Infliximab for the Treatment of Refractory Kawasaki Disease: A Nationwide Survey in Japan - 08/12/17

Doi : 10.1016/j.jpeds.2017.10.013

Hiroshi Masuda, MD ^1,^2,^{*
Contributed equally.}, Tohru Kobayashi, MD ^3,^*^{*
Contributed equally.} , Akira Hachiya, MD ⁴, Yasutaka Nakashima, MD ⁵, Hiroyuki Shimizu, MD ⁶, Tomo Nozawa, MD ², Yoshihito Ogihara, MD ⁷, Shuichi Ito, MD ^2,⁸, Shinichi Takatsuki, MD ⁹, Nobuyuki Katsumata, MD ¹⁰, Yasuo Suzuki, MD ¹¹, Satoshi Takenaka, MD ¹², Keiichi Hirono, MD ¹³, Tomio Kobayashi, MD ¹⁴, Hiroshi Suzuki, MD ¹⁵, Eisuke Suganuma, MD ¹⁶, Kei Takahashi, MD ¹⁷, Tsutomu Saji, MD ¹⁸
Committee of Survey on Infliximab use for Kawasaki disease^19,^†
List of additional members of the Japan Society of Kawasaki Disease Research Committee on Infliximab Use is available at www.jpeds.com (Appendix 1).
Satoshi Matsuzaki, MD ²⁰, Shoko Yamazaki, MD ²⁰, Kazuyuki Ikeda, MD ²¹, Takuma Hara, MD ²², Taichi Kanetaka, MD ²³, Toshitaka Kizawa, MD ²³, Masako Kikuchi, MD ²³, Ryoki Hara, MD ²³, Kentaro Fujii, MD ²³, Mayu Takahashi, MD ²³, Kaori Sonoda, MD ²³, Tomokuni Yoshihashi, MD ²³, Tomoyuki Imagawa, MD ²³, Kazuko Yamazaki, MD ²³, Takasuke Ebato, MD ²⁴, Shinji Oana, MD ²⁵, Ayako Murase, MD ²⁵, Shinichiro Sakaki, MD ²⁵, Takeshi Fujimoto, MD ²⁵, Yoshihiko Saito, MD ²⁵, Ryota Shirai, MD ²⁵, Ichiro Takeuchi, MD ²⁵, Kazuyuki Naoi, MD ²⁶, Yasushi Kenmotsu, MD ²⁶, Chiaki Goto ²⁶, Hiroaki Kise, MD ²⁷, Seigo Okada, MD ²⁸, Sayuri Kishimoto, MD ²⁹, Utako Oba, MD ²⁹, Sayaka Ozawa, MD ³⁰, Mitsuru Seki, MD ³¹, Tesshu Odagiri, MD ³², Junko Shiono, MD ³³, Kiyoshi Nagumo, MD ³⁴, Mitsuaki Kimura, MD ³⁵, Muneo Yoshibayashi, MD ³⁶, Norihisa Horita, MD ³⁷, Tatsuo Tsuboi, MD ³⁸, Tomoyo Matsubara, MD ³⁹, Satoshi Hara, MD ³⁹, Taku Ishii, MD ⁴⁰, Susumu Hosokawa, MD ⁴⁰, Takayuki Kishi, MD ⁴¹, Ryuji Fukazawa, MD ⁴², Shunichi Ogawa, MD ⁴², Miho Ohshima, MD ⁴³, Hideo Fukunaga, MD ⁴⁴, Hiroko Kouzan, MD ⁴⁵, Tomoko Ichihara, MD ⁴⁵, Kunio Hashimoto, MD ⁴⁶, Hirohide Tokunaga, MD ⁴⁷, Hiroshi Suzuki, MD ⁴⁸, Satoru Iwashima, MD ⁴⁹, Kiyoshi Hamahira, MD ⁵⁰, Yukiko Ishiguchi, MD ⁵¹, Mayumi Kajino, MD ⁵², Kanta Kishi, MD ⁵³, Noriko Nagai, MD ⁵⁴, Shigeru Ito, MD ⁵⁵, Hirotaro Ogino, MD ⁵⁶, Eriko Amaya, MD ⁵⁷, Hiraku Doi, MD ⁵⁸, Kenji Waki, MD ⁵⁹, Taisuke Shiraishi, MD ⁶⁰, Takashi Iwai, MD ⁶¹, Tetsuji Sato, MD ⁶², Katsumi Akimoto, MD ⁶³, Takashi Soga, MD ⁶⁴, Hiroyuki Naito, MD ⁶⁵, Makiko Aihara, MD ⁶⁶, Yutaka Fukuda, MD ⁶⁷, Kazuo Imagawa, MD ⁶⁸, Takeshi Shiba, MD ⁶⁹, Shigenobu Matsuki, MD ⁷⁰, Masaru Miura, MD ⁷¹, Tooru Araki, MD ⁷², Hideto Furuyama, MD ⁷³, Takeshi Naito, MD ⁷⁴, Tomoyuki Miyamoto, MD ⁷⁵
²⁰ Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
²¹ Department of Pediatrics, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Fukuoka, Japan
²² Children's Medical Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
²³ Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
²⁴ Division of Pediatric Nephrology and Rheumatology, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
²⁵ Department of General Pediatrics and Interdisciplinary Medicine, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
²⁶ Department of Pediatrics, Toho University, Medical Center Omori Hospital, Ota-ku, Tokyo, Japan
²⁷ Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
²⁸ Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
²⁹ Department of Pediatrics, Japan Community Healthcare Organization (JCHO), Kyusyu Hospital, Kitakyushu, Fukuoka, Japan
³⁰ Department of Pediatrics, Graduate School of Medicine, University of Toyama, Toyama, Toyama, Japan
³¹ Division of Cardiology, Gunma Children's Medical Center, Shibukawa, Gunma, Japan
³² Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Yamagata, Japan
