Albert Einstein College of Medicine, Bronx, NY, USA.
Eli Lilly and Company, Corporate Center, Indianapolis, IN, 46285, USA.
J Headache Pain. 2021 Aug 28;22(1):101. doi: 10.1186/s10194-021-01303-w.
While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing.
Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom.
Patients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time.
This study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint.
SAMURAI ( NCT02439320 ); SPARTAN ( NCT02605174 ).
目前，治疗偏头痛急性发作的临床试验主要以 2 小时无疼痛为关键的主要疗效终点，但 2 小时时头痛程度与其他疗效指标之间的关系很少被探讨。在lasmiditan 治疗中重度头痛的偏头痛发作后，我们对比了那些在 2 小时后达到无痛的患者和那些仅达到轻度疼痛但未达到无痛的患者。
来自两项比较 lasmiditan 和安慰剂（SAMURAI 和 SPARTAN）的 3 期临床试验的患者水平数据被汇总到研究和治疗组中。这项事后分析评估了在 2 小时达到无痛的患者与 2 小时时仅达到轻度疼痛的患者相比，在最困扰症状（MBS）缓解、偏头痛相关功能障碍（残疾）缓解和患者总体印象变化（PGIC）改善方面的情况。轻度疼痛与疼痛缓解不同，后者定义为轻度疼痛或无痛。
与 2 小时轻度疼痛的患者（N=864）相比，在 2 小时达到无痛的患者（N=913）更有可能达到 MBS 缓解（91.9%比 44.9%）、残疾缓解（87.1%比 13.4%）和 PGIC 改善（86.5%比 31.5%）（所有组合的 p<0.001）。此外，更多无痛的患者同时达到 2 小时 MBS 缓解和 2 小时功能残疾缓解（83.6%），而仅有轻度疼痛的患者为 10.8%（p<0.001）。无痛的患者中，没有达到 MBS 或残疾缓解的患者比例（4.6%）低于轻度疼痛的患者（52.4%）。最后，在达到残疾缓解之前经历轻度疼痛的患者比例（55.2%）低于同时达到无痛和残疾缓解的患者（72.1%）。
这项研究表明，在治疗后 2 小时，与仅有轻度疼痛的患者相比，达到无痛的患者更有可能达到其他疗效终点，包括 MBS 缓解、偏头痛相关功能障碍缓解和 PGIC 改善，证实 2 小时无痛与其他临床结局的相关性强于 2 小时轻度疼痛终点。
SAMURAI（NCT02439320）；SPARTAN（NCT02605174）。
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