Straburzyński Marcin, Kopyt Daria, Marschollek Karol, Błaszczyk Bartłomiej, Kuca-Warnawin Ewa, Kurowska Weronika, Misiak Błażej, Peng Kuan-Po, Waliszewska-Prosół Marta, May Arne
Department of Family Medicine and Infectious Diseases, University of Warmia and Mazury in Olsztyn, Warszawska 30, Olsztyn, 10-082, Poland.
Scientific Section of the Polish Society of Family Medicine, Syrokomli 1, Wroclaw, 51-141, Poland.
J Headache Pain. 2025 Apr 25;26(1):88. doi: 10.1186/s10194-025-02040-0.
Calcitonin gene related peptide (CGRP) pathway targeting therapies have proven efficacy, safety and tolerability. However, CGRP is also involved in immune responses, and reports of an increased risk of infection have emerged. This meta-analysis aims to verify whether CGRP-targeting therapies show evidence of increasing infection risk.
A systematic review was conducted according to PRISMA-Harms guidelines. A PubMed and Embase search result selection and extraction was performed. Risk of bias, sensitivity analysis, and fixed/random effects network meta-analyses were conducted for incidence of infectious adverse events in the studied populations with subsequent effect size assessment. An additional infectious serious adverse event search was performed in double-blind and open-label studies.
The search and selection process yielded 37 randomized placebo-controlled trials. 22,518 patients (77.3% women) treated with erenumab, fremanezumab, galcanezumab, eptinezumab, atogepant and rimegepant participated in these studies. Preventive CGRP-targeting therapies appear to increase the infection relative risk (RR = 1.08 [1.01; 1.14], p = 0.016, Number Needed to Harm [NNH] = 287). However, in individual analyses only galcanezumab and eptinezumab showed an increase in risk of infections: galcanezumab at clinically used doses (RR 1.13 [1.02; 1.25], p = 0.024, NNH = 77); eptinezumab at higher doses (RR 1.23 [1.04; 1.45], p = 0.015, NNH = 24). Fremanezumab was associated with fewest infectious SAEs (n = 3 in 3 studies), while erenumab showed the highest incidence of these events (n = 36 in 11 studies).
CGRP has multiple and often potentially opposing effects on the immune system. In effect, preventive CGRP pathway antagonists (especially eptinezumab and galcanezumab) possibly only mildly increase the risk of infections. However, it is unlikely to affect most migraine patients considering relatively high NNH, low effect size and few infectious SAEs reported so far. The result of CGRP-targeting therapies potentially depends on the type of pathogen and patient's immune status. Consequently, in immunocompromised patients or at public health levels the increased infection risk may have more pronounced effect.
降钙素基因相关肽（CGRP）通路靶向治疗已被证明具有疗效、安全性和耐受性。然而，CGRP也参与免疫反应，并且已经出现了感染风险增加的报道。这项荟萃分析旨在验证CGRP靶向治疗是否有证据表明会增加感染风险。
根据PRISMA-Harms指南进行系统评价。对PubMed和Embase的检索结果进行筛选和提取。对研究人群中感染性不良事件的发生率进行偏倚风险、敏感性分析以及固定/随机效应网络荟萃分析，并随后进行效应量评估。在双盲和开放标签研究中额外进行了感染性严重不良事件检索。
检索和筛选过程产生了37项随机安慰剂对照试验。22518名患者（77.3%为女性）接受了erenumab、fremanezumab、galcanezumab、eptinezumab、atogepant和rimegepant治疗并参与了这些研究。预防性CGRP靶向治疗似乎会增加感染相对风险（RR = 1.08 [1.01; 1.14]，p = 0.016，伤害所需人数[NNH] = 287）。然而，在个体分析中，只有galcanezumab和eptinezumab显示感染风险增加：临床使用剂量的galcanezumab（RR 1.13 [1.02; 1.25]，p = 0.024，NNH = 77）；较高剂量的eptinezumab（RR 1.23 [1.04; 1.45]，p = 0.015，NNH = 24）。Fremanezumab与最少的感染性严重不良事件相关（3项研究中有3例），而erenumab显示这些事件的发生率最高（11项研究中有36例）。
CGRP对免疫系统有多种且往往潜在相反的作用。实际上，预防性CGRP通路拮抗剂（尤其是eptinezumab和galcanezumab）可能只会轻微增加感染风险。然而，考虑到相对较高的NNH、较小的效应量以及目前报告的感染性严重不良事件较少，这不太可能影响大多数偏头痛患者。CGRP靶向治疗的结果可能取决于病原体类型和患者的免疫状态。因此，在免疫功能低下的患者中或在公共卫生层面，增加的感染风险可能会产生更明显的影响。
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