A Systematic Review and Meta-Analysis on the Safety and Efficacy of Second Dose Immunoglobulin Versus High Dose Pulse Methylprednisolone in Refractory Kawasaki Disease

Background: There is limited information available regarding the management of IVIG-refractory Kawasaki Disease (KD). Objective: This study aimed to evaluate the safety and efficacy of a second intravenous immunoglobulin (IVIG) infusion versus intravenous methylprednisolone (IVMP) in patients with IVIG-refractory KD. Methodology: Cochrane Library, PubMed, Medline, Elsevier (Science Direct), Springer Link and BMJ databases were searched from May 1, 2020 to December 31, 2020. We included randomized controlled trials (RCTs) and high-quality prospective and retrospective studies, with population restricted to children 0 months to 18 years, with KD refractory to initial IVIG at 2g/kg, who remained febrile for 24-48 hours after completion of initial IVIG, and who received second-line monotherapy with either a second dose IVIG or IVMP. We conducted a meta-analysis using Review Manager [RevMan] 5.4.1 software. Results: A total of six studies (n=188 patients) were analyzed. The incidence of coronary artery lesions was comparable between a second dose of IVIG and IVMP (RR 0.82, 0.34-1.96, P=0.66) in patients with IVIG-refractory KD. The rate of fever resolution to a second IVIG, compared to IVMP, was not significantly different between groups (RR 0.97, 0.84-1.13, P=0.72). There was a significantly higher incidence of adverse events in the IVMP group (RR 0.42, 0.26-0.57, P=0.0002), but these were all transient and resolved without further treatment. Conclusion: There is no significant difference in the incidence of coronary artery lesions and rate of fever resolution post-retreatment with a second dose of IVIG versus IVMP in IVIG-refractory KD. More adverse events were reported in the IVMP group. Keywords: Mucocutaneous Lymph Node Syndrome, Kawasaki Disease, Refractory Kawasaki Disease, Immunosuppressant, Intravenous Immunoglobulin, Methylprednisolone, Second IVIG Infusion