Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial

被引：143

作者：

Hamada, Hiromichi ^{[3
,4
]}

Suzuki, Hiroyuki ^{[5
]}

Onouchi, Yoshihiro ^{[1
]}

Ebata, Ryota ^{[2
]}

Terai, Masaru ^{[4
]}

Fuse, Shigeto ^{[6
]}

Okajima, Yoshitomo ^{[7
]}

Kurotobi, Shunji ^{[8
]}

Hirai, Katsuki ^{[9
]}

Soga, Takashi ^{[10
]}

Ishiguchi, Yukiko ^{[11
]}

Okuma, Yoshiaki ^{[12
]}

Takada, Nobuyuki ^{[13
]}

Yanai, Masaaki ^{[14
]}

Sato, Junichi ^{[15
]}

Nakayashiro, Mami ^{[16
,17
]}

Ayusawa, Mamoru ^{[18
]}

Yamamoto, Eiichi ^{[19
]}

Nomura, Yuichi ^{[20
]}

Hashimura, Yuya ^{[21
]}

Ouchi, Kazunobu ^{[22
]}

Masuda, Hiroshi ^{[23
]}

Takatsuki, Shinichi ^{[24
]}

Hirono, Keiichi ^{[25
]}

Ariga, Tadashi ^{[26
]}

Higaki, Takashi ^{[27
]}

Otsuki, Akio ^{[28
]}

Terauchi, Moe ^{[29
]}

Aoyagi, Reiko ^{[29
]}

Sato, Takatoshi ^{[29
]}

Fujii, Yasuhisa ^{[29
]}

Fujiwara, Tadami ^{[29
]}

Hanaoka, Hideki ^{[29
]}

Hata, Akira ^{[1
]}

机构：

[1] Chiba Univ, Dept Publ Hlth, Chiba, Japan

[2] Chiba Univ, Dept Pediat, Chiba, Japan

[3] Chiba Univ, Grad Sch Med, Chiba, Japan

[4] Tokyo Womens Med Univ, Yachiyo Med Ctr, Dept Pediat, Chiba, Japan

[5] Wakayama Med Univ Med, Dept Pediat, Wakayama, Japan

[6] NTT Sapporo Med Ctr, Dept Pediat, Sapporo, Hokkaido, Japan

[7] Chiba Cardiovasc Ctr, Dept Pediat, Chiba, Japan

[8] Oriono Clin, Sakai, Osaka, Japan

[9] Japanese Red Cross Kumamoto Hosp, Dept Pediat, Kumamoto, Japan

[10] Showa Univ, Northern Yokohama Hosp, Dept Pediat, Yokohama, Kanagawa, Japan

[11] Hiroshima City Hiroshima Citizens Hosp, Dept Pediat Cardiol, Hiroshima, Japan

[12] Natl Ctr Global Hlth & Med, Dept Pediat, Tokyo, Japan

[13] Kimitsu Chuo Hosp, Dept Pediat, Chiba, Japan

[14] Kumamoto Reg Med Ctr, Dept Pediat, Kumamoto, Japan

[15] Funabashi Municipal Med Ctr, Dept Pediat, Funabashi, Chiba, Japan

[16] Okinawa Prefectural Nanbu Med Ctr, Dept Pediat Cardiol, Okinawa, Japan

[17] Childrens Med Ctr, Okinawa, Japan

[18] Nihon Univ, Itabashi Hosp, Dept Pediat, Tokyo, Japan

[19] Ehime Prefectural Cent Hosp, Dept Pediat, Matsuyama, Ehime, Japan

[20] Kagoshima City Hosp, Dept Pediat, Kagoshima, Japan

[21] Takatsuki Gen Hosp, Dept Pediat, Osaka, Japan

[22] Kawasaki Med Sch Hosp, Dept Pediat, Okayama, Japan

[23] Natl Ctr Child Hlth & Dev, Dept Gen Pediat & Interdisciplinary Med, Tokyo, Japan

[24] Toho Univ, Dept Pediat, Tokyo, Japan

[25] Univ Toyama, Grad Sch Med, Dept Pediat, Toyama, Japan

[26] Hokkaido Univ Hosp, Dept Pediat, Sapporo, Hokkaido, Japan

[27] Ehime Univ, Grad Sch Med, Dept Reg Pediat & Perinatol, Matsuyama, Ehime, Japan

[28] Komatsu Municipal Hosp, Dept Pediat, Komatsu, Ishikawa, Japan

[29] Chiba Univ Hosp, Clin Res Ctr, Chiba, Japan

来源：

LANCET | 2019年 / 393卷 / 10176期

关键词：

SUSCEPTIBILITY; EPIDEMIOLOGY; GUIDELINES; THERAPY;

D O I：

10.1016/S0140-6736(18)32003-8

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities. Methods We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016. Eligible patients predicted to be at higher risk for intravenous immunoglobulin (IVIG) resistance were randomly assigned to IVIG plus ciclosporin (5 mg/ kg per day for 5 days; study treatment) or IVIG (conventional treatment) groups, stratified by risk score, age, and sex. The primary endpoint was incidence of coronary artery abnormalities using Japanese criteria during the 12-week trial, assessed in participants who received at least one dose of study drug and who visited the study institution at least once during treatment. This trial is registered to Center for Clinical Trials, Japan Medical Association, number JMA-IIA00174. Findings We enrolled 175 participants. One patient withdrew consent after enrolment and was excluded and one patient (in the study treatment group) was excluded from analysis because of lost echocardiography data. Incidence of coronary artery abnormalities was lower in the study treatment group than in the conventional treatment group (12 [14%] of 86 patients vs 27 [31%] of 87 patients; risk ratio 0.46; 95% CI 0.25-0.86; p=0.010). No difference was found in the incidence of adverse events between the groups (9% vs 7%; p=0.78). Interpretation Combined primary therapy with IVIG and ciclosporin was safe and effective for favourable coronary artery outcomes in Kawasaki disease patients who were predicted to be unresponsive to IVIG. Funding Japan Agency for Medical Research and Development (grant CCT-B-2503). Copyright (c) 2019 Elsevier Ltd. All rights reserved.

引用

页码：1128 / 1137

页数：10

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