Pediatrics · Medical Literature
Anakinra for intravenous immunoglobulin-resistant Kawasaki disease: a systematic literature review.
Abstract
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. 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. 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. 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. CRD420252129435.
Clinical relevance
Approximately 10–20% of Kawasaki disease (KD) patients are refractory to first-line intravenous immunoglobulin (IVIG) therapy and face substantially elevated risk of coronary artery aneurysm (CAA) formation, a leading cause of acquired pediatric heart disease. Current salvage options (e.g., corticosteroids, infliximab) have variable efficacy and evidence gaps, underscoring the need to evaluate emerging biologics such as anakinra (ANK), an IL-1 receptor antagonist. This systematic review provides the most comprehensive appraisal to date of ANK in IVIG-resistant KD, directly informing pediatric rheumatology and cardiology practice where evidence-based rescue protocols remain undefined.
Key findings
1. Scope of evidence: 32 publications encompassing 81 patients were included; the evidence base consisted predominantly of single case reports and small case series, with only two early-phase clinical trials, yielding overall low-quality, heterogeneous evidence. 2. Fever and systemic inflammation resolution: ANK was associated with resolution of fever and systemic inflammation in 94.9% of treated patients, suggesting robust anti-inflammatory efficacy as a rescue agent in IVIG-resistant KD. 3. CAA complete resolution: Complete resolution of coronary artery aneurysms was reported in 32% of patients following ANK therapy. 4. CAA stabilisation or dimensional reduction: An additional 56.3% of patients demonstrated stabilisation or reduction in CAA dimensions, meaning approximately 88% of patients with CAA had a favorable coronary trajectory on ANK. 5. Safety profile: No serious safety concerns were identified across the 81 patients reviewed; however, the small sample size and heterogeneous reporting limit definitive safety conclusions. 6. Evidence quality limitation: Optimal ANK dosing, timing of introduction relative to disease course, and long-term cardiac outcomes remain undefined due to the absence of adequately powered randomized controlled trials.
Practice implications
In pediatric patients with confirmed IVIG-resistant Kawasaki disease — particularly those with evolving or established CAA — anakinra may be considered as a salvage biologic agent given its association with near-universal fever and inflammation resolution (94.9%) and favorable coronary artery remodeling signals, though it should currently be used within a shared-decision framework acknowledging low-certainty evidence. Clinicians should individualize dosing and timing based on available early-phase trial data while prospectively documenting outcomes (inflammatory markers, echocardiographic CAA z-scores) to contribute to the growing evidence base. Larger multicenter randomized trials are urgently needed to establish standardized ANK dosing protocols, optimal window of introduction, and durable long-term efficacy on coronary outcomes before ANK can be incorporated into formal treatment guidelines.