全身性重症肌无力患者补体C5抑制与生存率提高和心血管风险增加有关
Complement C5 inhibition in generalized myasthenia gravis is associated with improved survival and increased cardiovascular risk.
摘要(中文译文)
补体C5抑制剂是乙酰胆碱受体抗体阳性全身型重症肌无力（MG）的有效疾病修饰治疗药物，但其心血管安全性尚未作为专门的结果领域进行评估。随着使用范围扩大和用药时间延长，需要对心血管及血栓栓塞风险进行系统评估，包括不同C5抑制剂之间可能存在的差异。我们利用TriNetX联邦电子健康记录网络开展了一项回顾性队列研究，纳入成年全身型MG患者。通过倾向评分匹配的队列，比较接受C5抑制剂治疗的患者与未治疗对照（N=1,094对1,094），以及ravulizumab与eculizumab（N=330对330）。结局包括365天内的主要不良心血管事件（MACE）、血栓性疾病、急性肾损伤（AKI）、心律失常及全因死亡率。采用风险比（RR）和Cox比例风险模型评估相关性。匹配后，与未接受C5抑制治疗相比，C5抑制与AKI风险增加相关（6.1%对3.2%，p<0.01；RR 1.70）及血栓性疾病风险增加相关（5.1%对2.6%，p=0.002；RR 1.74）。接受C5治疗的患者一年后全因死亡率显著降低（RR 0.54；p=0.045）。C5抑制组MACE发生率更高（8.3%对5.5%；p=0.009），且随时间推移风险有升高趋势。在药物特异性分析中（ravulizumab对eculizumab），与eculizumab相比，ravulizumab与MACE风险显著降低相关（6.6%对11.1%，p=0.041；HR 0.58），而死亡率、血栓事件及其他心血管结局的风险相似。全身型MG中C5抑制与生存改善相关，但心血管及血栓栓塞风险增加。尽管受回顾性设计限制，本分析突显了一个具有临床意义的安全性信号，并提示C5抑制剂类别内存在异质性。随着补体抑制的应用不断扩大，对MG患者进行仔细的纵向心血管监测对临床医生将日益重要。
Abstract
Complement C5 inhibitors are effective disease-modifying therapies for acetylcholine receptor antibody-positive generalized myasthenia gravis (MG), but cardiovascular safety has not been evaluated as a dedicated outcome domain. With increasing and prolonged use, systematic assessment of cardiovascular and thromboembolic risk - including potential differences between individual C5 inhibitors - is needed. We performed a retrospective cohort study using the TriNetX federated electronic health record network, including adults with generalized MG. Propensity score-matched cohorts compared patients treated with C5 inhibitors with untreated controls (N = 1,094 vs. 1,094), and ravulizumab with eculizumab (N = 330 vs. 330). Outcomes included major adverse cardiovascular events (MACE), thrombotic disorders, acute kidney injury (AKI), arrhythmias, and all-cause mortality over 365 days. Associations were evaluated using risk ratios (RR) and Cox proportional hazards models. After matching, C5 inhibition was associated with increased risk of AKI (6.1% vs 3.2%, p<0.01; RR 1.70) and thrombotic disorders (5.1% vs 2.6%, p=0.002; RR 1.74) compared to no C5-inhibition treatment. All-cause mortality was significantly lower among C5-treated patients after one year (RR 0.54; p=0.045). MACE occurred more frequently with C5 inhibition (8.3% vs 5.5%; p=0.009), with a trend toward higher hazard over time. In agent-specific analyses (ravulizumab vs. eculizumab), ravulizumab was associated with a significantly lower hazard of MACE compared with eculizumab (6.6% vs 11.1%, p=0.041; HR 0.58, while hazards for mortality, thrombotic events, and other cardiovascular outcomes were similar. C5 inhibition in generalized MG is associated with improved survival but increased cardiovascular and thromboembolic risk. Although limited by its retrospective design, this analysis highlights a clinically relevant safety signal and suggests heterogeneity within the C5 inhibitor class. As use of complement inhibition expands, careful longitudinal cardiovascular monitoring will become increasingly important for clinicians managing patients with MG.
如何引用
AMA
Carl Vahldieck, Benedikt Fels. Complement C5 inhibition in generalized myasthenia gravis is associated with improved survival and increased cardiovascular risk.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1812643.
APA
Carl Vahldieck, Benedikt Fels (2026). Complement C5 inhibition in generalized myasthenia gravis is associated with improved survival and increased cardiovascular risk.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1812643
GB/T 7714
Carl Vahldieck, Benedikt Fels. Complement C5 inhibition in generalized myasthenia gravis is associated with improved survival and increased cardiovascular risk.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1812643.
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