Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial.

Abstract

BACKGROUND:

Evidence indicates that corticosteroid therapy might be beneficial for the primary treatment of severe Kawasaki disease. We assessed whether addition of prednisolone to intravenous immunoglobulin with aspirin would reduce the incidence of coronary artery abnormalities in patients with severe Kawasaki disease.

METHODS:

We did a multicentre, prospective, randomised, open-label, blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec 2, 2010. Patients with severe Kawasaki disease were randomly assigned by a minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin group plus prednisolone 2 mg/kg per day given over 15 days after concentrations of C-reactive protein normalised). Patients and treating physicians were unmasked to group allocation. The primary endpoint was incidence of coronary artery abnormalities during the study period. Analysis was by intention to treat. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000000940.

FINDINGS:

We randomly assigned 125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to the intravenous immunoglobulin group. Incidence of coronary artery abnormalities was significantly lower in the intravenous immunoglobulin plus prednisolone group than in the intravenous immunoglobulin group during the study period (four patients [3%] vs 28 patients [23%]; risk difference 0·20, 95% CI 0·12-0·28, p<0·0001). Serious adverse events were similar between both groups: two patients had high total cholesterol and one neutropenia in the intravenous immunoglobulin plus prednisolone group, and one had high total cholesterol and another non-occlusive thrombus in the intravenous immunoglobulin group.

INTERPRETATION:

Addition of prednisolone to the standard regimen of intravenous immunoglobulin improves coronary artery outcomes in patients with severe Kawasaki disease in Japan. Further study of intensified primary treatment for this disease in a mixed ethnic population is warranted.

FUNDING:

Japanese Ministry of Health, Labour and Welfare.

• Authors: Tohru Kobayashi, Tsutomu Saji, Tetsuya Otani, Kazuo Takeuchi, Tetsuya Nakamura, Hirokazu Arakawa, Taichi Kato, Toshiro Hara, Kenji Hamaoka, Shunichi Ogawa, Masaru Miura, Yuichi Nomura, Shigeto Fuse, Fukiko Ichida, Mitsuru Seki, Ryuji Fukazawa, Chitose Ogawa, Kenji Furuno, Hirohide Tokunaga, Shinichi Takatsuki, Shinya Hara, Akihiro Morikawa, RAISE study group investigators
• Journal: Lancet (London, England) (Lancet) Vol. 379 Issue 9826 Pg. 1613-20 (Apr 28 2012) ISSN: 1474-547X [Electronic] England
• PMID: 22405251 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Immunoglobulins
• Prednisolone
• Aspirin

Topics

• Anti-Inflammatory Agents (therapeutic use)
• Aspirin (therapeutic use)
• Child, Preschool
• Coronary Artery Disease (prevention & control)
• Coronary Vessel Anomalies (prevention & control)
• Drug Therapy, Combination
• Female
• Humans
• Immunoglobulins (therapeutic use)
• Infant
• Male
• Mucocutaneous Lymph Node Syndrome (drug therapy)
• Prednisolone (therapeutic use)
• Prospective Studies