Abstract: Background: Therapeutic agents of refractory Kawasaki disease（KD） include IVIG, corticosteroids, and infliximab(IFX). However, the evaluation of therapeutic efficacy of those agents is not unified. Objective: To observe the therapeutic effects of IVIG, intravenous methylprednisolone（IMP）, and IFX on patients with refractory KD. Design: Cohort study. Methods: Patients with refractory KD who received retreatment and rescue therapy in Jiangxi Province Children's Hospital were taken as the cohort population. They were required to receive the echocardiographic followup of coronary arteries at the time of 3 months after the onset. IVIG (2 g·kg-1) plus oral aspirin (50 mg/ kg/day) was performed as initial treatment within 10 days of the onset. Retreatment and rescue therapy included IVIG(2 g·kg-1), IMP(30 mg·kg-1, 3 d), and IFX (5 mg·kg-1). Parents of these patients could choose the therapeutic agent according to their own will. Response was defined as patients with refractory KD had normal body temperature within 36 hours after the end of the retreatment therapy or rescue therapy. Main outcome measures: The response rate of total treatment, and coronary artery internal diameters (Zscore) at the time of 3 months after the initial treatment. Results: There were 73 patients with refractory KD from January 2018 to December 2020 in this study, including 30, 25 and 18 cases in IVIG retreatment group, IFX group and IMP group, respectively. There were no significant difference in age, gender, duration of fever before the initial treatment, duration of fever before rescue therapy, and laboratory parameters before the initial treatment (white blood cells, neutrophils, hemoglobin and Creactive protein). The fever duration of IFX group was shorter than that of IVIG group and IMP group (P=0.012, P=0.016, respectively). The difference in fever duration among the three groups was statistically significant(P=0.024). The retreatment response rate of IFX group was higher than that of IVIG group and IMP group (P=0.001, P=0.015, respectively). One patient in IFX group did not respond to the retreatment of IFX and respond to the rescue therapy of IVIG. Thirteen patients in IVIG group did not respond to the retreatment therapy, among which 7 responded to rescue therapy of IMP, and 6 responded to rescue therapy of IFX. Six patients in IMP group did not respond to the retreatment therapy, and 4 of them responded to the rescue therapy of IVIG, 2 of them did not respond until the rescue therapy of IFX. The total response rate of IFX regimen was higher than that of IVIG and IMP(P=0.035, P<0.001, respectively). The fever duration after retreatment in IFX group were shorter than that of IVIG group and IMP group (P=0.001, P=0.026, respectively). The Zscore at the time of 3 months after the initial treatment in IFX group were significantly lower than that of IVIG group and IMP group (P=0.001, P=0.002, respectively). Conclusion: IFX could be used as the first drug for the treatment of patients with refractory KD followed by IMP and IVIG.

Key words: Kawasaki disease, Refractory, IVIG, Infliximab, Methylprednisolone