www.thelancet.com/child-adolescent Vol 2 December 2018 855 Articles Lancet Child Adolesc Health 2018; 2: 855–62 Published Online October 15, 2018 http://dx.doi.org/10.1016/ S2352-4642(18)30293-1 See Comment page 840 *Collaborators are listed at the end of this paper Department of Cardiology (K Miyata MD, M Miura MD), Clinical Research Support Center (T Kaneko MS, Y Morikawa MD), and Department of General Pediatrics (H Sakakibara MD, T Matsushima MD), Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan; Department of Pediatrics, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan (M Misawa MD); Department of Pediatrics, Saiseikai Utsunomiya Hospital, Tochigi, Japan (T Takahashi MD); Department of Pediatrics, National Hospital Organization Saitama National Hospital, Saitama, Japan (M Nakazawa MD); Department of Pediatrics, Saitama City Hospital, Saitama, Japan (T Tamame MD); Department of Pediatrics, Kawasaki Municipal Hospital, Kanagawa, Japan (T Tsuchihashi MD); Department of Pediatrics, Yokohama Municipal Citizen’s Hospital, Kanagawa, Japan (Y Yamashita MD); Department of Pediatrics, Tama-Hokubu Medical Center, Tokyo, Japan (T Obonai MD); Department of Pediatrics, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan (M Chiga MD); Department of Pediatrics, Ota Memorial Hospital, Gunma, Japan (N Hori MD); Department of Pediatrics, National Hospital Organization Tokyo Medical Center, Tokyo, Japan (O Komiyama MD); and Department of Pediatrics, Keio University School of Efficacy and safety of intravenous immunoglobulin plus prednisolone therapy in patients with Kawasaki disease (Post RAISE): a multicentre, prospective cohort study Koichi Miyata, Tetsuji Kaneko, Yoshihiko Morikawa, Hiroshi Sakakibara, Takahiro Matsushima, Masahiro Misawa, Tsutomu Takahashi, Maki Nakazawa, Takuya Tamame, Takatoshi Tsuchihashi, Yukio Yamashita, Toshimasa Obonai, Michiko Chiga, Naoaki Hori, Osamu Komiyama, Hiroyuki Yamagishi, Masaru Miura, on behalf of the Post RAISE group* Summary Background The RAISE study showed that additional prednisolone improved coronary artery outcomes in patients with Kawasaki disease at high risk of intravenous immunoglobulin (IVIG) resistance. However, no studies have been done to test the steroid regimen used in the RAISE study. We therefore aimed to verify the efcacy and safety of primary IVIG plus prednisolone. Methods We did a multicentre, prospective cohort study at 34 hospitals in Japan. We included patients diagnosed with Kawasaki disease according to the Japanese diagnostic criteria, and excluded those who were treated at other hospitals before being transferred to a participating hospital. Patients who were febrile at diagnosis received primary IVIG (2 g/kg per 24 h) and oral aspirin (30 mg/kg per day) until the fever resolved, followed by oral aspirin (5 mg/kg per day) for 2 months after Kawasaki disease onset. We stratifed patients using the Kobayashi score into predicted IVIG non- responders (Kobayashi score ≥5) or predicted IVIG responders (Kobayashi score <5). For predicted non-responders, each hospital independently decided whether to add prednisolone (intravenous injection of 2 mg/kg per day for 5 days) to the primary IVIG treatment, according to their respective treatment policy, and we further divided these patients based on the primary treatment received. The primary endpoint was the incidence of coronary artery abnormalities determined by two-dimensional echocardiography at 1 month after the primary treatment in predicted non-responders treated with primary IVIG plus prednisolone. Coronary artery abnormalities were defned according to the criteria of the Japanese Ministry of Health and Welfare and of the American Heart Association (AHA). This study is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000007133. Findings From July 1, 2012, to June 30, 2015, we enrolled 2628 patients with Kawasaki disease, of whom 724 (27∙6%) were predicted IVIG non-responders who received IVIG plus prednisolone as primary treatment. 132 (18·2%) of 724 patients did not respond to primary treatment. Among patients with complete data, coronary artery abnormalities were present in 40 (incidence rate 5·9%, 95% CI 4·3–8·0) of 676 patients according to the AHA criteria or in 26 (3·8%, 2·5–5·6) of 677 patients according to the Japanese criteria. Serious adverse events were reported in 12 (1·7%) of 724 patients treated with primary IVIG plus prednisolone; two of these patients had hypertension and bacteraemia that was probably related to prednisolone. One patient died possibly due to severe infammation from the Kawasaki disease itself. Interpretation Primary IVIG plus prednisolone therapy in this study had an efect similar to that seen in the RAISE study in reducing the non-response rate and decreasing the incidence of coronary artery abnormalities. A primary IVIG and prednisolone combination therapy might prevent coronary artery abnormalities and contribute to lowering medical costs. Funding Tokyo Metropolitan Government Hospitals and the Japan Kawasaki Disease Research Center. Copyright © 2018 Elsevier Ltd. All rights reserved. Introduction Kawasaki disease is an acute, autoinfammatory systemic vasculitis of unknown cause that leads to the formation of coronary artery abnormalities. Intravenous immuno- globulin (IVIG) and oral aspirin are the standard therapy for Kawasaki disease, but approximately 15–20% of patients do not respond to such treatment 1–3 and are at risk for coronary artery abnormalities even if they receive several rescue treatments. The indications for corticosteroid therapy in patients with Kawasaki disease are controversial. All studies that showed an increase in incidence of coronary artery abnormalities due to corticosteroids 4,5 were retrospectively done; therefore, these studies were unable to eliminate confounders by indication because these patients typically had increased disease severity. In several randomised controlled studies, primary IVIG combined with a corticosteroid decreased the incidence of coronary