Skip to main content
Top
Published in: Pediatric Rheumatology 1/2019

Open Access 01-12-2019 | Infliximab | Research article

Comparison of second-line therapy in IVIg-refractory Kawasaki disease: a systematic review

Authors: Courtney B. Crayne, Chace Mitchell, Timothy Beukelman

Published in: Pediatric Rheumatology | Issue 1/2019

Login to get access

Abstract

Background

Evidence remains contradictory regarding second-line therapy in patients with Kawasaki disease (KD) refractory to initial intravenous immunoglobulin (IVIg). The objective of this study aims to evaluate the efficacy and safety of three treatments [i.e. a second IVIg infusion, methylprednisolone (IVMP), and infliximab (IFX)] in patients with refractory KD.

Methods

A systematic search of PubMed, Embase, Cochrane, and ClinicalTrials.gov using predefined MeSH terms was performed from 1990 through 2017. Relevance screening was performed by two independent reviewers. Inclusion criteria included English-only, original clinical data. Eight studies met the inclusion criteria. Fever resolution, coronary lesions, and adverse event outcomes were extracted and pooled for analysis.

Results

Of the 388 patients included from the 8 studies analyzed, a majority received a second IVIg dose (n = 263, 68%). Fever resolution was comparable between IVIg (72%) and IVMP (73%). IFX (88%) significantly increased fever resolution by approximately 20% compared to IVIg re-dose (RR 1.2; [95% CI: 1.1–1.4]; p = 0.03) and IVMP (RR 1.2; [95% CI: 1.0–1.5]; p = 0.04). Clinical significance of differences in coronary outcomes remains unclear.

