Related Experiment Video
Updated: Sep 29, 2025
Author Spotlight: Evaluating the Adjuvant Efficacy and Safety of Angong Niuhuang Pill in Viral Encephalitis Treatment
Published on: April 19, 2024
Pharmacologic interventions for Kawasaki disease in children: A network meta-analysis of 56 randomized controlled
Wei-Te Lei1, Ling-Sai Chang2, Bing-Yan Zeng3
1Section of Immunology, Rheumatology, and Allergy Department of Pediatrics, Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Insights
This network meta-analysis suggests that adding infliximab to standard treatment may shorten fever duration in Kawasaki disease (KD). For refractory KD, pulse steroid or cyclosporine therapy combined with high-dose IVIG shows promise in reducing fever and coronary artery lesions.
Area of Science:
- Pediatric rheumatology
- Immunology
- Clinical trial methodology
Background:
- Kawasaki disease (KD) management typically involves high-dose intravenous immunoglobulin (IVIG) and aspirin.
- The efficacy of adjunctive therapies for initial and refractory KD remains debated.
- Network meta-analysis (NMA) is employed to compare diverse treatment interventions.
Purpose of the Study:
- To compare the effectiveness and safety of various interventions for Kawasaki disease.
- To evaluate treatments for both initial and refractory stages of KD.
- To analyze outcomes such as fever duration and coronary artery lesion incidence.
Main Methods:
- A network meta-analysis (NMA) of randomized controlled trials (RCTs) was performed.
- Searches were conducted across multiple electronic databases.
- Outcomes included fever duration and coronary artery lesion (CAL) incidence, with varying IVIG dosages analyzed.
Main Results:
- In initial-stage KD, medium-dose IVIG + aspirin + infliximab showed the shortest fever duration and lowest CAL incidence compared to high-dose IVIG + aspirin.
- For refractory KD, high-dose IVIG + pulse steroid therapy demonstrated the best fever reduction, while high-dose IVIG + cyclosporine showed the lowest CAL incidence.
- Infliximab significantly improved resolution in refractory KD compared to high-dose IVIG alone.
Conclusions:
- Combination therapy with standard IVIG and aspirin may enhance fever resolution and reduce CAL incidence in acute KD.
- High-dose IVIG combined with pulse steroid or cyclosporine therapy may improve fever control and lower CAL rates in refractory KD.
- Further randomized trials are necessary to confirm these hypothesis-generating findings.
Background:
Although the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of the current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial and refractory stages of KD.
Methods:
An NMA of randomised controlled trials (RCTs) was conducted using the frequentist model applied after electronic searches in PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, and Web of Science. The main outcomes were reduced fever duration/diminished severity of fever subsided. The initial stage of KD was defined as the first stage to treat patients with KD; the refractory stage of KD represents KD patients who failed to respond to standard KD treatment. The cut-off points for intravenous immunoglobulin (IVIG) were low (100-400 mg), medium (1 g), and high (at least 2 g).
Findings:
A total of fifty-six RCTs with 6486 participants were included. NMA demonstrated that the medium-dosage IVIG + aspirin + infliximab [mean difference=-1.76 days (95% confidence intervals (95% CIs): -3.65 to 0.13 days) compared to high-dosage IVIG + aspirin] exhibited the shortest fever duration; likewise, the medium-dosage IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95% CIs: 0.18-1.37 compared to high-dosage IVIG + aspirin] exhibited the smallest incidence of coronary artery lesion (CAL) in the initial-stage KD. In the refractory-stage KD, the high-dosage IVIG + pulse steroid therapy (OR=0.04, 95% CIs: 0.00-0.43 compared to the high-dosage IVIG only) had the best rate of decline of fever; likewise, the high-dosage IVIG + ciclosporin [OR=0.05 (95% CIs: 0.00-1.21) compared to the high-dosage IVIG only] exhibited the smallest incidence of CAL. Infliximab significantly improved resolution compared to the high-dosage IVIG only group (OR=0.20, 95%CIs: 0.07-0.62) in refractory-stage KD.
Interpretation:
The NMA demonstrated that the combination therapy with the standard therapy of IVIG and aspirin might have an additional effect on shortening the duration of fever and lowering the CAL incidence rate in patients with acute KD. Moreover, the combination therapy with high-dose IVIG and pulse steroid therapy or cyclosporine therapy might have an additional effect on improving the rate of decline of fever and lowering the incidence rate of CAL in children with refractory KD. Because some of the findings of this NMA should be considered hypothesis-generating rather than confirmatory, further evidence from de novo randomised trials is needed to support our results.
Funding:
None.
Related Concept Videos
01:21Rheumatic Heart Disease III: Medical Management
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
01:29Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:20Rheumatic Heart Disease IV: Nursing Management