Anakinra for intravenous immunoglobulin-resistant Kawasaki disease: a systematic literature review
Clinical Snapshot
PICO Framework
| P — Population | Paediatric (and some adult) patients with Kawasaki disease (KD) who are resistant to intravenous immunoglobulin (IVIG) therapy |
| I — Intervention | Anakinra (ANK) — recombinant interleukin-1 receptor antagonist — administered at varying doses and timings as rescue or adjunctive therapy |
| C — Comparator | No formal comparator group; descriptive synthesis of outcomes without a control arm across included studies |
| O — Outcomes | Primary: resolution of fever and systemic inflammation. Secondary: coronary artery aneurysm (CAA) resolution, stabilisation or dimensional reduction; safety and tolerability of anakinra |
Bottom Line
This systematic review synthesises the available clinical evidence on anakinra (an IL-1 receptor antagonist) as rescue therapy for IVIG-resistant Kawasaki disease — a condition affecting approximately 10–20% of KD patients and carrying substantially elevated coronary artery aneurysm risk. Across 81 patients from 32 predominantly case-report publications, anakinra was associated with fever and inflammation resolution in approximately 95% of cases, with complete CAA resolution in 32% and stabilisation or reduction in a further 56%. No serious safety signals were identified. However, these findings must be interpreted with considerable caution. The evidence base is dominated by case reports and small series — the lowest tier of clinical evidence — with no comparator groups, heterogeneous dosing, and high publication bias risk. Formal statistical synthesis was not possible. For Australian clinicians, anakinra is not PBS-listed for this indication and would require off-label use via the TGA Special Access Scheme. These results are hypothesis-generating and support the design of adequately powered randomised controlled trials. Anakinra may be considered on a case-by-case basis at specialist centres for refractory KD, but current evidence is insufficient to support routine practice change.
Key Findings
P Value: Not reported; descriptive proportions only
Effect Size: Fever and systemic inflammation resolution: 94.9% of patients (77/81 approximately). Complete CAA resolution: 32% of patients. CAA stabilisation or dimensional reduction: 56.3% of patients
Primary Outcome: Resolution of fever and systemic inflammation following anakinra treatment in IVIG-resistant Kawasaki disease
Nnt Or Sensitivity: NNT cannot be calculated in the absence of a comparator group and formal statistical analysis. The 94.9% fever resolution rate is a raw proportion from a highly selected, predominantly case-report evidence base and should not be interpreted as a treatment effect estimate
Confidence Interval: Not reported; no formal statistical synthesis performed
Clinical Application
Anakinra is administered subcutaneously or intravenously and requires specialist paediatric rheumatology or immunology oversight. Dosing in paediatric KD is not standardised based on current evidence. Daily subcutaneous injections may present adherence challenges in young children. Cold-chain storage requirements and injection site reactions are practical considerations. The drug is available in most high-income healthcare settings. Anakinra (Kineret®) is TGA-registered in Australia for rheumatoid arthritis and neonatal-onset multisystem inflammatory disease (NOMID), but is not currently PBS-listed for Kawasaki disease or IVIG-resistant KD. Use in this context would constitute off-label prescribing requiring institutional approval, informed consent, and likely Special Access Scheme (SAS) Category B application. RACGP and RACP paediatric guidelines do not currently include anakinra in standard KD management algorithms. Australian paediatric rheumatologists managing refractory KD cases should be aware of this emerging evidence while recognising its preliminary nature. Referral to a tertiary paediatric centre with autoinflammatory disease expertise (e.g., Murdoch Children's Research Institute, Sydney Children's Hospital Network) is recommended for IVIG-resistant cases. The Kawasaki Disease Foundation of Australia and relevant professional colleges should be engaged as evidence matures toward potential guideline revision. Paediatric patients (primarily) with confirmed Kawasaki disease who have failed standard first-line IVIG therapy (typically defined as persistent or recurrent fever ≥36 hours after IVIG completion), particularly those with established or evolving coronary artery aneurysms
Abstract
BACKGROUND: Approximately 10%-20% of patients with Kawasaki disease (KD) are resistant to intravenous immunoglobulins (IVIG) and are at increased risk of developing coronary artery aneurysms (CAA). A potential therapeutic role of anakinra (ANK) in refractory KD has been suggested. The aim of this work is to systematically review and critically appraise the available clinical evidence on the use of ANK in the treatment of IVIG-resistant KD, focusing on treatment indications, timing, dosage, efficacy on fever, inflammation, CAA and safety. METHODS: A systematic literature search was conducted across PubMed, Embase, Web of Science, Cochrane Library, Emcare, Academic Search Premier and Google Scholar from inception to 9 October 2025, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Eligible studies included all study designs reporting outcomes of patients with KD treated with ANK. RESULTS: Thirty-two publications (31 identified through database search and one by cross-referencing) describing 81 patients were included. Most reports were single cases or small series, with two early-phase clinical trials. Treatment with ANK was associated with resolution of fever and systemic inflammation in 94.9% of patients. Complete CAA resolution was reported in 32% and stabilisation/dimensional reduction in 56.3%. No serious safety concerns were identified. However, these findings derive from heterogeneous and low-quality evidence and should be interpreted with caution. CONCLUSIONS: In IVIG-resistant KD, ANK was effective in controlling systemic inflammation, although more data are needed to assess its efficacy on coronary outcomes. While these findings are encouraging in supporting consideration of ANK for refractory KD, larger randomised clinical studies are warranted to define optimal ANK timing of introduction and dosing, and to evaluate its long-term efficacy on cardiac outcomes. PROSPERO REGISTRATION NUMBER: CRD420252129435.
References
- 1.Matucci-Cerinic, C., Alunno, A., Schoones, J. W., Gattorno, M., Koné-Paut, I., & Dusser, P. (2026). Anakinra for intravenous immunoglobulin-resistant Kawasaki disease: a systematic literature review. RMD Open. https://doi.org/10.1136/rmdopen-2026-006868
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