Background & Objective

To conduct a systematic review and network meta-analysis of all randomized trials investigating effects of anti-calcitonin gene related peptide monoclonal antibodies (anti-CGRP mAbs) on adult patients with chronic migraine.

Methods

MEDLINE, Embase and Cochrane Central Register of Controlled Trials searched from inception to July 2020; and clinical trial registries. The network meta-analysis was conducted in Bayesian framework using OpenBUGS and R, with the random effects model selected to allow for apparent heterogeneity between studies in the treatment comparison effects.

Results

Overall 38 studies (5164 chronic migraineurs in seven randomized trials) were included with treatment course of at least 12 weeks. Fremanezumab 675 + 225 + 225 mg QM (SC) injections were numerically more effective in lowering migraine days with lower MDs compared to eptinezumab 10 mg (IV) (MD: −1.52, 95% CrIs: −4.24, 0.99), eptinezumab 30 mg (IV) (MD: −0.33, 95% CrIs: −3.02, 2.16), eptinezumab 100 mg (IV) (MD: −0.59, 95% CrIs: −2.80, 1.42), eptinezumab 300 mg (IV) (MD: −0.02, 95% CrIs: −2.29, 1.98), erenumab 70 mg QM (SC) (MD: −0.17, 95% CrIs: −2.84, 2.25), erenumab 140 mg QM (SC) (MD: −0.18, 95% CrIs: −2.87, 2.26), fremanezumab 675 mg (SC) (MD: −0.30, 95% CrIs: −1.81, 1.14), galcanezumab 120 mg QM (SC) (MD: −0.71, 95% CrIs: −3.44, 1.55) and galcanezumab 240 mg QM (SC) (MD: −0.58, 95% CrIs: −3.09, 1.89), however the results were non-significant. Similarly, the anti-CGRP mAbs were also observed to have comparable safety and immunogenicity with no significant differences.

Conclusions

Although all doses of anti-CGRP mAbs have comparable efficacy, safety and tolerability based on uncertainties in indirect comparisons for all outcomes, the calculated effect estimates numerically favored high doses of subcutaneous fremanezumab and intravenous eptinezumab as the effective therapy with acceptable safety and tolerability for short term prevention of chronic migraine.

中文翻译：

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抗降钙素基因相关肽单克隆抗体治疗慢性偏头痛的疗效和安全性：系统评价和网络荟萃分析

背景与目的

对所有研究抗降钙素基因相关肽单克隆抗体 (anti-CGRP mAb) 对成年慢性偏头痛患者影响的随机试验进行系统回顾和网络荟萃分析。

方法

MEDLINE、Embase 和 Cochrane Central Register of Controlled Trials 从开始到 2020 年 7 月进行了检索；和临床试验登记处。使用 OpenBUGS 和 R 在贝叶斯框架中进行网络荟萃分析，选择随机效应模型以允许研究之间在治疗比较效应中存在明显的异质性。

结果

总共纳入了 38 项研究（7 项随机试验中的 5164 名慢性偏头痛患者），疗程至少为 12 周。与 eptinezumab 10 mg (IV) (MD: -1.52, 95% CrIs: -4.24, 0.99), eptinezumab 30 mg 相比，Fremanezumab 675 + 225 + 225 mg QM (SC) 注射在降低偏头痛天数方面更有效，MDs 较低(IV) (MD: -0.33, 95% CrIs: -3.02, 2.16), eptinezumab 100 mg (IV) (MD: -0.59, 95% CrIs: -2.80, 1.42), eptinezumab 300 mg (IV) (MD: -0.02, 95% CrIs: -2.29, 1.98), erenumab 70 mg QM (SC) (MD: -0.17, 95% CrIs: -2.84, 2.25), erenumab 140 mg QM (SC) (MD: -0.18, 95) % CrIs：-2.87, 2.26)，fremanezumab 675 mg (SC) (MD: -0.30, 95% CrIs: -1.81, 1.14)，galcanezumab 120 mg QM (SC) (MD: -0.71, 95% CrIs: -3.44) , 1.55) 和 galcanezumab 240 mg QM (SC) (MD: -0.58, 95% CrIs: -3.09, 1.89)，但结果不显着。

结论

尽管基于所有结果的间接比较的不确定性，所有剂量的抗 CGRP mAb 都具有相当的疗效、安全性和耐受性，但计算出的效果估计值在数值上支持高剂量皮下 fremanezumab 和静脉内依替尼单抗作为有效治疗，短期内具有可接受的安全性和耐受性长期预防慢性偏头痛。