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：经静脉给予ALD403预防偏头痛的安全性与有效性研究2（PROMISE-2）为一项Ⅲ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至接受静脉（intravenous, IV）依瑞奈尤单抗100mg、依瑞奈尤单抗300mg或安慰剂，于第0天及第12周给药。主要终点为第1~12周期间平均每月偏头痛天数（mean monthly migraine days, MMDs）较基线的变化值。
研究结果：纳入治疗的受试者共1072例，各组基线平均每月偏头痛天数约为16.1天。与安慰剂组相比，依瑞奈尤单抗100mg与300mg组在第1~12周期间的平均每月偏头痛天数均有显著降低（安慰剂组较基线减少5.6天，100mg组较基线减少7.7天，与安慰剂组相比p<0.0001；300mg组较基线减少8.2天，与安慰剂组相比p<0.0001）。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治疗组中发生率超过2%、且较安慰剂组发生率更高的治疗期间出现的不良事件：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，经静脉给药后的次日至第12周期间，依瑞奈尤单抗100mg与300mg均可显著降低平均每月偏头痛天数，且耐受性良好，安全性特征可接受。