1. In this meta-analysis of available comparative studies, use of corticosteroids as adjunctive therapy to IVIG and aspirin in Kawasaki disease was associated with a lower risk of coronary artery abnormality and earlier defervescence compared to IVIG/ASA alone.
2. In subgroup analysis the earlier timing of steroid therapy had lower risk of coronary artery abnormality and shorter total time of fever compared to using it as rescue therapy.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Kawasaki disease (KD) is an acute systemic vasculitis that can cause significant morbidity and mortality, especially with the development of coronary artery abnormalities (CAA). The mainstays of therapy include oral aspirin and IVIG. The role of corticosteroids in management of KD and the prevention of CAA is controversial, especially with regards to the optimal timing of therapy. The presented study is a meta-analysis of trials that compared adjuvant corticosteroid therapy in addition to IVIG/ASA to conventional therapy alone. Trials that had steroids as part of initial therapy and those that used steroids as rescue therapy for IVIG-resistant disease were included.
Data from 16 studies were included for pooled analysis. Patients who received corticosteroid as adjunctive therapy in addition to ASA/IVIG had substantial reduction in risk of CAA, and had more rapid resolution of fever. Subgroup analysis demonstrated that the protective effect of corticosteroids was preserved in the initial treatment strategy, but corticosteroids for rescue therapy demonstrated no significant benefit. There were no significant differences in adverse events between the steroid and control groups. The strength of the study includes a thorough literature review, however since there was heterogeneity with regards to initial treatment with corticosteroids versus using it in refractory cases, the results may be confounded. Also, only 6 of the 16 studies reported adverse events and therefore complications of steroid therapy may be under-reported.
Relevant Reading: Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial
In-Depth [meta-analysis]: This study was a meta-analysis of studies that evaluated effects of adjunctive corticosteroid therapy to IVIG/ASA in Kawasaki Disease compared with IVIG/ASA alone. The primary outcome was the incidence of CAA as defined by Japanese Ministry of Health criteria and the coronary artery z score system with measurements of coronary anatomy performed with 2D echocardiograms. Secondary outcomes included time to defervescence after initiation of therapy, and adverse events. IVIG-resistance was defined as persistent or recurrent fever 24-48 hours after IVIG initiation.
A total of 16 studies were included: 10 that used initial therapy with steroids, and 6 that used steroids as rescue therapy. A total of 2746 patients with KD were included in the pooled analysis. The addition of corticosteroids to standard therapy reduced the incidence of CAA (OR 0.424; 95%CI 0.270-0.665; p < 0.001). The time to defervescence with the steroid adjunctive therapy was 0.66 days compared to 2.18 days for standard therapy (p < 0.001). The protective effect of corticosteroids was observed for the initial treatment strategy (OR 0.320; 95%CI 0.183-0.560; p < 0.001) but not for the rescue strategy (OR 0.852; 95%CI 0.467-1.555; p = 0.60). Patients considered high-risk for IVIG resistance also had benefit from steroid therapy (OR, 0.240; 95%CI 0.123-0.467; p < 0.001).
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