英夫利昔单抗治疗静脉用丙种球蛋白无反应型川崎病2例并文献分析

Infliximab treatment of intravenous immunoglobulin - resistant Kawasaki disease in 2 children and literature review

目的 探讨英夫利昔单抗治疗静脉用丙种球蛋白（IVIG）无反应型川崎病的疗效及应用前景。方法 总结2例北京大学第一医院收治的IVIG无反应型川崎病患儿的临床特征，以及其应用英夫利昔单抗后的临床表现、炎性指标及冠状动脉的动态变化。总结并分析近10年来该药用于 IVIG 无反应型川崎病患儿治疗的机制及应用进展。结果 北京大学第一医院收治的2例川崎病患儿均已应用2剂2 g/kgIVIG 治疗及甲泼尼龙冲击治疗，分别于体温正常后2 d及6 d，再次出现发热等川崎病急性期表现。2例患儿均予英夫利昔单抗（5 mg/kg）单剂静脉滴注，治疗即日体温正常，临床表现显著缓解。近10年中英夫利昔单抗应用于川崎病治疗的4篇基础研究文献及9篇回顾性或前瞻性的临床研究结果显示，英夫利昔单抗可有效缓解川崎病急性炎性反应水平，被越来越多地应用于治疗难治性川崎病，完全缓解率达72.73% ～92.11% ，治疗后患儿12 h内热退，临床症状体征显著改善，伴关节炎者关节痛消退。1例急性期合并肝炎的患儿在恢复期合并胆囊炎。将英夫利昔单抗应用于川崎病患儿的初始治疗方案已进入三期临床试验。结论 英夫利昔单抗可作为治疗IVIG无反应型川崎病患儿的备选药物，其安全性及有效性已得到证实，但目前尚属超说明书用药，其应用需签署知情同意，并获得伦理委员会批准。

Objective To investigate the clinical effect and the prospect of Infliximab in treatment of intrave- nous immunoglobulin （IVIG） - resistant Kawasaki disease （KD） patients. Methods Clinical features, inflammatory markers and coronary changes were observed in 2 cases of IVIG - resistant KD patients hospitalized in Peking Universi- ty First Hospital,who were treated effectively by Infliximab. Relevant researches on the mechanism and progress of the Infliximab treatment for IVIG - resistant KD in the last 10 years were reviewed at the same time. Results Two KD pa- tients hospitalized in Peking University First Hospital had been treated with 2 g/kg IVIG for 2 times and followed by methylprednisolone treatment. However,fever and other clinical manifestations occurred again after 2 days and 6 days when temperature returned normal. They both defervesced and all the symptoms were improved after 1 dose of Infliximab （5 mg/kg） by laboratory examinations. Four published literatures of the basic research and 9 retrospective or prospec- tive clinical researches of Infliximab treatment of KD showed that Infliximab alleviated the inflammatory level in the KD patients significantly. Complete remission was up to 72.73% -92.11%. Those KD patients defervesced within 12 h, with dramatic improvement of symptoms and signs. Arthralgia also disappeared in the patients with arthritis. Only 1 case was complicated with hepatitis in the acute phase and cholecystitis in recovery time. A phase 3 randomised, double - blinded,placebo - controlled trial had been done to assess the addition of Infliximab to the standard therapy. Conclusions Infliximab is a feasible choice for IVIG - resistant KD patients. Efficacy and safety of Infliximab for KD treatment have been proved in the literature. However, Infliximab for KD treatment has not been indicated in the drug instruction, so the informed consent from the guardians and Ethics Committee is needed.