Background

Migraine patients want acute treatment to provide complete relief of the migraine attack within 30 minutes. Traditionally, “speed of onset of effect” is evaluated by estimating the time-point for first statistical separation of drug and placebo. The estimated onset of effect can be a few percent difference of patients being pain free in very large randomised, controlled trials. This difference, however, can be clinically irrelevant.

Methods

Placebo-controlled randomised, controlled trials with pain freedom results from 30 min to 2–4 hours were retrieved from the literature. For each time-point, the therapeutic gain (drug minus placebo) (TG) was calculated. Therapeutic gain for being pain free of 5% was chosen for the definition of “onset of action”, since this is approximately 1/3 of the 16% TG and 1/4 of 21% of TG for sumatriptan 50 mg and 100 mg, respectively.

Results

A total of 22 time-effect curves based on randomised, controlled trials were analysed. Based on the “onset of action” of 5% pain freedom, the evaluated drugs and administration forms can be classified as follows: i) Early time to onset, ≤30 min (three randomised, controlled trials); ii) medium time to onset, 60 min (nine randomised, controlled trials); iii) delayed time to onset, 90–120 min (10 randomised, controlled trials).

Conclusion

Only three non-oral administration forms with a triptan (subcutaneous sumatriptan and nasal zolmitriptan) resulted in an “onset of action” at ≥30 min; in the future, early onset of action should be a priority in the development of new drugs or new administration-forms for the treatment of acute migraine attacks.

中文翻译：

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安慰剂对照偏头痛发作试验中的作用开始：文献综述和建议。

背景

偏头痛患者需要急性治疗以在 30 分钟内完全缓解偏头痛发作。传统上，“起效速度”是通过估计药物和安慰剂首次统计分离的时间点来评估的。在非常大的随机对照试验中，估计的起效可能是无痛患者的几个百分点差异。然而，这种差异在临床上可能无关紧要。

方法

从文献中检索了 30 分钟至 2-4 小时无疼痛结果的安慰剂对照随机对照试验。对于每个时间点，计算治疗增益（药物减去安慰剂）（TG）。选择无痛 5% 的治疗增益来定义“起效”，因为对于舒马曲坦 50 毫克和 100 毫克，这大约是 16% TG 的 1/3 和 21% TG 的 1/4，分别。

结果

对基于随机对照试验的总共 22 条时间效应曲线进行了分析。根据 5% 无痛的“起效”，评估的药物和给药形式可分为以下几类： i) 起效时间早，≤30 分钟（三项随机对照试验）；ii) 发病的中等时间，60 分钟（九项随机对照试验）；iii) 延迟发作时间，90-120 分钟（10 项随机对照试验）。

结论

只有三种曲坦类非口服给药形式（皮下舒马曲坦和经鼻佐米曲坦）在≥30 分钟时“起效”；未来，早期起效应成为开发治疗急性偏头痛发作的新药或新给药形式的优先事项。