PHILADELPHIA (EGMN) –OnabotulinumtoxinA appears to be a safe, effective, and well-tolerated headache prophylactic for patients with chronic migraine.
Two large randomized controlled trials showed that the toxin significantly reduced migraine frequency and improved headache-related disability over 24 weeks, Dr. David W. Dodick reported at the International Headache Congress.
The studies – PREEMPT 1 and 2 – were conducted at 22 centers in North America and Europe, and included 1,384 patients (average age 41 years).
Each trial consisted of a 4-week baseline period, during which patients kept a daily headache diary, followed by 24 weeks of treatment during which patients received two injection cycles of either placebo or onabotulinumtoxinA (Botox), which has not been approved by the Food and Drug Administration for migraine prophylaxis. From 24-56 weeks, there was an open-label trial consisting of three injection cycles of the study drug, said Dr. Dodick of the Mayo Clinic Arizona, Phoenix.
At baseline, patients reported a mean of 20 headache days per month, 19 of which were considered migraine days, with a mean of 290 cumulative headache hours. The mean score on the Headache Impact Test-6 (HIT-6) survey was 65, indicating severe impact. Most of the patients (93%) also reported severe headache-related disability, and 65% were overusing acute pain medications.
During the double-blind phase, patients randomized to the treatment group received two injection cycles (one every 12 weeks) of onabotulinumtoxinA 155 U. The medication was injected at 31 sites across seven muscle areas in the head and neck. At the physicians’ discretion, an additional 40 units could be injected among three additional muscle groups, The maximum dose was 195 U.
The study’s main endpoint was frequency of headache days. Secondary endpoints were frequency of migraine days, moderate/severe headache days, monthly headache hours, and proportion of patients with a severe HIT-6 score.
At 24 weeks, patients in the active group had a significantly greater reduction in headache days and migraine days than those taking placebo (-8 vs. -6, respectively). The HIT-6 score also declined significantly more among the active group (-5 points vs. -2 points). Patients receiving the study drug experienced a greater decrease in cumulative headache hours per month (-120 vs. -80 hours), and a lower proportion had a severe score on the HIT-6 survey (68% vs. 78%).
“The only outcome that was not statistically significantly better among the active group than the placebo group was the percentage overusing acute pain medications,” Dr. Dodick said. “However, the use of triptans did decrease significantly in the active group compared to the placebo group.”
Adverse events occurred in 62% of those taking the study drug and 52% of those taking placebo – a significant difference. There were also significantly more treatment-related adverse events in the onabotulinumtoxinA group (29% vs. 13%). One serious treatment-related adverse event did occur in the active group – a severe post-injection migraine that required hospitalization. Adverse events occurring in more than 5% of the entire study group were neck pain (9%) and upper respiratory infection (5%). Four patients in the active group and one in the placebo group discontinued active injections because of an adverse event.
The study was sponsored by Allergan Inc., manufacturer of the study drug. Dr. Dodick reported having received honoraria from the company.
Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
费城(EGMN)——研究发现A型肉毒杆菌毒素是慢性偏头痛患者的一种安全、有效且耐受性良好的预防头痛药物。
David W. Dodick医生在国际头痛大会上报告，两项大型随机对照试验显示这种毒素可在24周内显著降低偏头痛的发作频率并改善头痛相关失能。
这两项研究（PREEMPT 1和PREEMPT 2）共纳入来自北美和欧洲的22个研究中心的1,384例患者（平均年龄41岁）。
每项研究包括一个为期4周的基线阶段，在此期间患者每日记录头痛日记，随后为一个24周的治疗阶段，在此期间患者接受2个注射周期的安慰剂或A 型肉毒杆菌毒素（Botox，保妥适）治疗，目前美国食品药品管理局（FDA）尚未批准其用于偏头痛的预防。亚利桑那州凤凰城Mayo诊所的Dodick医生说，研究的第24～56周为一个包括研究药物3个治疗周期的开放标记试验。
基线时，患者报告平均每月有20天头痛发作，其中19天视为偏头痛发作日，平均每月的累计头痛发作时间为290h。头痛影响测试-6 （HIT-6）调查量表的平均评分为65，提示影响严重。多数患者（93%）同时报告严重头痛相关失能，并且65%的患者中存在急性镇痛药物过量使用。
在双盲治疗阶段，随机分配到活性治疗组的患者接受了包括两个注射周期（每个周期为12周）的A型肉毒杆菌毒素 155 U治疗。分别于头部和颈部的7个肌肉区域的31个位点注射药物，并可根据医生的决定，在另外3个肌群中追加注射40u的药物，最大用药剂量为195u 。
研究的主要终点为每月头痛发生日数，次要终点为每月偏头痛发作天数、中重度头痛发作天数、每月头痛发作小时数以及HIT-6评分高分患者所占比例。
24周时，活性治疗组患者每月头痛和偏头痛发作天数均较安慰剂组显著减少（分别减少8天和6天），并且活性治疗组的HIT-6评分也显著降低（分别减少5分和2分）。接受研究药物治疗者每月累计头痛发作小时数的减少幅度更大（分别减少120和80小时），且HIT-6调查评分提示影响严重的患者比例更低（分别为68% 和78%）。
Dodick医生说，“活性治疗组与安慰剂组相比，唯一改善未达到统计学差异的指标为急性镇痛药物过量使用的百分率，但活性治疗组曲坦类药物的使用较安慰剂组显著减少。”
活性研究药物组和安慰剂组不良事件发生率分别为62%和52%，具有统计学差异。A型肉毒杆菌毒素组治疗相关不良事件也显著增多（分别为29% 和13%）。活性治疗组发生1例严重治疗相关不良事件——需住院治疗的严重注射后偏头痛。整个研究人群中发生率超过5%的不良事件为颈项疼痛（9%）和上呼吸道感染（5%）。活性治疗组中的4例患者和安慰剂组中的1例患者因不良事件而停止药物注射治疗。
该研究的发起者为保妥适的生产商爱力根公司，Dodick医生报告接受了该公司的酬金。
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