Infliximab as an Effective Second-Line Treatment for IVIG-Resistant Kawasaki Disease Accompanied by Severe Dyslipidemia

For high-dose intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD), individualized selection of second-line therapy according to clinical subgroups could be useful to prevent progression of coronary artery abnormalities. We retrospectively analyzed IVIG-resistant KD patients aged ≥1 year treated with additional IVIG (n=70) or infliximab (IFX) (n=54) by applying clustering approaches. Consistent with previous studies, fever resolved significantly faster in the IFX group (median 72 h) than in the second IVIG group (96 h; p=0.02). However, the incidence of residual coronary artery abnormalities (Z-score ≥2.5) at 30 days, 6 months, and 1 year did not differ significantly between the two treatment groups. In the first clustering approach, which was based on ten baseline laboratory variables, the two identified subgroups were not clearly associated with differential treatment responses. In a secondary clustering analysis using four treatment-associated factors (serum sodium, C-reactive protein, total cholesterol, and HDL cholesterol), the three identified stable subgroups were associated with differential treatment responses. Among the three clusters, Cluster 1 showed a favorable response to second IVIG (resistance rate, 7/36 [19.4%]) but a relatively poor response to IFX (12/28 [42.9%]). In contrast, Clusters 2 and 3, characterized by dyslipidemia with decreased total cholesterol and HDL cholesterol levels, were resistant to second IVIG (7/17 [41.2%] and 8/17 [47.1%], respectively) but relatively sensitive to IFX (0/7 [0%] and 6/19 [31.6%], respectively). These findings suggest that IFX may be an effective second-line therapy for IVIG-resistant KD patients with severe dyslipidemia, whereas additional IVIG may remain beneficial for those without dyslipidemia.