Conclusions

This combined analysis was limited due to variability in design and data reporting methods between the studies and risk of bias. In the absence of a clinical trial, IFX monotherapy as second-line treatment should be considered in patients who fail to respond to initial IVIg. This conclusion is based on a systematic review of the literature with pooled outcome data analysis suggesting IFX is more effective in fever resolution compared to a second IVIg dose and IVMP.
Literature
1.
2.
go back to reference Marrani E, Burns JC, Cimaz R. How should we classify Kawasaki disease? Front Immunol. 2018;9:2974.CrossRef Marrani E, Burns JC, Cimaz R. How should we classify Kawasaki disease? Front Immunol. 2018;9:2974.CrossRef
3.
go back to reference Callinan LS, Holman RC, Vugia DJ, Schonberger LB, Belay ED. Kawasaki disease hospitalization rate among children younger than 5 years in California, 2003-2010. Pediatr Infect Dis J. 2014;33(7):781–3.CrossRef Callinan LS, Holman RC, Vugia DJ, Schonberger LB, Belay ED. Kawasaki disease hospitalization rate among children younger than 5 years in California, 2003-2010. Pediatr Infect Dis J. 2014;33(7):781–3.CrossRef
4.
go back to reference McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term Management of Kawasaki Disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927–e99.CrossRef McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term Management of Kawasaki Disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927–e99.CrossRef
5.
go back to reference Newburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, Duffy CE, et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. 1986;315(6):341–7.CrossRef Newburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, Duffy CE, et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. 1986;315(6):341–7.CrossRef
6.
go back to reference Research Committee on Kawasaki Disease. Report of Subcommittee on Standardization of Diagnostic Criteria and Reporting of Coronary Artery Lesions in Kawasaki Disease. Tokyo: Ministry of Health and Welfare; 1984. Research Committee on Kawasaki Disease. Report of Subcommittee on Standardization of Diagnostic Criteria and Reporting of Coronary Artery Lesions in Kawasaki Disease. Tokyo: Ministry of Health and Welfare; 1984.
7.
go back to reference Yellen ES, Gauvreau K, Takahashi M, Burns JC, Shulman S, Baker AL, et al. Performance of 2004 American Heart Association recommendations for treatment of Kawasaki disease. Pediatrics. 2010;125(2):e234–41.CrossRef Yellen ES, Gauvreau K, Takahashi M, Burns JC, Shulman S, Baker AL, et al. Performance of 2004 American Heart Association recommendations for treatment of Kawasaki disease. Pediatrics. 2010;125(2):e234–41.CrossRef
8.
go back to reference 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(12):1144–8.CrossRef 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(12):1144–8.CrossRef
9.
go back to reference Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRef Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRef
10.
go back to reference Furukawa T, Kishiro M, Akimoto K, Nagata S, Shimizu T, Yamashiro Y. Effects of steroid pulse therapy on immunoglobulin-resistant Kawasaki disease. Arch Dis Child. 2008;93(2):142–6.CrossRef Furukawa T, Kishiro M, Akimoto K, Nagata S, Shimizu T, Yamashiro Y. Effects of steroid pulse therapy on immunoglobulin-resistant Kawasaki disease. Arch Dis Child. 2008;93(2):142–6.CrossRef
11.
go back to reference Miura M, Ohki H, Yoshiba S, Ueda H, Sugaya A, Satoh M, et al. Adverse effects of methylprednisolone pulse therapy in refractory Kawasaki disease. Arch Dis Child. 2005;90(10):1096–7.CrossRef Miura M, Ohki H, Yoshiba S, Ueda H, Sugaya A, Satoh M, et al. Adverse effects of methylprednisolone pulse therapy in refractory Kawasaki disease. Arch Dis Child. 2005;90(10):1096–7.CrossRef
12.
go back to reference Miura M, Tamame T, Naganuma T, Chinen S, Matsuoka M, Ohki H. Steroid pulse therapy for Kawasaki disease unresponsive to additional immunoglobulin therapy. Paediatr Child Health. 2011;16(8):479–84.CrossRef Miura M, Tamame T, Naganuma T, Chinen S, Matsuoka M, Ohki H. Steroid pulse therapy for Kawasaki disease unresponsive to additional immunoglobulin therapy. Paediatr Child Health. 2011;16(8):479–84.CrossRef
13.
go back to reference Ogata S, Bando Y, Kimura S, Ando H, Nakahata Y, Ogihara Y, et al. The strategy of immune globulin resistant Kawasaki disease: a comparative study of additional immune globulin and steroid pulse therapy. J Cardiol. 2009;53(1):15–9.CrossRef Ogata S, Bando Y, Kimura S, Ando H, Nakahata Y, Ogihara Y, et al. The strategy of immune globulin resistant Kawasaki disease: a comparative study of additional immune globulin and steroid pulse therapy. J Cardiol. 2009;53(1):15–9.CrossRef
14.
go back to reference Son MB, Gauvreau K, Burns JC, Corinaldesi E, Tremoulet AH, Watson VE, et al. Infliximab for intravenous immunoglobulin resistance in Kawasaki disease: a retrospective study. J Pediatr. 2011;158(4):644–9 e1.CrossRef Son MB, Gauvreau K, Burns JC, Corinaldesi E, Tremoulet AH, Watson VE, et al. Infliximab for intravenous immunoglobulin resistance in Kawasaki disease: a retrospective study. J Pediatr. 2011;158(4):644–9 e1.CrossRef
