Corporate Center, Eli Lilly and Company, Indianapolis, IN, USA.
Curr Med Res Opin. 2020 Nov;36(11):1791-1806. doi: 10.1080/03007995.2020.1808780. Epub 2020 Oct 6.
Determine whether common migraine comorbidities affect the efficacy and safety of lasmiditan, a 5-HT receptor agonist approved in the United States for the acute treatment of migraine.
In SPARTAN and SAMURAI (double-blind Phase 3 clinical trials), patients with migraine were randomized to oral lasmiditan 50 mg (SPARTAN only), 100mg, 200 mg, or placebo. Lasmiditan increased the proportion of pain-free and most bothersome symptom (MBS)-free patients at 2 h after dose compared with placebo. Most common treatment-emergent adverse events (TEAEs) were dizziness, paraesthesia, somnolence, fatigue, nausea, muscular weakness, and hypoesthesia. Based upon literature review of common migraine comorbidities, Anxiety, Allergy, Bronchial, Cardiac, Depression, Fatigue, Gastrointestinal, Hormonal, Musculoskeletal/Pain, Neurological, Obesity, Sleep, and Vascular Comorbidity Groups were created. Using pooled results, efficacy and TEAEs were assessed to compare patients with or without a given common migraine comorbidity. To compare treatment groups, -values were calculated for treatment-by-subgroup interaction, based on logistic regression with treatment-by-comorbidity condition status (Yes/No) as the interaction term; study, treatment group, and comorbidity condition status (Yes/No) were covariates. Differential treatment effect based upon comorbidity status was also examined. Trial registration at clinicaltrials.gov: SAMURAI (NCT02439320) and SPARTAN (NCT02605174).
Across all the Comorbidity Groups, with the potential exception of fatigue, treatment-by-subgroup interaction analyses did not provide evidence of a lasmiditan-driven lasmiditan versus placebo differential treatment effect dependent on Yes versus No comorbidity subgroup for either efficacy or TEAE assessments.
The efficacy and safety of lasmiditan for treatment of individual migraine attacks appear to be independent of comorbid conditions.
确定常见偏头痛合并症是否会影响拉米替坦（一种在美国被批准用于治疗偏头痛急性发作的 5-HT 受体激动剂）的疗效和安全性。
在 SPARTAN 和 SAMURAI（双盲 3 期临床试验）中，偏头痛患者被随机分配接受口服拉米替坦 50mg（仅 SPARTAN）、100mg、200mg 或安慰剂。与安慰剂相比，拉米替坦在给药后 2 小时增加了无疼痛和最困扰症状（MBS）无的患者比例。最常见的治疗后出现的不良事件（TEAE）是头晕、感觉异常、嗜睡、疲劳、恶心、肌肉无力和感觉减退。基于对常见偏头痛合并症的文献回顾，创建了焦虑、过敏、支气管、心脏、抑郁、疲劳、胃肠道、激素、肌肉骨骼/疼痛、神经、肥胖、睡眠和血管合并症组。使用汇总结果，评估疗效和 TEAEs，以比较具有或不具有特定常见偏头痛合并症的患者。为了比较治疗组，根据具有治疗-合并症状态（是/否）作为交互项的逻辑回归，计算了治疗-亚组交互作用的 -值；研究、治疗组和合并症状态（是/否）是协变量。还检查了基于合并症状态的治疗效果差异。在 clinicaltrials.gov 上进行了试验注册：SAMURAI（NCT02439320）和 SPARTAN（NCT02605174）。
在所有合并症组中，除了疲劳组之外，治疗-亚组交互作用分析并未提供证据表明拉米替坦与安慰剂相比，疗效或 TEAE 评估中，Yes 与 No 合并症亚组之间存在依赖于合并症的拉米替坦治疗效果差异。
拉米替坦治疗个体偏头痛发作的疗效和安全性似乎与合并症无关。
