Abstract：
OBJECTIVE: To compare calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) versus nonspecific oral migraine preventives (NOEPs).
BACKGROUND: Insurers mandate step therapy with NOEPs before approving CGRP mAbs.
METHODS: Databases were searched for class I or II randomized controlled trials (RCTs) comparing CGRP mAbs or NOEPs versus placebo for migraine prevention in adults. The primary outcome measure was monthly migraine days (MMD) or moderate to severe headache days.
RESULTS: Twelve RCTs for CGRP mAbs, 5 RCTs for topiramate, and 3 RCTs for divalproex were included in the meta-analysis. There was high certainty that CGRP mAbs are more effective than placebo, with weighted mean difference (WMD; 95% confidence interval) of -1.64 (-1.99 to -1.28) MMD, which is compatible with small effect size (Cohen\'s d -0.25 [-0.34 to -0.16]). Certainty of evidence that topiramate or divalproex is more effective than placebo was very low and low, respectively (WMD -1.45 [-1.52 to -1.38] and -1.65 [-2.30 to -1.00], respectively; Cohen\'s d -1.25 [-2.47 to -0.03] and -0.48 [-0.67 to -0.29], respectively). Trial sequential analysis showed that information size was adequate and that CGRP mAbs had clear benefit versus placebo. Network meta-analysis showed no statistically significant difference between CGRP mAbs and topiramate (WMD -0.19 [-0.56 to 0.17]) or divalproex (0.01 [-0.73 to 0.75]). No significant difference was seen between topiramate or divalproex (0.21 [-0.45 to 0.86]).
CONCLUSIONS: There is high certainty that CGRP mAbs are more effective than placebo, but the effect size is small. When feasible, CGRP mAbs may be prescribed as first-line preventives; topiramate or divalproex could be as effective but are less well tolerated. The findings of this study support the recently published 2024 position of the American Headache Society on the use of CGRP mAbs as the first-line treatment.
BACKGROUND: Insurers mandate step therapy with NOEPs before approving CGRP mAbs.
METHODS: Databases were searched for class I or II randomized controlled trials (RCTs) comparing CGRP mAbs or NOEPs versus placebo for migraine prevention in adults. The primary outcome measure was monthly migraine days (MMD) or moderate to severe headache days.
RESULTS: Twelve RCTs for CGRP mAbs, 5 RCTs for topiramate, and 3 RCTs for divalproex were included in the meta-analysis. There was high certainty that CGRP mAbs are more effective than placebo, with weighted mean difference (WMD; 95% confidence interval) of -1.64 (-1.99 to -1.28) MMD, which is compatible with small effect size (Cohen\'s d -0.25 [-0.34 to -0.16]). Certainty of evidence that topiramate or divalproex is more effective than placebo was very low and low, respectively (WMD -1.45 [-1.52 to -1.38] and -1.65 [-2.30 to -1.00], respectively; Cohen\'s d -1.25 [-2.47 to -0.03] and -0.48 [-0.67 to -0.29], respectively). Trial sequential analysis showed that information size was adequate and that CGRP mAbs had clear benefit versus placebo. Network meta-analysis showed no statistically significant difference between CGRP mAbs and topiramate (WMD -0.19 [-0.56 to 0.17]) or divalproex (0.01 [-0.73 to 0.75]). No significant difference was seen between topiramate or divalproex (0.21 [-0.45 to 0.86]).
CONCLUSIONS: There is high certainty that CGRP mAbs are more effective than placebo, but the effect size is small. When feasible, CGRP mAbs may be prescribed as first-line preventives; topiramate or divalproex could be as effective but are less well tolerated. The findings of this study support the recently published 2024 position of the American Headache Society on the use of CGRP mAbs as the first-line treatment.
摘要：
目的：比较降钙素基因相关肽单克隆抗体（CGRPmAb）与非特异性口服偏头痛预防药物（NOEP）。
背景：保险公司在批准CGRPmAb之前，必须使用NOEP进行阶梯治疗。
方法：在数据库中搜索I类或II类随机对照试验（RCTs），比较CGRPmAb或NOEP与安慰剂预防成人偏头痛的作用。主要结果指标是每月偏头痛天数（MMD）或中度至重度头痛天数。
结果：CGRP单克隆抗体的12个RCT，5托吡酯的随机对照试验，和3个双丙戊酸钠的RCT纳入荟萃分析。有很高的确定性，CGRP单克隆抗体比安慰剂更有效，加权平均差(WMD；95%置信区间)为-1.64(-1.99至-1.28)MMD，这与小效应大小(科恩的d-0.25[-0.34至-0.16])兼容。托吡酯或双丙戊酸钠比安慰剂更有效的证据的确定性非常低，(WMD分别为-1.45[-1.52至-1.38]和-1.65[-2.30至-1.00]，分别；科恩的d-1.25[-2.47至-0.03]和-0.48[-0.67至-0.29]，分别)。试验序贯分析表明，信息大小足够，CGRPmAb与安慰剂相比具有明显的益处。网络荟萃分析显示CGRPmAb与托吡酯(WMD-0.19[-0.56,0.17])或二丙戊酸钠(0.01[-0.73,0.75])之间无统计学差异。托吡酯或双丙戊酸钠之间没有显著差异(0.21[-0.45至0.86])。
结论：有很高的确定性，CGRP单克隆抗体比安慰剂更有效，但效果大小小。在可行的情况下,CGRP单克隆抗体可作为一线预防药物；托吡酯或双丙戊酸钠可能同样有效，但耐受性较差。这项研究的结果支持了美国头痛协会最近发表的2024年关于使用CGRPmAb作为一线治疗的立场。
背景：保险公司在批准CGRPmAb之前，必须使用NOEP进行阶梯治疗。
方法：在数据库中搜索I类或II类随机对照试验（RCTs），比较CGRPmAb或NOEP与安慰剂预防成人偏头痛的作用。主要结果指标是每月偏头痛天数（MMD）或中度至重度头痛天数。
结果：CGRP单克隆抗体的12个RCT，5托吡酯的随机对照试验，和3个双丙戊酸钠的RCT纳入荟萃分析。有很高的确定性，CGRP单克隆抗体比安慰剂更有效，加权平均差(WMD；95%置信区间)为-1.64(-1.99至-1.28)MMD，这与小效应大小(科恩的d-0.25[-0.34至-0.16])兼容。托吡酯或双丙戊酸钠比安慰剂更有效的证据的确定性非常低，(WMD分别为-1.45[-1.52至-1.38]和-1.65[-2.30至-1.00]，分别；科恩的d-1.25[-2.47至-0.03]和-0.48[-0.67至-0.29]，分别)。试验序贯分析表明，信息大小足够，CGRPmAb与安慰剂相比具有明显的益处。网络荟萃分析显示CGRPmAb与托吡酯(WMD-0.19[-0.56,0.17])或二丙戊酸钠(0.01[-0.73,0.75])之间无统计学差异。托吡酯或双丙戊酸钠之间没有显著差异(0.21[-0.45至0.86])。
结论：有很高的确定性，CGRP单克隆抗体比安慰剂更有效，但效果大小小。在可行的情况下,CGRP单克隆抗体可作为一线预防药物；托吡酯或双丙戊酸钠可能同样有效，但耐受性较差。这项研究的结果支持了美国头痛协会最近发表的2024年关于使用CGRPmAb作为一线治疗的立场。
