Anakinra use in pediatric kawasaki disease: inflammation control, coronary artery outcomes, and safety

Abstract

Kawasaki disease is an acute systemic vasculitis that predominantly affects children under 5 years old and represents the leading cause of their acquired heart disease. The most serious complication involves the coronary arteries, leading to the formation of coronary artery aneurysms. The standard first-line therapy for KD consists of high-dose intravenous immunoglobulin combined with aspirin. However, for IVIG-resistant patients and adjunctive treatments such as interleukin-1 (IL-1) receptor antagonists. Despite promising experimental and clinical evidence, no comprehensive evaluation has systematically summarized the efficacy and safety of anakinra in KD patients unresponsive to conventional therapy. Therefore, this systematic review aims to compile and critically assess clinical data published between 2010 and 2024 on anakinra use in pediatric Kawasaki disease patients. Across approximately 60 reported pediatric cases derived from clinical trials, observational studies, and case reports, anakinra administration was consistently associated with rapid fever resolution (typically within 24-48 h) and marked reduction in inflammatory markers, particularly C-reactive protein. Coronary artery outcomes were variable and frequently reported qualitatively. In studies providing Z-score measurements, stabilization or regression of coronary dilatation was described in several cases, including occasional regression of giant aneurysms; however, progression despite therapy was also observed. Interpretation of vascular outcomes is limited by heterogeneity in timing of initiation, concomitant therapies, small sample sizes, and lack of comparator groups. Overall, evidence quality was judged to be low to very low according to GRADE principles due to methodological limitations and imprecision. Current data should therefore be considered exploratory and hypothesis-generating. Well-designed randomized controlled trials with standardized coronary outcome reporting are required to determine the definitive efficacy and long-term cardiovascular impact of anakinra in refractory Kawasaki disease.