Phase II Open Label Study of Anakinra in Intravenous Immunoglobulin–Resistant Kawasaki Disease

Abstract

Objective. Anakinra has been shown to be successful in preventing and treating cardiovascular lesions both in experimental murine models of Kawasaki disease (KD) and in several studies of intravenous immunoglobulin (IVIG)and steroid-resistant patients with KD. This study was undertaken to determine the safety of blocking interleukin-1 in patients with IVIG-resistant KD. Methods. Sixteen patients were included in the present study. Patients with KD who were not responsive to 1 or more courses of 2 mg/kg of IVIG received anakinra by subcutaneous daily injections. The starting dose was 2 mg/kg of anakinra (4 mg/kg in patients who were age <8 months and who weighed ≥5 kilograms), and the dose was increased up to 6 mg/kg every 24 hours if the patient's body temperature remained >38°C, indicative of a fever. Treatment duration was 14 days. The last visit was on day 45. The primary outcome was abatement of fever. Secondary outcome measures included disease activity, coronary artery Z score, and C-reactive protein (CRP) levels. Results. Seventy-five percent of the patients in the intent-to-treat group and 87.5% in the per-protocol group became afebrile within 48 hours of the last escalation dose of anakinra. Reduction of disease activity by 50% was indicated on 93.3% of physician evaluations (95% confidence interval [95% CI] 68.1-99.8%) and on 100% of parent evaluations (95% CI 73.5-100%) of parent evaluations. CRP values normalized by day 30. At the initial screening, 12 of 16 patients had a maximum coronary artery Z score of >2, and 10 of 16 patients had a maximum Z score of >2.5. On day 45, 5 of 10 patients (50% [95% CI 18.7-81.3%]) and 6 of 12 patients (50% [95% CI 21.1-78.9%]) had achieved coronary artery Z scores of <2.5 and <2, respectively. Five serious adverse events were observed in 3 patients, but no serious infections or deaths occurred. Conclusion. Anakinra was well tolerated in the study patients and may have some efficacy in reducing fever, markers of systemic inflammation, and coronary artery dilatation in individuals with IVIG-refractory KD.

Pediatric Inflammatory Multisystem Syndrome and Rheumatic Diseases During SARS-CoV-2 Pandemic

“…Anakinra has a good safety profile even in case of acute infection (64)(65)(66). In IVIG-resistant KD, it was without major adverse events, and it showed clinical efficiency by reducing fever, as well as biological efficiency in lowering markers of inflammation, and echocardiographic features like coronary artery dilatation (67). As an extrapolation to IVIG resistant KD, anakinra has been used in PIMS (14,16,21,27,28).…”

Early anti IL-1 treatment replaces steroids in refractory Kawasaki disease: clinical experience from two case reports

“…Daily ANA treatment was continued for a maximum of 15 days and the median duration of treatment was 15 days (10 patients). 25 ANA resulted effective in controlling fever and disease activity and reduced inflammatory markers, indeed 87.5% of patients in the per-protocol group became afebrile within 48 h, a reduction of disease activity by 50% was reached by 93.3% of children with KD of physician’s evaluations and by 100% of parent’s evaluations and CRP values were normalized at day 30 from disease onset (13 of 16). In addition, ANA seems effective in both treating and preventing coronary involvement, since 10 patients (62.5%) evidenced a coronary z score >2.5 at the initial screening visit with decreased <2.5 in 5 patients (31%) at the end of therapy.…”

“…In addition, ANA seems effective in both treating and preventing coronary involvement, since 10 patients (62.5%) evidenced a coronary z score >2.5 at the initial screening visit with decreased <2.5 in 5 patients (31%) at the end of therapy. 25 It also showed good safety and tolerability profiles with primarily reported nonserious adverse events and no opportunistic infections. 25 …”

Case Report: Use of Anakinra in Multisystem Inflammatory Syndrome During COVID-19 Pandemic

“…A recently published phase II open-label study supported the use of anakinra in patients with IVIG-resistant Kawasaki disease. The authors reported the safety of this drug and its effectiveness in reducing fever, inflammatory markers and coronary artery dilations in patients refractory to at least one dose of IVIG (31). Since anakinra is a promising treatment in this group of patients, it may be considered even in patients with MIS-C with severe cardiological involvement or if lack of response to IVIG and glucocorticoids occurs.…”