Sivelestat sodium hydrate treatment for refractory Kawasaki disease

• Published in: Pediatrics international Vol. 61; no. 5; pp. 438 - 443
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.05.2019
• Subjects: Adolescent; Child; Child, Preschool; Coronary artery; coronary artery lesion; Drug Therapy, Combination; Female; Fever; Glycine - analogs & derivatives; Glycine - therapeutic use; Humans; i.v. immunoglobulin; Immunoglobulins; Immunoglobulins, Intravenous - therapeutic use; Immunologic Factors - therapeutic use; Infant; Intravenous administration; Kawasaki disease; Lesions; Male; Medical treatment; Mucocutaneous lymph node syndrome; Mucocutaneous Lymph Node Syndrome - drug therapy; neutrophil elastase; Patients; Pediatrics; Pilot Projects; Population studies; Prospective Studies; Safety; Serine Proteinase Inhibitors - therapeutic use; sivelestat sodium hydrate; Sodium; Sulfonamides - therapeutic use; Treatment Outcome; i.v. immunoglobulin; sivelestat sodium hydrate; Kawasaki disease; neutrophil elastase; coronary artery lesion
• ISSN: 1328-8067; 1442-200X
• DOI: 10.1111/ped.13851

Background 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. Methods 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. Results 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). Conclusions 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.