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1 Supplementary Online Content Chen S, Dong Y, Wang J, et al. Coronary artery complication in Kawasaki disease and the importance of early intervention (the International CAKE Study): a systematic review and meta-anlayis. JAMA Pediatr. Published October 17, doi: /jamapediatrics efigure 1. The study selection flow diagram efigure 2. Meta-regression of days of illness before corticosteroids intervention on Log OR of the effect of corticosteroids on CAA efigure 3. Meta-analysis for days of fever after intervention efigure 4. Meta-analysis for adverse events etable 1. Studies excluded from our meta-analysis after reassessment of full-text articles etable 2. Assessment of methodological quality of included studies etable 3. Results of meta-regression analysis based on baseline variables etable 4. Summary of secondary outcome data of included studies This supplementary material has been provided by the authors to give readers additional information about their work.

2 The study selection process followed the PRISMA guideline for systematic review [10].

3 efigure 2: Meta-regression of days of illness before corticosteroids intervention on Log OR of the effect of corticosteroids on CAA. *In the meta-regression graph, the circle size reflected the weight a study obtained by a random-effects model in this meta-regression.

4 efigure 3. Meta-analysis for duration (days) of fever after inervention.

5 efigure 4. Meta-analysis for adverse events.

6 etable 1 Studies excluded from our meta-analysis after reassessment of full-text articles. Study Reasons Wright DA, Newburger JW, Baker A, Sundel RP. Treatment of immune Not globulin-resistant Kawasaki disease with pulsed doses of corticosteroids. J comparative Pediatr 1996;128: study Lang BA, Yeung RS, Oen KG, Malleson PN, Huber AM, Riley M, Ebbeson R, Ramsey SE, Laxer RM, Silverman ED, McCrindle BW, Ratnapalan S, Feldman BM. Corticosteroid treatment of refractory Kawasaki disease. J Rheumatol 2006;33: Alexopoulos A, Vekiou A, Lycopoulou L, Tavena A, Lagona E, Kakourou T. Kawasaki disease in Greek children: a retrospective study. J Eur Acad Dermatol Venereol 2013;27(5):580-8 Jibiki T, Kato I, Shiohama T, Abe K, Anzai S, Takeda N, Yamaguchi K, Kanazawa M, Kurosaki T. Intravenous immune globulin plus corticosteroids in refractory Kawasaki disease. Pediatr Int 2011;53: Millar K, Manlhiot C, Yeung RS, Somji Z, McCrindle BW. Corticosteroid administration for patients with coronary artery aneurysms after Kawasaki disease may be associated with impaired regression. Int J Cardiol 2012;154:9-13. Not comparative study Not comparative study Not to report the incidence of CAA Complicated patients allocation

7 etable 2 Study Kobayas hi 2013 [30] Teraguch i 2013 [29] Kobayas hi 2012 [28] Ogata 2012 [27] Kobayas hi-i 2009 [26] unselected patients Kobayas hi-ii 2009 [26] high-risk patients Okada 2009 [25] Ogata 2009 [24] Miura 2008 [23] Furukaw a 2008 [22] Newburg er 2007 [21] Inoue 2006 [20] Study Assessment of methodological quality of included studies. Random ized trial? Clear definitio n of study populati on? Clear definit ion of outco me? Blinde d assess ment of outcom e? Compl ete outco me data? Free of selectiv e reporti ng? Other potenti al bias controll ed? No Yes Yes No Yes Yes Yes 5 No Yes Yes No Yes Yes Yes 5 Yes Yes Yes Yes Yes Yes Yes 7 Yes Yes Yes Yes Yes Yes Yes 7 Yes Yes Yes NR Yes Yes Yes 6 Yes Yes Yes Yes Yes Yes Yes 7 Random ized trial? Clear definitio n of study Clear definit ion of outco Blinde d assess ment of Compl ete outco me Free of selectiv e reporti Other potenti al bias controll sco re sco re

8 populati me? outcom data? ng? ed? on? e? Jibiki Yes Yes Yes NR Yes Yes Yes [19] Okada 2003 [18] Sundel Yes Yes Yes Yes Yes Yes Yes [17] Hashino Yes Yes Yes Yes Yes Yes Yes [16] Shinohar a 1999 [15] NR= not reported The full score of the methodological quality was 7 points; studies with 5 or more points were considered as studies with medium-high quality.

9 etable 3 Results of meta-regression analysis based on baseline variables. Baseline Studies Regression parameters variables included in Slope Lower limit Upper P value regression (N) estimate limit Sample size (n) Mean age (years) Gender (male %) Mean duration of illness before corticosteroids intervention (days)

10 etable 4 Summary of secondary outcome data of included studies Study name Sample size(n) (CORT+IVIG or Res CORT group / IVIG group) Duration of fever after intervention (days) (estimated by Mean±SD) CORT+IVIG or Res CORT group IVIG group Kobayashi /140 NA NA [30] Teraguchi 14/27 NA NA 2013 [29] Kobayashi 121/121 1±0 2± [28] Ogata 22/26 1±0.5 7± [27] Kobayashi-I 2009 [26] unselected patients 110/896 NA NA Kobayashi-II 2009 [26] high-risk patients 48/298 NA NA Okada 62/32 NA NA 2009 [25] Ogata 13/14 1±1.3 3± [24] Miura 7/8 P=0.01 P= [23] Furukawa 44/19 NA NA 2008 [22] Newburger 101/98 0±0.17 1± [21] Inoue 90/88 0.6± ± [20] Jibiki 46/46 1±2.75 2± [19] Okada 14/18 0.3± ± [18] Sundel 18/21 1.0± ± [17] Hashino 9/8 1.4± ± [16] Shinohara 62/25 0.6± ± [15] Pooled results 861/ ± ±2.6 Res: rescue; CORT: corticosteroids, NA: not available