Kodounis Michalis, Constantinidis Theodoros S, Rizonaki Konstantina, Drakou Eleni, Zintzaras Elias, Stefanidis Ioannis, Mitsikostas Dimos-Dimitrios, Dardiotis Efthimios
First Neurology Department, Eginitio Hospital, School of Medicine, National & Kapodistrian University of Athens, Athens, GRC.
Department of Biomathematics, University of Thessaly School of Medicine, Larissa, GRC.
Cureus. 2024 Jun 16;16(6):e62458. doi: 10.7759/cureus.62458. eCollection 2024 Jun.
Chronic migraine (CM) imposes significant personal, societal, and financial burdens, historically lacking specific prophylactic treatments. Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) represent a novel, mechanism-based, and migraine-specific prophylactic approach. Four mAbs, namely, erenumab, fremanezumab, galcanezumab, and eptinezumab, have been marketed, although head-to-head trials with standard anti-migraine treatments are absent. This study aimed to compare the efficacy and safety of anti-CGRP mAbs with standard anti-migraine treatments using a cross-trial indirect model of the absolute risk difference (ARD) of a 50% responder rate, in order to express the final results in terms of the number needed to treat (NNT) and number needed to harm (NNH). Phase 3 and 2b randomized controlled trials (RCTs) for CM prophylaxis were searched in the MEDLINE and CENTRAL databases with specific inclusion and exclusion criteria. The ARD between groups for the percentage of trial participants who reported a 50% reduction in monthly migraine days and the differences in the number of adverse events (AEs), serious adverse events (SAEs), and participants who withdrew from each RCT were calculated, and subsequently, the NNT and NNH were calculated for each one of the outcome measures. In total, eight RCTs were considered eligible. A similar efficacy and safety have been demonstrated among CGRP mAbs and all standard CM treatments. The results of the ARD for the total number of studies concerning efficacy, total adverse events, serious adverse events, and dropout from the RCTs ranged from -0.688 (95% confidence interval (CI): -0.821-(-0.513)) to -0.018 (95% CI: -0.044-(0.007)), from 0.032 (95% CI: -0.041, 0.104) to -0.380 (95% CI: -0.589, -0.126), from -0.025 (95% CI: -0.046, -0.006) to 0.014 (95% CI: -0.015, 0.42), from 0.048 (95% CI: -0.112, 0.014) to 0.232 (95% CI: -0.016, 0.458) correspondingly. All anti-CGRP mAbs showed a roughly equal statistically significant ARD and similar NNTs, ranging from 5 to 8, while the ARD of onbotulinum toxin A (oBTA) was not significant with an NNT 56. The two studies of topiramate showed contradictory results, the one significant while the other not, with NNTs 2 and 22, respectively. All four anti-CGRP mAbs showed an invariably high efficacy among their studies, in terms of the ARD and its derivative measure of NNT, in contrast to oBTA, while in topiramate, the results are contradictory between the two studies.
慢性偏头痛（CM）给个人、社会和经济带来了沉重负担，以往一直缺乏特效预防性治疗方法。靶向降钙素基因相关肽（CGRP）的单克隆抗体（mAb）代表了一种新型的、基于机制的偏头痛特异性预防方法。尽管缺乏与标准抗偏头痛治疗的头对头试验，但已有四种单克隆抗体，即erenumab、fremanezumab、galcanezumab和eptinezumab上市。本研究旨在使用50%缓解率的绝对风险差异（ARD）的交叉试验间接模型，比较抗CGRP单克隆抗体与标准抗偏头痛治疗的疗效和安全性，以便用治疗所需人数（NNT）和伤害所需人数（NNH）来表达最终结果。按照特定的纳入和排除标准，在MEDLINE和CENTRAL数据库中检索用于CM预防的3期和2b期随机对照试验（RCT）。计算报告每月偏头痛天数减少50%的试验参与者百分比的组间ARD，以及各RCT中不良事件（AE）、严重不良事件（SAE）的数量差异和退出试验的参与者数量差异，随后，针对每个结局指标计算NNT和NNH。总共八项RCT被认为符合条件。CGRP单克隆抗体和所有标准CM治疗方法的疗效和安全性相似。关于疗效、总不良事件、严重不良事件和RCT退出情况的所有研究的总ARD结果范围从-0.688（95%置信区间（CI）：-0.821-（-0.513））到-0.018（95%CI：-0.044-（0.007）），总不良事件的ARD范围从0.032（95%CI：-0.041，0.104）到-0.380（95%CI：-0.589，-0.126），严重不良事件的ARD范围从-0.025（95%CI：-0.046，-0.006）到0.014（95%CI：-0.015，0.42），RCT退出情况的ARD范围从0.048（95%CI：-0.112，0.014）到0.232（95%CI：-0.016，0.458）。所有抗CGRP单克隆抗体显示出大致相等的具有统计学意义的ARD和相似的NNT，范围为5至8，而A型肉毒毒素（oBTA）的ARD不显著，NNT为56。托吡酯的两项研究结果相互矛盾，一项有显著意义，另一项无显著意义，NNT分别为2和22。与oBTA相比，所有四种抗CGRP单克隆抗体在其研究中就ARD及其衍生指标NNT而言均显示出始终较高的疗效，而在托吡酯方面，两项研究结果相互矛盾。
