Freitag Frederick G, Finlayson Gary, Rapoport Alan M, Elkind Arthur H, Diamond Merle L, Unger Jeffrey R, Fisher Alan C, Armstrong Robert B, Hulihan Joseph F, Greenberg Steven J
Diamond Headache Clinic, Ltd, Chicago, IL 60614, USA.
Headache. 2007 Apr;47(4):519-30. doi: 10.1111/j.1526-4610.2007.00756.x.
To determine whether time-based early treatment, independent of pain intensity, is superior to a pain intensity-based treatment, where patients are asked to treat at least moderate intensity headaches, resulting in a reduction of overall migraine headache duration.
Retrospective and prospective trials have reported improved outcomes when triptans were used early or to treat mild migraine headache pain. However, tolerability as well as efficacy may be 2 of several key issues that have prevented this new treatment paradigm from becoming universally accepted.
In this multicenter, open-label, cluster-randomized study, patients with IHS-defined migraine were instructed to treat 2 sequential migraine headaches with almotriptan 12.5 mg using either Early Treatment (ET, ie, treat at earliest onset of headache pain, within 1 hour) or Standard Treatment (ST, ie, treat when headache pain intensity is moderate or severe). The novel trial design uses total migraine headache pain duration as the primary endpoint.
Results are presented for the first headache and include an ITT population of 757 ET and 693 ST patients. Median headache duration (time from onset of headache pain until no pain) was significantly shorter in ET patients compared to ST patients (3.18 vs 5.53 hours, P < .001). An analysis of the ET subgroup treating headache pain within 1 hour of onset revealed pain intensity, ie, treating mild or moderate versus severe pain, was significantly correlated with treatment outcomes defined by total headache duration, 2-hour pain free, sustained pain free, and use of rescue medication. Multivariate analyses comparing ST subgroups that treated within 1 hour versus greater than 1 hour after headache onset, demonstrate that both pain intensity, ie, treating moderate versus severe headache pain, and treating early versus late, were significantly correlated with total headache duration, 2-hour pain free, sustained pain free, and use of rescue medication. The overall incidence of adverse events was low; nausea and dizziness were the only adverse events with an incidence > or =1% in either treatment group (nausea: 2.5% and 1.7% and dizziness 1.1% and 0.7%, in the ET and ST groups, respectively).
Total headache duration was significantly shorter in the early treatment group compared to the standard treatment group. Considering time to treatment within a relatively early range of 1 hour or less, efficacy results when treating mild versus moderate pain were similar and both were associated with better outcomes than treatment of severe pain. When considering the prognostic variables of time to treatment and headache pain intensity (limited to moderate vs severe), both were independent predictors, with time to treatment a better predictor of headache duration and rescue medication use, and pain intensity a better predictor of 2-hour pain free and sustained pain free.
确定基于时间的早期治疗（不考虑疼痛强度）是否优于基于疼痛强度的治疗（即要求患者治疗至少中度强度的头痛），从而减少偏头痛的总体持续时间。
回顾性和前瞻性试验报告称，早期使用曲坦类药物或治疗轻度偏头痛疼痛时，治疗效果有所改善。然而，耐受性和疗效可能是阻碍这种新治疗模式被普遍接受的几个关键问题中的两个。
在这项多中心、开放标签、整群随机研究中，国际头痛协会（IHS）定义的偏头痛患者被指示使用12.5毫克阿莫曲坦治疗连续两次偏头痛发作，采用早期治疗（ET，即在头痛疼痛最早发作后1小时内治疗）或标准治疗（ST，即在头痛疼痛强度为中度或重度时治疗）。这种新颖的试验设计将偏头痛的总疼痛持续时间作为主要终点。
给出了首次头痛的结果，ITT人群包括757例ET患者和693例ST患者。与ST患者相比，ET患者的中位头痛持续时间（从头痛疼痛发作到无疼痛的时间）显著更短（3.18小时对5.53小时，P <.001）。对在发作后1小时内治疗头痛疼痛的ET亚组分析显示，疼痛强度，即治疗轻度或中度与重度疼痛，与由总头痛持续时间、2小时无痛、持续无痛和使用急救药物定义的治疗结果显著相关。对头痛发作后1小时内治疗与发作后1小时以上治疗的ST亚组进行多变量分析表明，疼痛强度，即治疗中度与重度头痛疼痛，以及早期与晚期治疗，均与总头痛持续时间、2小时无痛、持续无痛和使用急救药物显著相关。不良事件的总体发生率较低；恶心和头晕是两个治疗组中仅有的发生率≥1%的不良事件（恶心：ET组为2.5%，ST组为1.7%；头晕：ET组为1.1%，ST组为0.7%）。
与标准治疗组相比，早期治疗组的总头痛持续时间显著更短。考虑到在相对较早的1小时或更短时间内进行治疗，治疗轻度与中度疼痛时的疗效结果相似，且两者的治疗效果均优于治疗重度疼痛。当考虑治疗时间和头痛疼痛强度（限于中度与重度）的预后变量时，两者都是独立的预测因素，治疗时间对头痛持续时间和急救药物使用的预测性更好，而疼痛强度对2小时无痛和持续无痛的预测性更好。
