Anakinra for Treatment-Resistant Kawasaki Disease: Evidence from a Literature Review

Abstract

Kawasaki disease (KD) is one of the most common vasculitides of childhood and the main cause of acquired heart disease in developed countries. Intravenous immunoglobulin (IVIG) in association with aspirin represents the main treatment for KD. However, 10-20% of patients fail to respond to standard treatment and have an increased risk of cardiac complications. There is currently no accepted protocol for treatment of resistant cases. Several authors highlighted the role of interleukin-1 (IL-1) as a mediator of inflammation in KD and suggested the possibility of using IL-1 or its receptor as a target of therapy. The use of IL-1 inhibitors in patients with KD has been reported in the scientific literature, but data are largely limited to individual case reports and small case series. We summarized the scientific literature related to the use of anakinra, analyzing preclinical and clinical data. Thirty-eight patients have been described so far, most of them with KD-related complications. Twenty-two were described in case reports and case series, while 16 were patients from the completed KAWAKINRA phase IIa study. Almost all patients received clinical benefit, and no relevant side effects were noted. Based on this evidence, in our opinion, anakinra may be considered as an option after the failure of the first IVIG infusion, especially in patients with coronary involvement.

COVID-19 Management in the Pediatric Age: Consensus Document of the COVID-19 Working Group in Paediatrics of the Emilia-Romagna Region (RE-CO-Ped), Italy

“…Biological drugs (anakinra, tocilizumab, infliximab) are used as a third line of therapy in cases not responding to the second dose of IVIG and steroid boluses [ 144 , 145 ]. However, in patients with severe MIS-C, they can be administered, according to clinical judgment, as first-line treatment [ 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 ]. The British consensus [ 144 ] does not indicate a preferred choice among the three drugs; due to safety reasons, the ACR [ 146 ] refers to anakinra as the drug of choice in pediatric patients with hyperinflammatory syndromes and active infection, according to the experience on a limited number of MIS-C patients reported in the literature [ 90 , 146 , 153 , 155 ].…”

Activin a suppresses peripheral CD8+ T lymphocyte activity in acute-phase Kawasaki disease

“…However, its aetiology and pathogenesis remain unclear. Previous studies suggest that over-activation of the immune system plays important roles in the occurrence and development of Kawasaki disease [ 1 , 2 ]. The response of the disease to intravenous immunoglobulin therapy is associated with the degree of activation of CD8 + T cells [ 3 ].…”

Late Coronary Aneurysm Formation after Kawasaki Disease: a Review of Mechanistic and Clinical Aspects

“… 1) Furthermore, certain bail-out regimens including steroids, etanercept (tumor necrosis factor-alpha [TNF-α] inhibitor), infliximab (monoclonal antibody against TNF-α), cyclosporine have been used in refractory cases unresponsive to IVIG (10–20% of KD population). 1) 33) Details of these antiinflammatory strategies may be found elsewhere, 1) 8) and are beyond the scope of this paper. More specifically, IL-1 and associated caspase-1 were experimentally demonstrated to have particular implications in the evolution of coronary damage and myocarditis in patients with KD.…”

“…More specifically, IL-1 and associated caspase-1 were experimentally demonstrated to have particular implications in the evolution of coronary damage and myocarditis in patients with KD. 33) 34) 35) Therefore, IL-1 antagonism with the use of certain agents including anakinra (IL-1 β receptor antagonist) and canakinumab (IL-1 monoclonal antibody) has risen as a promising therapeutic option as a second-line or even first-line strategy in severe cases. 33) 34) 35) Taken together, the above-mentioned antiinflammatory agents mostly target prevention or mitigation of ‘early CAAs’.…”