³³ Division of Cardiology, Ibaraki Children's Hospital, Mito, Japan
³⁴ Department of Pediatrics, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan
³⁵ Department of Allergy and Clinical Immunology, Shizuoka Children's Hospital, Shizuoka, Shizuoka, Japan
³⁶ Department of Pediatrics, Kindai University Nara Hospital, Ikoma, Nara, Japan
³⁷ Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan
³⁸ Department of Pediatrics, Dokkyo Medical University School of Medicine, Mibu-machi, Shimotsuga-gun, Tochigi, Japan
³⁹ Department of Pediatrics, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
⁴⁰ Department of Pediatrics, Tokyo Medical And Dental University Hospital Faculty of Medicine, Bunkyo-ku, Tokyo, Japan
⁴¹ Department of Pediatrics, Tokyo Women's Medical University Hospital, Shinjuku-ku, Tokyo, Japan
⁴² Department of Pediatrics, Nippon Medical School Hospital, Bunkyo-ku, Tokyo, Japan
⁴³ Department of Pediatrics, Sapporo Tokushukai Hospital, Sapporo, Hokkaido, Japan
⁴⁴ Department of Pediatrics, Juntendo University Nerima Hospital, Nerima-ku, Tokyo, Japan
⁴⁵ Department of Pediatrics, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan
⁴⁶ Department of Pediatrics, Nagasaki University Hospital, Nagasaki, Nagasaki, Japan
⁴⁷ Department of Pediatrics, Nagoya Memorial Hospital, Nagoya, Aichi, Japan
⁴⁸ Department of Pediatrics, Niigata University Medical and Dental Hospital, Niigata, Niigata, Japan
⁴⁹ Department of Pediatrics, Hamamatsu University Hospital, Hamamatsu, Shizuoka, Japan
⁵⁰ Department of Pediatrics, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan
⁵¹ Department of Pediatrics, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Hiroshima, Japan
⁵² Department of Pediatrics, Asahikawa Kosei General Hospital, Asahikwa, Hokkaido, Japan
⁵³ Department of Pediatrics, Osaka Medical College Hospital, Takatsuki, Osaka, Japan
⁵⁴ Department of Pediatrics, Okazaki City Hospital, Okazaki, Aichi, Japan
⁵⁵ Department of Pediatrics, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
⁵⁶ Department of Pediatrics, Kansai Medical University Kori Hospital, Hirakata, Osaka, Japan
⁵⁷ Department of Pediatrics, Kyoto City Hospital, Kyoto, Kyoto, Japan
⁵⁸ Department of Pediatrics, Kyoto University Hospital, Kyoto, Kyoto, Japan
⁵⁹ Department of Pediatrics, Kurashiki Central Hospital, Kurashiki, Okayama, Japan
⁶⁰ Department of Pediatrics, Hata Kenmin Hospital, Sukumo, Kochi, Japan
⁶¹ Department of Pediatrics, Hakodate Goryoukaku Hospital, Hakodate, Hokkaido, Japan
⁶² Department of Pediatrics, Hospital of the University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan
⁶³ Department of Pediatrics, Juntendo University Hospital, Bunkyo-ku, Tokyo Japan
⁶⁴ Department of Pediatrics, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa, Japan
⁶⁵ Department of Pediatrics, Chitose City Hospital, Chitose, Hokkaido, Japan
⁶⁶ Department of Pediatrics, Saiseikai Kawaguchi General Hospital, Kawaguchi, Saitama, Japan
⁶⁷ Department of Pediatrics, Takeda General Hospital, Kyoto, Kyoto,Japan
⁶⁸ Department of Pediatrics, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
⁶⁹ Department of Pediatrics, Tenri Hospital, Tenri, Nara, Japan
⁷⁰ Department of Pediatrics, KKR Tohoku Kosai Hospital, Sendai, Miyagi, Japan
⁷¹ Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo,Japan
⁷² Department of Pediatrics, National Hospital Organization Fukuyama Medical Center, Fukuyama, Hiroshima, Japan
⁷³ Department of Pediatrics, Japan Community Health care Organization Hokkaido Hospital, Sapporo, Hokkaido, Japan
⁷⁴ Department of Pediatrics, Matsushita Memorial Hospital, Moriguchi, Osaka, Japan
⁷⁵ Department of Pediatrics, Yokosuka General Hospital Uwamachi, Yokosuka, Kanagawa,Japan

