BACKGROUND Galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days in phase 2 and 3 trials. In these analyses, we aimed to evaluate the safety and tolerability of galcanezumab compared with placebo for prevention of episodic or chronic migraine. METHODS Data were integrated from three double-blind clinical studies for the up to 6-month galcanezumab exposure group (N = 1435), and from five clinical studies for the up to 1-year all-galcanezumab exposure group (N = 2276). Patients received a monthly 120 mg subcutaneous injection of galcanezumab (with a 240 mg loading dose in month 1), 240 mg galcanezumab, or placebo. Outcomes measured were treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and discontinuation due to AEs (DCAEs). Laboratory results, vital signs, electrocardiogram (ECG), suicidal ideation and behavior results were evaluated. RESULTS TEAEs that occurred more frequently in galcanezumab-treated patients included injection site pain, injection site reactions excluding pain, constipation, vertigo, and pruritus. The proportion of DCAEs among galcanezumab-treated patients ranged between 1.8 and 3.0%, and differed from placebo group for galcanezumab 240 mg (P < 0.05). Fewer than 2.0% of patients in either galcanezumab dose-group compared with 1.0% of placebo-treated patients reported a SAE. There were no clinically meaningful differences between galcanezumab and placebo in laboratory measures, vital signs including blood pressure, ECGs, cardiovascular-related AEs, or suicidal ideation and behavior. CONCLUSIONS Galcanezumab demonstrated a favorable safety and tolerability profile for up to 1 year of treatment for the prevention of migraine. TRIAL REGISTRATION Clinical Trials CGAB = NCT02163993, EVOLVE-1 = NCT02614183, EVOLVE-2 = NCT02614196, REGAIN = NCT02614261, and CGAJ = NCT02614287. All were first posted on 25 November 2015, except CGAB posted on 16 June 2014, and before enrolling the first patient.

中文翻译：

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偏头痛患者每月加仑单抗的安全性和耐受性：偏头痛临床研究的综合结果。

背景技术Galcanezumab是一种选择性结合降钙素基因相关肽的人源化单克隆抗体，在2期和3期试验中已证明每月偏头痛头痛天数显着减少。在这些分析中，我们旨在评估galcanezumab与安慰剂相比在预防偶发性或慢性偏头痛中的安全性和耐受性。方法汇总了长达6个月的加那珠单抗暴露组（N = 1435）的三项双盲临床研究和长达1年的全部加那珠单抗暴露组（N = 2276）的五项临床研究的数据。患者每月接受120 mg皮下注射的galcanezumab（在第1个月中的剂量为240 mg），240 mg galcanezumab或安慰剂。评估的结果是治疗紧急不良事件（TEAE），严重AE（SAE），以及因不良事件（DCAE）而停产。评估实验室结果，生命体征，心电图（ECG），自杀意念和行为结果。结果在接受加那珠单抗治疗的患者中，TEAE发生频率更高，包括注射部位疼痛，注射部位反应（不包括疼痛，便秘，眩晕和瘙痒）。加尔珠单抗治疗的患者中DCAE的比例在1.8％至3.0％之间，并且与安慰剂组相比，加尔珠单抗240 mg差异较大（P <0.05）。两种加那珠单抗剂量组中只有不到2.0％的患者报告了SAE，而安慰剂治疗的患者中只有1.0％。galcanezumab和安慰剂之间在实验室指标，生命体征包括血压，ECG，心血管相关AE或自杀意念和行为方面在临床上没有有意义的差异。结论Galcanezumab在长达1年的偏头痛预防治疗中显示出良好的安全性和耐受性。试验注册临床试验CGAB = NCT02163993，EVOLVE-1 = NCT02614183，EVOLVE-2 = NCT02614196，REGAIN = NCT02614261和CGAJ = NCT02614287。除CGAB于2014年6月16日以及在招募第一位患者之前，所有信息均于2015年11月25日首次发布。