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Abstract：
Background: Lasmiditan is a selective serotonin (1F) receptor agonist approved for acute treatment of migraine with 3 doses: 50, 100, and 200 mg.Objective: To help provide dosing insights, we assessed the efficacy and safety of lasmiditan in patients who treated two migraine attacks with the same or different lasmiditan doses.Methods: Integrated analyses used data from the migraine attack treated in either of two controlled, Phase 3, single attack studies (SAMURAI/SPARTAN), and after the first attack treated in the open-label GLADIATOR extension study. Eight patient groups were created based on the initial dose received in SAMURAI or SPARTAN and the subsequent dose in GLADIATOR: placebo-100, placebo-200, 50-100, 50-200, 100-100, 100-200, 200-100, 200-200. Migraine pain freedom, migraine-related functional disability freedom, most bothersome symptom (MBS) freedom, and pain relief were evaluated at 2-h post-dose. The occurrence of most common treatment-emergent adverse events (MC-TEAE) was evaluated. Shift analyses were performed for pain freedom and ≥1 MC-TEAE. The incidence of patients with a specific outcome from the first and subsequent doses were compared within each dose change group using McNemar\'s test.Results: Small, but consistent, increases in incidences of pain freedom, migraine-related functional disability freedom, MBS freedom, and pain relief occurred when the second lasmiditan dose was higher than the initial dose. For patients starting on 50 mg, increasing to 100 or 200 mg provided a positive efficacy-TEAE balance, despite an increase in incidence of ≥1 MC-TEAE. For patients starting on 100 mg, increasing to 200 mg provided a positive efficacy-TEAE balance. If the initial dose was 100 or 200 mg, the incidence of patients experiencing ≥1 MC-TEAE decreased or stayed the same with their subsequent dose, regardless of dose. Decreasing from 200 to 100 mg led to a decrease in patients with pain freedom and ≥1 MC-TEAE, resulting in a neutral efficacy-TEAE balance. Shift analyses supported these findings.Conclusion: A positive efficacy-TEAE balance exists for patients increasing their lasmiditan dose for treatment of a subsequent migraine attack. These results could be important for optimizing dosing for individual patients.Clinicaltrials.gov: SAMURAI (NCT02439320); SPARTAN (NCT02605174); GLADIATOR (NCT02565186).
摘要：
背景：Lasmiditan是一种选择性5-羟色胺（1F）受体激动剂，被批准用于偏头痛的急性治疗，剂量为50、100和200mg。目标：为了帮助提供剂量见解，我们评估了lasmiditan在使用相同或不同剂量的2次偏头痛发作患者中的疗效和安全性.方法：综合分析使用两种对照中任何一种治疗偏头痛发作的数据，第3阶段，单次攻击研究（武警/斯巴坦），以及在开放标签GLADIATOR扩展研究中治疗的第一次发作之后。根据在SAMURAI或SPARTAN中接受的初始剂量和在GLADIATOR中接受的后续剂量，创建了八个患者组：安慰剂100，安慰剂200，50-100，50-200，100-100，100-200，200-100，200-200。偏头痛疼痛自由，偏头痛相关的功能性残疾自由，最麻烦的症状（MBS）自由，并在给药后2小时评估疼痛缓解情况。评估了最常见的因治疗引起的不良事件（MC-TEAE）的发生率。对疼痛自由度和≥1个MC-TEAE进行移位分析。使用McNemar检验，在每个剂量变化组中比较首次和后续剂量具有特定结果的患者的发生率。结果：小，但始终如一，疼痛自由的发生率增加，偏头痛相关的功能性残疾自由，MBS自由,当第二次lasmiditan剂量高于初始剂量时，疼痛缓解。对于开始服用50毫克的患者，增加到100或200毫克提供了积极的疗效-TEAE平衡，尽管≥1MC-TEAE的发生率增加。对于100毫克开始的患者，增加到200毫克提供了积极的疗效-TEAE平衡。如果初始剂量是100或200毫克，经历≥1MC-TEAE的患者的发生率降低或与随后的剂量保持相同，不管剂量。从200mg减少到100mg导致疼痛自由度和≥1MC-TEAE的患者减少，导致中性功效-TEAE平衡。班次分析支持这些发现。结论：对于增加其lasmiditan剂量以治疗随后的偏头痛发作的患者，存在积极的疗效-TEAE平衡。这些结果对于优化个体患者的剂量可能是重要的。Clinicaltrials.gov：SAMURAI（NCT02439320）；SPARTAN（NCT02605174）；GLADIATOR（NCT02565186）。
