Eli Lilly and Company, Indianapolis, IN, USA.
Institute of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil.
Postgrad Med. 2021 May;133(4):449-459. doi: 10.1080/00325481.2020.1860619. Epub 2021 Mar 17.
: Lasmiditan is a selective serotonin (1F) receptor agonist approved for acute treatment of migraine with 3 doses: 50, 100, and 200 mg.: 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.: 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.: 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.: 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).
拉米替坦是一种选择性 5-羟色胺（5-HT1F）受体激动剂，已获批用于偏头痛的急性治疗，有 3 种剂量：50、100 和 200 毫克。为了帮助提供剂量方面的见解，我们评估了拉米替坦在以相同或不同剂量治疗两次偏头痛发作的患者中的疗效和安全性。综合分析使用了来自两项对照、3 期单攻击研究（SAMURAI/SPARTAN）中任一一次偏头痛发作治疗和开放标签 GLADIATOR 扩展研究中首次发作后治疗的数据。根据在 SAMURAI 或 SPARTAN 中首次接受的剂量和 GLADIATOR 中随后的剂量，创建了 8 个患者组：安慰剂-100、安慰剂-200、50-100、50-200、100-100、100-200、200-100、200-200。在给药后 2 小时评估偏头痛疼痛缓解、偏头痛相关功能障碍缓解、最困扰症状（MBS）缓解和疼痛缓解。评估最常见的治疗相关不良事件（MC-TEAE）的发生情况。对疼痛缓解和≥1 个 MC-TEAE 进行了转移分析。使用 McNemar 检验比较了每个剂量变化组中首次和随后剂量的特定结局患者的发生率。当第二次拉米替坦剂量高于初始剂量时，疼痛缓解、偏头痛相关功能障碍缓解、MBS 缓解和疼痛缓解的发生率略有增加。对于起始剂量为 50 毫克的患者，增加至 100 毫克或 200 毫克可提供积极的疗效-TEAE 平衡，尽管≥1 个 MC-TEAE 的发生率增加。对于起始剂量为 100 毫克的患者，增加至 200 毫克可提供积极的疗效-TEAE 平衡。如果初始剂量为 100 毫克或 200 毫克，随后剂量的患者经历≥1 个 MC-TEAE 的发生率下降或保持不变，无论剂量如何。从 200 毫克减少至 100 毫克可导致疼痛缓解和≥1 个 MC-TEAE 的患者减少，从而导致疗效-TEAE 平衡中性。转移分析支持这些发现。对于增加拉米替坦剂量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很重要。临床试验.gov：SAMURAI（NCT02439320）；SPARTAN（NCT02605174）；GLADIATOR（NCT02565186）。
