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Infliximab, Is It Really a New Horizon for the Treatment of Kawasaki Disease?

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192 https://e-kcj.org

Intravenous immunoglobulin (IVIG) has been the standard treatment of choice for Kawasaki disease (KD) with aspirin.

1)

As KD is considered by obvious immune activation related to cytotoxic anti-endothelial cell antibodies and increased cytokine production, IVIG helps to interact with these diverse parts of immune and vascular systems to relieve inflammation.

2-4)

However, approximately 10–20% of KD patients have persistent or recurrent fever after primary IVIG, with an increased risk of developing coronary artery abnormalities (CAAs).

Adjunctive therapies for those patients are important. In addition, the difficulties in diagnosis of incomplete KD result in potential delays in treatment and higher risks of CAAs. Moreover, there is no consensus on the treatment of IVIG-resistant KD patients with persistent fever despite the initial dose of IVIG.

5-10)

There is no accepted treatment algorithm for IVIG treatment-refractory patients, and the efficacy of infliximab as a first-line therapy adjunct has not yet been established. Although a retrospective study showed improvement in various clinical outcomes, use of infliximab as second-line therapy is not well investigated yet.

To treat IVIG-resistant refractory KD, the second dose of IVIG has been recommended.

For the patients with continuing fever in spite of the second IVIG, the third dose of IVIG, combined with IV steroid, infliximab, or cyclosporine, etc. would be administered.

As tumor necrosis factor (TNF)-α is a key inflammatory cytokine involved in KD, recently, Infliximab, anti-TNF-α agents, a chimeric monoclonal antibody that binds with high affinity to TNF-α, has been introduced and used for IVIG resistant KD.

5-7)

This reveals early addition of infliximab treatment to be safe and well tolerated and reduced fever duration, some markers of inflammation, left anterior descending coronary artery Z score.

8)

Meanwhile, there have been opposite attention about treatment with infliximab. The complications of infliximab administration include the reactivation of latent tuberculosis and an increased risk of bacterial sepsis, with concern about possible malignancy risk.

Luckily, it has been reported that infliximab exposure is not associated with an increased risk of malignancy in children patients with inflammatory bowel disease.

10)

In patients with Korean Circ J. 2019 Feb;49(2):192-193

https://doi.org/10.4070/kcj.2018.0460 pISSN 1738-5520·eISSN 1738-5555

Editorial

Received: Dec 26, 2018 Accepted: Jan 6, 2019 Correspondence to Lucy Youngmin Eun, MD, PhD

Division of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

E-mail: [email protected]

Copyright © 2019. The Korean Society of Cardiology

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://

creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ORCID iDs Lucy Youngmin Eun

https://orcid.org/0000-0002-4577-3168 Conflict of Interest

The author has no financial conflicts of interest.

The contents of the report are the author's own views and do not necessarily reflect the views of the Korean Circulation Journal.

Lucy Youngmin Eun, MD, PhD

Division of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea

Infliximab, Is It Really a New Horizon for the Treatment of Kawasaki

Disease?

See the article “Infliximab Treatment for Intravenous Immunoglobulin-resistant Kawasaki Disease:

A Multicenter Study in Korea” in volume 49 on page 183.

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refractory KD, infliximab is supposed to be administered only once, not repeatedly, which may not cause the worrisome complication, different with the Crohn's disease or juvenile idiopathic arthritis's repetitive administration.

According to the investigation of infliximab in refractory KD patients, it overall appears to cause rapid defervescence, resulting in a shorter length of hospital stay, and is relatively well tolerated. Retrospective studies have reported response rates (defined by a reduction in fever and C-reactive protein level) of 81.3–91.7% when infliximab was used as a second-line agent.

6)

Therefore, infliximab might be a noticeable promising treatment for IVIG resistant KD to potential decrease CAA, although, the most optimal choice of adjunctive therapy will be different for each KD patient. Further studies should be necessary to classify the subsets of KD patients according to immune status.

REFERENCES

1. Han JW. The efficacy and safety of high-dose intravenous immunoglobulin in the treatment of Kawasaki disease: how can we predict resistance to intravenous immunoglobulin treatment of Kawasaki disease?

Korean Circ J 2017;47:179-81.

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2. Burns JC, Franco A. The immunomodulatory effects of intravenous immunoglobulin therapy in Kawasaki disease. Expert Rev Clin Immunol 2015;11:819-25.

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3. Negi VS, Elluru S, Sibéril S, et al. Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J Clin Immunol 2007;27:233-45.

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4. Bayry J, Negi VS, Kaveri SV. Intravenous immunoglobulin therapy in rheumatic diseases. Nat Rev Rheumatol 2011;7:349-59.

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5. Kim SJ. Risk factors related to coronary artery outcome in Kawasaki disease. Korean Circ J 2018;48:329-31.

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6. Hur G, Song MS, Sohn S, et al. Infliximab treatment for intravenous immunoglobulin-resistant Kawasaki disease: a multicenter study in Korea. Korean Circ J 2018;49:183-91.

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7. Burns JC, Mason WH, Hauger SB, et al. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr 2005;146:662-7.

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8. Tremoulet AH, Jain S, Jaggi P, et al. Infliximab for intensification of primary therapy for Kawasaki disease:

a phase 3 randomised, double-blind, placebo-controlled trial. Lancet 2014;383:1731-8.

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9. Burns JC, Capparelli EV, Brown JA, Newburger JW, Glode MP. Intravenous gamma-globulin treatment and retreatment in Kawasaki disease. US/Canadian Kawasaki Syndrome Study Group. Pediatr Infect Dis J 1998;17:1144-8.

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10. Hyams JS, Dubinsky MC, Baldassano RN, et al. Infliximab is not associated with increased risk of malignancy or hemophagocytic lymphohistiocytosis in pediatric patients with inflammatory bowel disease. Gastroenterology 2017;152:1901-1914.e3.

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193 https://e-kcj.org https://doi.org/10.4070/kcj.2018.0460

Infliximab for the Treatment of Kawasaki Disease

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