¹ Department of General Pediatrics and Interdisciplinary Medicine, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
² Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Kanagawa, Japan
³ Division of Clinical Research Planning, Department of Development Strategy, Center for Clinical Research and Development, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
⁴ Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
⁵ Department of Pediatrics, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Fukuoka, Japan
⁶ Children's Medical Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
⁷ Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
⁸ Division of Pediatric Nephrology and Rheumatology, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan
⁹ Department of Pediatrics, Toho University, Medical Center Omori Hospital, Ota-ku, Tokyo, Japan
¹⁰ Department of Pediatrics, Faculty of Medicine University of Yamanashi, Chuo, Yamanashi, Japan
¹¹ Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
¹² Department of Pediatrics, Japan Community Healthcare Organization (JCHO), Kyusyu Hospital, Kitakyushu, Fukuoka, Japan
¹³ Department of Pediatrics, Graduate School of Medicine, University of Toyama, Toyama, Toyama, Japan
¹⁴ Division of Cardiology, Gunma Children's Medical Center, Shibukawa, Gunma, Japan
¹⁵ Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Yamagata, Japan
¹⁶ Division of Infectious Diseases and Immunology, Saitama Children's Medical Center, Saitama, Saitama, Japan
¹⁷ Department of Pathology, Toho University Ohashi Medical Center, Shibuya-ku, Tokyo, Japan
¹⁸ Advanced and Integrated Cardiovascular Research Course in the Young and Adolescence, Ota-ku, Toho University, Tokyo, Japan
¹⁹ Japan Society of Kawasaki Disease, Tokyo, Japan

^*Reprint requests: Tohru Kobayashi, MD, Division of Clinical Research Planning, Department of Development Strategy, Center for Clinical Research and Development, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.Division of Clinical Research PlanningDepartment of Development StrategyCenter for Clinical Research and DevelopmentNational Center for Child Health and Development2-10-1 OkuraSetagaya-kuTokyo157-8535Japan

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Abstract

Objective

To assess the safety and efficacy of infliximab (IFX) for the treatment of patients with Kawasaki disease (KD).

Study design

This was a nationwide survey of 274 Japanese institutions exploring how IFX was used to treat patients with KD. The patients' sex, age, treatment course, pre- and post-IFX therapy blood test results, coronary artery lesions (CALs), and adverse events (AEs) were evaluated.

Results

We analyzed 434 patients with KD who received IFX between March 2005 and November 2014. The median age at onset was 33 months (range 1-138), and 66 patients (15.2%) were under 1 year old. In all cases, IFX was administered as additional treatment. The median days of illness at the initiation of IFX was 9 days. In 275 patients (63.4%), IFX was administered as third-line treatment, and in 106 patients (24.4%), IFX was administered as fourth-line treatment. Single dose IFX 5 mg/kg was administered to 412 patients (94.9%). After IFX, 363 patients (83.6%) became afebrile within 2 days, and the white blood cell count, percentage of neutrophils, and serum C-reactive protein levels significantly decreased (P < .001), although 119 patients (27.4%) received additional treatment. Before IFX, 132 patients (30.4%) had already developed CALs. In patients without CALs before IFX, 31 patients (10.3%) newly developed CAL after IFX, whereas 32 patients (24.2%) with CAL before IFX showed increased CAL severity. Eighty AEs were observed in 69 patients (15.9%); however, serious AEs were few and reversible.