes per 30-day period. However, in the group of patients with > or =12 headache days at baseline (and < or =15 headache days), BoNTA patients experienced a mean change from baseline of -4.0 headache episodes at day 180 compared with -1.9 headache episodes in the placebo group (P= .048). The majority of treatment-related adverse events were transient and mild to moderate in severity. Only 7 patients (1.9%) discontinued the study due to adverse events (6 BoNTA, 1 placebo).
There were no statistically significant between-group differences in the mean change from baseline in the frequency of migraine episodes per 30-day period. There were substantial, sustained improvements during the course of the study in all groups. Multiple treatments with BoNTA were shown to be safe and well tolerated over an active treatment period lasting 9 months.
本探索性试验评估了多次注射A型肉毒杆菌毒素（BoNTA；保妥适，美国加利福尼亚州欧文市艾尔建公司生产）预防性治疗发作性偏头痛的安全性和有效性。
这是一项为期11个月的随机、双盲、安慰剂对照的探索性研究。在30天的基线期对患者进行筛查，符合条件的有4次或更多偏头痛发作且头痛天数≤15天的患者进入为期30天的单盲安慰剂导入期。如果患者至少有4次中度至重度偏头痛发作，且在接受安慰剂治疗后偏头痛发作频率较基线未降低至少50%，则被分类为安慰剂无反应者（PNR）。所有其他受试者被分类为安慰剂反应者（PR）。采用改良的“追踪疼痛”治疗模式，将每个分层（PNR、PR）内的患者随机分为3组，每90天接受一次BoNTA治疗（每个治疗周期110至260单位BoNTA）或安慰剂治疗。主要疗效指标是PNR组在第180天前30天偏头痛发作频率相对于基线的平均变化。次要疗效指标包括每30天偏头痛发作次数较基线减少50%或更多的患者比例。患者可同时服用急性和预防性头痛药物，并报告不良事件。
共筛查了809例患者，369例患者（89.2%为女性；平均年龄45岁；范围20至65岁）进入安慰剂导入期，随后被随机分为BoNTA组或安慰剂组。BoNTA的平均总剂量为190.5单位（范围110单位至260单位）。未达到预定的主要疗效终点。在接受BoNTA和安慰剂治疗的PNR分层中，在第180天时每月偏头痛发作次数分别显著减少2.4次和2.2次（P>.999）。从第180天到研究结束（第270天），每个治疗组中至少50%的患者每30天偏头痛发作次数较基线减少50%或更多。然而，在基线时有≥12天头痛（且≤15天头痛）的患者组中，BoNTA组患者在第180天时头痛发作次数相对于基线的平均变化为-4.0次，而安慰剂组为-1.9次（P = .048）。大多数与治疗相关的不良事件是短暂的，严重程度为轻度至中度。只有7例患者（1.9%）因不良事件退出研究（6例BoNTA组，1例安慰剂组）。
每30天偏头痛发作频率相对于基线的平均变化在组间无统计学显著差异。在研究过程中所有组均有显著且持续的改善。在长达9个月的积极治疗期内，多次注射BoNTA显示出安全且耐受性良好。
