目的: 系统评价3种降钙素基因相关肽单克隆抗体(CGRP-mAbs)在真实世界研究和随机对照试验(RCT)中预防性治疗难治性偏头痛的有效性和安全性。方法: 计算机检索中国知网、万方、PubMed、Cochrane Library、Embase，收集关于CGRP-mAbs治疗难治性偏头痛的真实世界研究和RCT，检索时间为建库至 2022年 5月，提取资料后按 Cochrane 系统评价手册 5.1.0 提供的偏倚风险评估工具和改良的Jadad量表进行质量评价，采用 RevMan 5.1和Stata 14.0软件进行 Meta 分析。结果: 共纳入9项研究，共2 118例患者。Meta分析结果显示，RCT组的平均每月偏头痛天数的变化(MMD)(MD=-2.75，95%CI -3.67～-1.83，P<0.001)、平均每月偏头痛天数减少≥50%的患者比例(MMD50)(0.346，95%CI 0.309～0.383，P<0.001) 、平均每月急性偏头痛特异性用药天数的变化(MSAD)(MD=-2.53，95%CI -4.00～-1.06，P<0.001)均较基线有显著变化且均优于安慰剂；真实世界组MMD(MD=-6.30，95%CI-8.27～-4.34，P<0.001)、MMD50(0.427，95%CI 0.333～0.521,P<0.001)，MSAD(MD=-4.1，95%CI -4.9～-3.3，P<0.001)均较基线有显著变化。按照发作性偏头痛和慢性偏头痛进行亚组分析，结果显示，发作性偏头痛MMD(MD=-3.28，95%CI-3.92～-2.64， P<0.001)、慢性偏头痛MMD(MD=-5.04，95%CI-5.91～-4.16，P<0.001)，慢性偏头痛MMD高于发作性偏头痛(P<0.05)；发作性偏头痛MMD50[0.36(0.24～0.48)，P<0.001)、慢性偏头痛MMD50［0.33(0.27～0.40)，P<0.001]，慢性偏头痛MMD50少于发作性偏头痛(P<0.05)；发作性偏头痛MSAD(MD=-3.11，95%CI-4.61～-1.61，P<0.001)、慢性偏头痛MSAD(MD=-4.34，95%CI-6.06,-2.63，P<0.001)，慢性偏头痛MSAD高于发作性偏头痛(P<0.05)。真实世界组总不良反应发生率为0.321(95%CI 0.240～0.402，P<0.001)，RCT组的总不良反应发生率为0.509(95%CI 0.476～0.541，P<0.001)。结论: CGRP-mAbs治疗难治性偏头痛有显著效果，且不良反应率低。与发作性偏头痛的疗效比较，CGRP-mAbs更能有效减轻慢性偏头痛患者头痛发作和特异性用药天数。

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