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目前关于 TNF-α 单克隆抗体英夫利昔单抗治疗川崎病的知识:全面综述。

Current knowledge of TNF-α monoclonal antibody infliximab in treating Kawasaki disease: a comprehensive review.

机构信息

Department of Pediatrics, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.

Department of Nephrology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, China.

出版信息

Front Immunol. 2023 Oct 23;14:1237670. doi: 10.3389/fimmu.2023.1237670. eCollection 2023.

Abstract

Kawasaki disease (KD), an autoinflammatory disease primarily affecting young children, characterized by consisting of acute systemic vasculitis and coronary artery involvement in severe cases. Intravenous immunoglobulin gamma (IVIG) combined with aspirin therapy is the first-line regimen for the prevention of coronary aneurysms in the acute phase of KD. The etiology and pathogenesis of KD are unclear, but its incidence is increasing gradually, especially in the cases of IVIG-naïve KD and refractory KD. Conventional therapies for refractory KD have unsatisfactory results. At present, infliximab (IFX), a human-murine chimeric monoclonal antibody that specifically blocks tumor necrosis factor-α (TNF-α), has made great progress in the treatment of KD. This review revealed that IFX infusion (5 mg/kg) could effectively modulate fever, reduce inflammation, improve arthritis, diminish the number of plasma exchange, decrease hospitalizations, and prevent the progression of coronary artery lesions. The adverse effects of IFX administration included skin rash, arthritis, respiratory disease, infusion reaction, hepatomegaly, and vaccination-associated complications. But the incidence of these adverse effects is low. The clear optimal application protocol of the application of IFX for either initial combination therapy or salvage therapy in KD is still under investigation. In addition, there are no effective biomarkers to predict IFX resistance. Further multicenter trials with large sample size and long-term follow-up are still needed to validate the clinical efficacy and safety of IFX for IVIG-resistant KD or refractory KD.

摘要

川崎病(KD)是一种主要影响儿童的自身炎症性疾病,其特征为急性全身性血管炎和严重病例的冠状动脉受累。静脉注射免疫球蛋白γ(IVIG)联合阿司匹林治疗是预防 KD 急性期冠状动脉瘤的一线方案。KD 的病因和发病机制尚不清楚,但发病率逐渐增加,尤其是在 IVIG 初治 KD 和难治性 KD 中。难治性 KD 的常规治疗效果不佳。目前,英夫利昔单抗(IFX)是一种人鼠嵌合单克隆抗体,可特异性阻断肿瘤坏死因子-α(TNF-α),在 KD 的治疗中取得了很大进展。综述表明,IFX 输注(5mg/kg)可有效调节发热,减轻炎症,改善关节炎,减少血浆置换次数,减少住院时间,并预防冠状动脉病变进展。IFX 给药的不良反应包括皮疹、关节炎、呼吸道疾病、输注反应、肝肿大和与疫苗接种相关的并发症。但这些不良反应的发生率较低。IFX 在 KD 中作为初始联合治疗或挽救治疗的应用的最佳应用方案仍在研究中。此外,目前还没有有效的生物标志物来预测 IFX 耐药性。仍需要进一步进行多中心、大样本量和长期随访的临床试验,以验证 IFX 对 IVIG 耐药性或难治性 KD 的临床疗效和安全性。

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