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.
Child
Child, Preschool
Coronary Vessel Anomalies
/ epidemiology
Cyclosporine
/ administration & dosage
Drug Resistance
/ immunology
Drug Therapy, Combination
Female
Health Status Indicators
Humans
Immunoglobulins, Intravenous
/ administration & dosage
Immunosuppressive Agents
/ therapeutic use
Incidence
Japan
/ epidemiology
Male
Mucocutaneous Lymph Node Syndrome
/ diagnosis
Treatment Outcome
Journal
Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R
Informations de publication
Date de publication:
16 Mar 2019
16 Mar 2019
Historique:
received:
03
07
2018
revised:
07
08
2018
accepted:
21
08
2018
pubmed:
12
3
2019
medline:
9
5
2019
entrez:
12
3
2019
Statut:
ppublish
Résumé
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. 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. 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). 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. Japan Agency for Medical Research and Development (grant CCT-B-2503).
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
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
BACKGROUND
Japan Agency for Medical Research and Development (grant CCT-B-2503).
Identifiants
pubmed: 30853151
pii: S0140-6736(18)32003-8
doi: 10.1016/S0140-6736(18)32003-8
pii:
doi:
Substances chimiques
Immunoglobulins, Intravenous
0
Immunosuppressive Agents
0
Cyclosporine
83HN0GTJ6D
Types de publication
Clinical Trial, Phase III
Comparative Study
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1128-1137Investigateurs
Hiromichi Hamada
(H)
Takafumi Honda
(T)
Kumi Yasukawa
(K)
Katsuki Hirai
(K)
Nishihara Takahiro
(N)
Takashi Soga
(T)
Hideoki Yajima
(H)
Hideyasu Ooto
(H)
You Umeda
(Y)
Hiroyuki Suzuki
(H)
Takashi Takeuchi
(T)
Tomohiro Suenaga
(T)
Nobuyuki Kakimoto
(N)
Yukiko Ishiguchi
(Y)
Masahiro Kamada
(M)
Yoshiaki Okuma
(Y)
Nobuyuki Takada
(N)
Shinichi Suwabe
(S)
Masaaki Yanai
(M)
Yasushi Ueno
(Y)
Natsuko Nishi
(N)
Junichi Sato
(J)
Yuuko Saito
(Y)
Yutaka Kitani
(Y)
Mami Nakayashiro
(M)
Taisuke Nabeshima
(T)
Kiyotaka Takefuta
(K)
Mamoru Ayusawa
(M)
Takahiro Nakamura
(T)
Akiko Komori
(A)
Masataka Kato
(M)
Ryota Ebata
(R)
Naoki Saito
(N)
Kentaro Okunushi
(K)
Hironobu Kobayashi
(H)
Eiichi Yamamoto
(E)
Takeshi Nakano
(T)
Yuichi Nomura
(Y)
Kiminori Masuda
(K)
Yuya Hashimura
(Y)
Hirotaka Minami
(H)
Takamichi Uchiyama
(T)
You Okizuka
(Y)
Kazunobu Ouchi
(K)
Naoki Ohno
(N)
Satoko Ogita
(S)
Hiroshi Masuda
(H)
Hiroshi Ono
(H)
Akira Ishiguro
(A)
Shinichi Takatsuki
(S)
Tsutomu Saji
(T)
Fukiko Ichida
(F)
Keiichi Hirono
(K)
Sayaka Ozawa
(S)
Tadashi Ariga
(T)
Atsuhito Takeda
(A)
Gaku Izumi
(G)
Takashi Higaki
(T)
Akio Otsuki
(A)
Akira Hata
(A)
Hideki Hanaoka
(H)
Hiroyuki Suzuki
(H)
Masaru Terai
(M)
Hiromichi Hamada
(H)
Yoshihiro Onouchi
(Y)
Ryota Ebata
(R)
Moe Terauchi
(M)
Yasuhisa Fujii
(Y)
Takatoshi Sato
(T)
Reiko Aoyagi
(R)
Michiko Hanawa
(M)
Tadami Fujiwara
(T)
Shigeto Fuse
(S)
Yoshitomo Okajima
(Y)
Shunji Kurotobi
(S)
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Type : ErratumIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.