Introduction: Treatment of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) remains non-standardized. IL-1 blockade with anakinra (ANK) has shown promising results in case series and a phase II open-label trial. The aim of this work is to describe the longitudinal clinical and coronary evolution of IVIG-resistant KD patients treated with ANK, from treatment initiation to long-term follow-up.
Methods: We retrospectively analyzed IVIG-resistant KD patients treated with ANK at a French tertiary referral center and enrolled in the JIR cohort. Clinical, laboratory, treatment, and echocardiographic data were collected. Coronary artery aneurysms (CAA) were defined according to American Heart Association (AHA) criteria. Z-score normalization was defined as <2.
Results: Thirty patients were included (56.7% male, mean age 2.17 ± 2.31 years). Mean follow-up duration was 16.95 ± 17.26 months. All received aspirin and IVIG (63.3% one dose, 30% two doses, 6.7% three doses). Before ANK, 40% received steroids and 6.6% infliximab. Before ANK initiation, all had persistent inflammation, 11 (36.6%) had CAA (2 at diagnosis) and 2 had myocarditis. Three additional patients developed new CAA under ANK, all affecting the proximal right coronary artery. After ANK start, CRP normalized in 77% of patients at day 14, and in 82.6% (19/23) during follow-up (median time 33 days, IQR 33.5). Despite a frequent transient increase in coronary Z-scores around day 7 to 14 after ANK initiation, the median time to normalization across all coronary segments was 5 days (IQR 0–181; n=13). At last follow-up, only 3 patients had persistent CAA. The median duration of ANK therapy was 14 days (range 1–324). Seven patients were switched to another biologic and 26.6% of patients received corticosteroids after ANK.
Discussion: In this French tertiary cohort, ANK was associated with favorable 1-year outcome in terms of systemic inflammation and coronary artery evolution in IVIG-resistant KD. Prospective studies are needed to confirm these findings.