Ebata Ryota, Yasukawa Kumi, Nagai Kazue, Saito Yuko, Higashi Kouji, Homma Jun, Takada Nobuyuki, Takechi Fumie, Saito Naoki, Kobayashi Hironobu, Okunushi Kentaro, Hamada Hiromichi, Kohno Yoichi, Hanaoka Hideki, Shimojo Naoki
Department of Pediatrics, Graduate School of Medicine, Chiba University, Yachiyo, Japan.
Clinical Research Center, Chiba University Hospital, Chiba, Japan.
Pediatr Int. 2019 May;61(5):438-443. doi: 10.1111/ped.13851. Epub 2019 May 17.
There is still no definite treatment for refractory Kawasaki disease (KD). In this pilot study, we evaluated the safety and efficacy of a new protocol consisting of sivelestat sodium hydrate (SSH) combined with additional i.v. immunoglobulin (IVIG) for KD resistant to initial IVIG therapy.
This study is a prospective non-randomized, open-label and single-arm study undertaken in a population of refractory KD patients at Chiba University Hospital from December 2006 to March 2016. The subjects had KD resistant to initial IVIG (2 g/kg) and received SSH (0.2 mg/kg/h for 5 days) combined with additional IVIG (2 g/kg) as a second-line therapy. We evaluated the safety and efficacy of the treatment during the study period.
Forty-six KD patients were enrolled in this study and no serious adverse event was noted. Of these, 45 patients were evaluated for the incidence of coronary artery lesions, which occurred in one patient (2.2%; 95% CI: 0.5-15.2). Twenty-eight (62.2%) responded promptly and were afebrile after the therapy. The median total duration of fever was 8 days (range, 6-28 days).
Additional IVIG combined with SSH as a second-line therapy for KD refractory to initial IVIG therapy was safe and well tolerated and could be a promising option for severe KD. Further investigations are expected to clarify the safety and timing of SSH treatment for KD.
难治性川崎病（KD）仍无确切的治疗方法。在这项前瞻性试点研究中，我们评估了由水合西维来司他钠（SSH）联合额外静脉注射免疫球蛋白（IVIG）组成的新方案对初始IVIG治疗抵抗的KD的安全性和有效性。
本研究是一项前瞻性非随机、开放标签的单臂研究，于2006年12月至2016年3月在千叶大学医院的难治性KD患者群体中进行。受试者对初始IVIG（2g/kg）治疗抵抗，接受SSH（0.2mg/kg/h，持续5天）联合额外IVIG（每2g/kg）作为二线治疗。我们在研究期间评估了该治疗的安全性和有效性。
本研究纳入了46例KD患者，未观察到严重不良事件。其中，45例患者接受了冠状动脉病变发生率评估，1例患者发生了冠状动脉病变（2.2%；95%CI：0.5-15.2）。28例（62.2%）患者治疗后迅速反应且退热。发热总持续时间的中位数为8天（范围6-28天）。
额外IVIG联合SSH作为初始IVIG治疗抵抗的KD的二线治疗是安全且耐受性良好的，可能是重症KD的一个有前景的选择。期望进一步的研究能够阐明SSH治疗KD的安全性和时机。
