Ferrari M D, Roon K I, Lipton R B, Goadsby P J
Department of Neurology, Leiden University Medical Centre, 2300 RC Leiden, Albinusdreef 2, 2333 ZA, Leiden, Netherlands.
Lancet. 2001 Nov 17;358(9294):1668-75. doi: 10.1016/S0140-6736(01)06711-3.
The triptans, selective serotonin 5-HT(1B/1D) agonists, are very effective acute migraine drugs with a well- developed scientific rationale. Seven different triptans will soon be clinically available, making evidence-based selection guidelines necessary. Triptan trials have similar designs, facilitating meta-analysis; this will provide a foundation for using triptans in clinical practice.
We asked pharmaceutical companies and the principal investigators of company-independent trials for raw patient data of all double-blind, randomised, controlled, clinical trials of oral triptans in migraine. We calculated summary estimates across studies for important efficacy and tolerability parameters, and separately summarised direct comparator trials.
53 clinical trials (12 unpublished) involving 24089 patients, met the criteria for inclusion. Mean results for 100 mg sumatriptan were 59% (95% CI 57-60) for 2 h headache response (improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain free by 2 h and no headache recurrence or use of rescue medication 2-24 h post dose); and 67% (63-70) for consistency (response in at least two of three treated attacks); placebo-subtracted proportions for patients with at least one adverse event (AE) were 13% (8-18), for at least one central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these data, 10 mg rizatriptan showed better efficacy and consistency, and similar tolerability; 80 mg eletriptan showed better efficacy, similar consistency, but lower tolerability; 12.5 mg almotriptan showed similar efficacy at 2 h but better other results; 2.5 mg naratriptan and 20 mg eletriptan showed lower efficacy and (the first two) better tolerability; 2.5 mg and 5 mg zolmitriptan, 40 mg eletriptan, and 5 mg rizatriptan showed very similar results. The results of the 22 trials that directly compared triptans show the same overall pattern. We received no data on frovatriptan, but publicly available data suggest lower efficacy.
At marketed doses, all oral triptans were effective and well tolerated. 10 mg rizatriptan, 80 mg eletriptan, and 12.5 mg almotriptan provide the highest likelihood of consistent success.
曲坦类药物，即选择性5-羟色胺5-HT(1B/1D)激动剂，是非常有效的急性偏头痛治疗药物，其科学原理完善。七种不同的曲坦类药物很快将可用于临床，因此有必要制定基于证据的选择指南。曲坦类药物的试验设计相似，便于进行荟萃分析；这将为在临床实践中使用曲坦类药物提供基础。
我们向制药公司及独立于公司的试验的主要研究者索要所有口服曲坦类药物治疗偏头痛的双盲、随机、对照临床试验的原始患者数据。我们计算了各项研究中重要疗效和耐受性参数的汇总估计值，并分别汇总了直接比较试验。
53项临床试验（12项未发表）涉及24089名患者，符合纳入标准。100毫克舒马曲坦2小时头痛缓解（从中度或重度改善为轻度或无痛）的平均结果为59%（95%置信区间57 - 60）；2小时无痛（改善为无痛）的比例为29%（27 - 30）；持续无痛（2小时无痛且给药后2 - 24小时无头痛复发或未使用急救药物）的比例为20%（18 - 21）；一致性（三次治疗发作中至少两次有反应）的比例为67%（63 - 70）；至少有一次不良事件（AE）的患者的安慰剂扣除比例为13%（8 - 18），至少有一次中枢神经系统AE的比例为6%（3 - 9），至少有一次胸部AE的比例为1.9%（1.0 - 2.7）。与这些数据相比，10毫克利扎曲坦显示出更好的疗效和一致性，以及相似的耐受性；80毫克依立曲坦显示出更好的疗效、相似的一致性，但耐受性较低；12.5毫克阿莫曲坦在2小时时显示出相似的疗效，但其他结果更好；2.5毫克那拉曲坦和20毫克依立曲坦显示出较低的疗效，且（前两者）耐受性较好；2.5毫克和5毫克佐米曲坦、40毫克依立曲坦以及5毫克利扎曲坦显示出非常相似的结果。22项直接比较曲坦类药物的试验结果显示出相同的总体模式。我们未收到夫罗曲坦的数据，但公开可得的数据表明其疗效较低。
在上市剂量下，所有口服曲坦类药物均有效且耐受性良好。10毫克利扎曲坦、80毫克依立曲坦和12.5毫克阿莫曲坦持续成功的可能性最高。
