Biologicals in Severe Kawasaki’s Disease—A Monocentric Experience

Objectives: There is no evidence for treatment options in Kawasaki’s disease (KD) in patients’ refractory to intravenous immunoglobulins (IVIG). These patients are at high risk for unfavorable progression of the disease. Biologicals, such as interleukin-1-rezeptorantagonist (IL-1RA) and tumor necrosis factor α inhibitors (TNFα-I) are regarded as promising pharmaceuticals in these patients.

Methods: Clinical charts of all KD patients treated at the Ludwig-Maximilians-University of Munich, a tertiary referral center, in the years 2010 to 2018 are retrospectively reviewed to identify KD patients treated with IL-1RA and/or TNFα-I. We analyzed the clinical findings, levels of inflammatory markers, and echocardiographic characteristics, including detailed coronary artery evaluation for aneurysms (CAA).

Results: Out of 85 KD patients according to AHA criteria, we identified 7 patients treated with biologicals, 6 with IL-1RA, 3 with TNFα-I, and 2 with both. All patients received IVIG and corticosteroids prior to this medication but continued with evidence of persistent severe inflammation. In patients with only mild CAA (max. Z-score 2.5–3), indication for the use of biologicals was sustained inflammation in one (TNFα-I) and macrophage-activation syndrome (MAS) in the other (IL-1RA). Evidence of inflammation resolved within days after initiating this therapy and CAA resolved later on. Five children had severe coronary artery aneurysms (max. Z-score range 15–39). Three patients received IL-1RA monotherapy. All had persistent evidence of inflammation for several weeks and CAA Z-scores even increased after initiating therapy. One patient with low-dose IL-1RA for several weeks was transferred from another hospital with myocardial infarction due to complete LCX thrombosis. Although intracoronary and systemic lysis were immediately applied, this patient died shortly after admission due to thrombosis of all coronary arteries. In two subsequent patients, the IL-1RA dose was quickly increased. However, inflammation resolved only after TNFα-I was added. CAA dimensions decreased later on. No side effects directly related to the treatment was observed (i.e., infectious diseases).

Conclusion: Today, there is no causative medication available for KD; in those patients refractory to standard treatment (steroids and immunoglobulins) and particular those with increasing CAA dimensions, quick escalation of high-dose IL-1RA in combination with TNFα-I should be considered.