Supplemental material for: PROMISE-2: Efficacy and safety of eptinezumab in patients with chronic migraine

Objective: To evaluate the efficacy and safety of eptinezumab, a humanized
anti–calcitonin gene-related peptide monoclonal antibody, in the
preventive treatment of chronic migraine (CM). Methods: The PRevention Of
Migraine via Intravenous ALD403 Safety and Efficacy–2 (PROMISE-2) study
was a phase 3, multicenter, randomized, double-blind, placebo-controlled,
parallel-group study. Adults with CM were randomly assigned to receive
intravenous (IV) eptinezumab 100 mg, eptinezumab 300 mg, or placebo,
administered on day 0 and week 12. The primary endpoint was change from
baseline in mean monthly migraine days (MMDs) over weeks 1–12. Results:
Among treated participants (n = 1072), baseline mean MMDs was ~16.1 across
groups. Treatment with eptinezumab 100 mg and 300 mg was associated with
significant reductions in MMDs across weeks 1–12 compared with placebo
(placebo, −5.6, 100 mg, −7.7, p < 0.0001 vs placebo; 300 mg, −8.2,
p < 0.0001 vs placebo). Treatment-emergent adverse events (TEAEs)
were reported by 43.5% (100 mg), 52.0% (300 mg), and 46.7% (placebo) of
patients. Nasopharyngitis was the only TEAE reported for >2% of
eptinezumab treated patients at an incidence of greater than 2% over
placebo; it occurred in the 300 mg eptinezumab arm (eptinezumab 9.4%,
placebo 6.0%). Conclusion: In patients with CM, eptinezumab 100 mg and 300
mg was associated with a significant reduction in MMDs from the day
following IV administration through week 12, was well tolerated, and
demonstrated an acceptable safety profile.

研究目的：评估依瑞奈尤单抗（eptinezumab）——一种人源化抗降钙素基因相关肽单克隆抗体，用于慢性偏头痛（chronic migraine, CM）预防性治疗的有效性与安全性。研究方法：此项名为经静脉输注ALD403预防偏头痛的安全性与有效性-2（PROMISE-2）的3期多中心随机双盲安慰剂对照平行组临床试验，将慢性偏头痛成人患者随机分配接受静脉输注（intravenous, IV）依瑞奈尤单抗100mg、依瑞奈尤单抗300mg或安慰剂，给药时机为第0天及第12周。本研究的主要终点为第1至12周的平均每月偏头痛天数（mean monthly migraine days, MMDs）相较于基线的变化值。研究结果：纳入分析的受试患者共1072例，各组基线平均每月偏头痛天数约为16.1天。相较于安慰剂组，依瑞奈尤单抗100mg组与300mg组在第1至12周的平均每月偏头痛天数均出现显著降低（安慰剂组较基线减少5.6天，100mg组减少7.7天，p<0.0001 vs 安慰剂组；300mg组减少8.2天，p<0.0001 vs 安慰剂组）。治疗期间出现的不良事件（treatment-emergent adverse events, TEAEs）发生率分别为：100mg组43.5%、300mg组52.0%、安慰剂组46.7%。鼻咽炎是唯一在依瑞奈尤单抗给药患者中发生率高于安慰剂组且超过2%的不良事件：在300mg依瑞奈尤单抗组中发生率为9.4%，安慰剂组为6.0%。研究结论：对于慢性偏头痛患者，依瑞奈尤单抗100mg与300mg给药方案可显著降低患者的平均每月偏头痛天数，起效时间为静脉给药次日起至第12周，且耐受性良好，安全性可接受。