15.
go back to reference Teraguchi M, Ogino H, Yoshimura K, Taniuchi S, Kino M, Okazaki H, et al. Steroid pulse therapy for children with intravenous immunoglobulin therapy-resistant Kawasaki disease: a prospective study. Pediatr Cardiol. 2013;34(4):959–63.CrossRef Teraguchi M, Ogino H, Yoshimura K, Taniuchi S, Kino M, Okazaki H, et al. Steroid pulse therapy for children with intravenous immunoglobulin therapy-resistant Kawasaki disease: a prospective study. Pediatr Cardiol. 2013;34(4):959–63.CrossRef
16.
go back to reference Youn Y, Kim J, Hong YM, Sohn S. Infliximab as the first retreatment in patients with Kawasaki disease resistant to initial intravenous immunoglobulin. Pediatr Infect Dis J. 2016;35(4):457–9.CrossRef Youn Y, Kim J, Hong YM, Sohn S. Infliximab as the first retreatment in patients with Kawasaki disease resistant to initial intravenous immunoglobulin. Pediatr Infect Dis J. 2016;35(4):457–9.CrossRef
17.
go back to reference Singh S, Sharma D, Suri D, Gupta A, Rawat A, Rohit MK. Infliximab is the new kid on the block in Kawasaki disease: a single-Centre study over 8 years from North India. Clin Exp Rheumatol. 2016;34(3 Suppl 97):S134–8.PubMed Singh S, Sharma D, Suri D, Gupta A, Rawat A, Rohit MK. Infliximab is the new kid on the block in Kawasaki disease: a single-Centre study over 8 years from North India. Clin Exp Rheumatol. 2016;34(3 Suppl 97):S134–8.PubMed
18.
go back to reference Chan H, Chi H, You H, Wang M, Zhang G, Yang H, et al. Indirect-comparison meta-analysis of treatment options for patients with refractory Kawasaki disease. BMC Pediatr. 2019;19(1):158.CrossRef Chan H, Chi H, You H, Wang M, Zhang G, Yang H, et al. Indirect-comparison meta-analysis of treatment options for patients with refractory Kawasaki disease. BMC Pediatr. 2019;19(1):158.CrossRef
19.
go back to reference Booth A, Harper L, Hammad T, Bacon P, Griffith M, Levy J, et al. Prospective study of TNFalpha blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol. 2004;15(3):717–21.CrossRef Booth A, Harper L, Hammad T, Bacon P, Griffith M, Levy J, et al. Prospective study of TNFalpha blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol. 2004;15(3):717–21.CrossRef
20.
go back to reference Umazume A, Kezuka T, Usui Y, Suzuki J, Goto H. Evaluation of efficacy of infliximab for retinal vasculitis and extraocular symptoms in Behcet disease. Jpn J Ophthalmol. 2018;62(3):390–7.CrossRef Umazume A, Kezuka T, Usui Y, Suzuki J, Goto H. Evaluation of efficacy of infliximab for retinal vasculitis and extraocular symptoms in Behcet disease. Jpn J Ophthalmol. 2018;62(3):390–7.CrossRef
21.
go back to reference Hu P, Jiang GM, Wu Y, Huang BY, Liu SY, Zhang DD, et al. TNF-alpha is superior to conventional inflammatory mediators in forecasting IVIG nonresponse and coronary arteritis in Chinese children with Kawasaki disease. Clin Chim Acta. 2017;471:76–80.CrossRef Hu P, Jiang GM, Wu Y, Huang BY, Liu SY, Zhang DD, et al. TNF-alpha is superior to conventional inflammatory mediators in forecasting IVIG nonresponse and coronary arteritis in Chinese children with Kawasaki disease. Clin Chim Acta. 2017;471:76–80.CrossRef
22.
go back to reference Hui-Yuen JS, Duong TT, Yeung RS. TNF-alpha is necessary for induction of coronary artery inflammation and aneurysm formation in an animal model of Kawasaki disease. J Immunol. 2006;176(10):6294–301.CrossRef Hui-Yuen JS, Duong TT, Yeung RS. TNF-alpha is necessary for induction of coronary artery inflammation and aneurysm formation in an animal model of Kawasaki disease. J Immunol. 2006;176(10):6294–301.CrossRef
23.
go back to reference Lin CY, Lin CC, Hwang B, Chiang BN. Cytokines predict coronary aneurysm formation in Kawasaki disease patients. Eur J Pediatr. 1993;152(4):309–12.CrossRef Lin CY, Lin CC, Hwang B, Chiang BN. Cytokines predict coronary aneurysm formation in Kawasaki disease patients. Eur J Pediatr. 1993;152(4):309–12.CrossRef
24.
go back to reference Matsubara T, Furukawa S, Yabuta K. Serum levels of tumor necrosis factor, interleukin 2 receptor, and interferon-gamma in Kawasaki disease involved coronary-artery lesions. Clin Immunol Immunopathol. 1990;56(1):29–36.CrossRef Matsubara T, Furukawa S, Yabuta K. Serum levels of tumor necrosis factor, interleukin 2 receptor, and interferon-gamma in Kawasaki disease involved coronary-artery lesions. Clin Immunol Immunopathol. 1990;56(1):29–36.CrossRef
25.
go back to reference Tremoulet AH, Jain S, Jaggi P, Jimenez-Fernandez S, Pancheri JM, Sun X, et al. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet. 2014;383(9930):1731–8.CrossRef Tremoulet AH, Jain S, Jaggi P, Jimenez-Fernandez S, Pancheri JM, Sun X, et al. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet. 2014;383(9930):1731–8.CrossRef
Metadata
Title
Comparison of second-line therapy in IVIg-refractory Kawasaki disease: a systematic review
Authors
Courtney B. Crayne
Chace Mitchell
Timothy Beukelman
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2019
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-019-0380-z

Other articles of this Issue 1/2019

Pediatric Rheumatology 1/2019 Go to the issue