Journal Article

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

Okuma, Yoshiaki, Honda, Takafumi, Takatsuki, Shinichi, Ogita, Satoko, Terauchi, Moe, Hirono, Keiichi, Ichida, Fukiko, Yanai, Masaaki, Suwabe, Shinichi, Nakayashiro, Mami, Saito, Naoki, Terai, Masaru, Ueno, Yasushi, Kato, Masataka, Ayusawa, Mamoru, Fuse, Shigeto, Masuda, Hiroshi, Takada, Nobuyuki, Onouchi, Yoshihiro, Suzuki, Hiroyuki, Takeuchi, Takashi, Nomura, Yuichi, Nishi, Natsuko, Hirai, Katsuki, Umeda, You, Minami, Hirotaka, Ishiguchi, Yukiko, Ono, Hiroshi, Okajima, Yoshitomo, Hashimura, Yuya, Nakano, Takeshi, Fujiwara, Tadami, Sato, Takatoshi, Yajima, Hideoki, Ohno, Naoki, Kurotobi, Shunji, Hata, Akira, Hanawa, Michiko, Ouchi, Kazunobu, Masuda, Kiminori, Kobayashi, Hironobu, Ooto, Hideyasu, Ozawa, Sayaka, Nakamura, Takahiro, Soga, Takashi, Uchiyama, Takamichi, Okizuka, You, Ishiguro, Akira, Yamamoto, Eiichi, Suenaga, Tomohiro, Nabeshima, Taisuke, Fujii, Yasuhisa, Takahiro, Nishihara, Aoyagi, Reiko, Kamada, Masahiro, Otsuki, Akio, Hanaoka, Hideki, Yasukawa, Kumi, Sato, Junichi, Okunushi, Kentaro, Ariga, Tadashi, Takefuta, Kiyotaka, Kitani, Yutaka, Kakimoto, Nobuyuki, Saji, Tsutomu, Ebata, Ryota, Higaki, Takashi

2019

Overview

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).

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Abnormalities / Calcium / Child / Child, Preschool / Clinical trials / Coronary artery / Coronary Vessel Anomalies - epidemiology / Coronary Vessel Anomalies - prevention & control / Coronary vessels / Cyclosporine - administration & dosage / Cyclosporine - therapeutic use / Disease prevention / Drug Resistance - immunology / Drug Therapy, Combination / Echocardiography / Evidence-based medicine / Female / Fever / Health risk assessment / Health Status Indicators / Humans / Illnesses / Immunoglobulins / Immunoglobulins, Intravenous - administration & dosage / Immunoglobulins, Intravenous - therapeutic use / Immunosuppressive Agents - therapeutic use / Incidence / Intravenous administration / Japan - epidemiology / Kawasaki disease / Lymphocytes / Male / Medical research / Mucocutaneous lymph node syndrome / Mucocutaneous Lymph Node Syndrome - diagnosis / Mucocutaneous Lymph Node Syndrome - drug therapy / Mucocutaneous Lymph Node Syndrome - genetics / Mucocutaneous Lymph Node Syndrome - immunology / NF-AT protein / Nuclear engineering / Nuclear safety / Pathogenesis / Patients / R&D / Randomization / Research & development / Risk / Transcription factors / Treatment Outcome / Veins & arteries