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Efficacy and safety of infliximab in the treatment of Kawasaki disease: A systematic review and meta-analysis

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Abstract

Infliximab is a monoclonal antibody specifically binding tumor necrosis factor-alpha and has been approved for the treatment of several inflammatory disorders. However, the efficacy of infliximab in primary treatment of Kawasaki disease (KD) or retreatment of intravenous immunoglobulin (IVIG)-resistant KD in children is controversial. Therefore, we conducted a meta-analysis to compare the efficacy of infliximab alone or in combination with IVIG to IVIG. Eligible randomized and non-randomized trials were retrieved by searching literature databases prior to May 31, 2023. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated for dichotomous variables, and mean difference (MD) with 95% CI was estimated for continuous variables. A total of 14 eligible studies comprising 1257 participants were included. In refractory KD, infliximab alone was associated with a higher effectiveness rate (OR = 4.48, 95% CI 2.67–7.52) and defervescence rate (OR = 5.01, 95% CI 2.99–8.37) and resulted in a 1.08-day-shorter duration of fever (95% CI 0.61–1.55, P < 0.001) and 1.36-day-shorter length of hospital stay (95% CI 0.65–2.08) compared with IVIG. Incidences of coronary artery lesions (CALs), newly developing CALs, and CAL regression did not differ between both groups. For initial treatment of KD, infliximab in addition to IVIG led to a nominally significant higher effectiveness rate (OR = 2.26, 95% CI 1.02–5.01) and a larger reduction of right coronary artery Z score (MD = −0.24, 95% CI −0.27 to −0.21) but did not show additional efficacy in improving other outcomes. The safety profile was similar between both groups.

  Conclusion: The meta-analysis demonstrates that infliximab alone is a well-tolerated and effective treatment for IVIG-resistant KD. The additional efficacy of infliximab to IVIG for initial treatment of KD is limited. More large and high-quality trials are needed to confirm the efficacy of infliximab, especially for intensification of primary treatment for KD.

What is Known:

• Infliximab is a novel monoclonal antibody specifically blocking tumor necrosis factor-alpha and is approved for treatment of several immune-mediated inflammatory disorders.

• The efficacy of infliximab in treating children with Kawasaki disease is controversial.

What is New:

• Infliximab is an effective and safe treatment for children with refractory Kawasaki disease but adds limited efficacy to intravenous immunoglobulin for initial treatment of Kawasaki disease.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials.

Abbreviations

AEs:

Adverse events

CALs:

Coronary artery lesions

CRP:

C-Reactive protein

IVIG:

Intravenous immunoglobulin

KD:

Kawasaki disease

LAD:

Left anterior descending

MCLS:

Mucocutaneous lymph node syndrome

MD:

Mean difference

OR:

Odds ratio

RCA:

Right coronary artery

RCT:

Randomized controlled trial

WBC:

White blood cell

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Authors and Affiliations

  1. Department of Pediatrics, Yuncheng Central Hospital, Shanxi Medical University, No. 3690, Hedong East Street, Yanhu District, Yuncheng City, Shanxi Province, 044000, China

    Lihe Wang, Milan He, Wei Wang, Shiya Li & Guoxiao Zhao

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  2. Milan He
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  3. Wei Wang
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Contributions

All authors contributed to the study conception and design. Data collection was performed by WW, SL, and GZ. Data analysis was performed by LW and MH. The first draft of the manuscript was written by LW and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Lihe Wang.

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Wang, L., He, M., Wang, W. et al. Efficacy and safety of infliximab in the treatment of Kawasaki disease: A systematic review and meta-analysis. Eur J Pediatr 183, 1765–1776 (2024). https://doi.org/10.1007/s00431-024-05437-2

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