title: Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis under Treatment with Tocilizumab.
abstract: OBJECTIVE
  To identify macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA) undergoing tocilizumab (TCZ) treatment, and to confirm laboratory marker changes and responses to treatment in patients with MAS receiving TCZ.
  
  
  METHODS
  In Japan, 394 patients with sJIA were registered in an all-patient registry surveillance of TCZ as of January 15, 2012. TCZ (8 mg/kg) was administered every 2 weeks to patients with sJIA. MAS, hemophagocytic lymphohistiocytosis, or Epstein-Barr virus-associated hemophagocytic syndrome (EB-VAHS) was reported in 23 of these patients (25 events). The Safety Evaluation Committee of Tocilizumab for JIA reviewed these cases and clinically evaluated the data and laboratory findings using their own therapeutic experience. Events were categorized into 4 groups: definitive MAS, probable MAS, EB-VAHS, and non-MAS.
  
  
  RESULTS
  The committee's review revealed 3 events of definitive MAS in 3 patients, 12 events of probable MAS in 11 patients, 2 events of EB-VAHS in 2 patients, and 8 events of non-MAS in 8 patients. There were 2 patients who developed 2 events: 2 events in 1 patient were classified into definitive MAS and probable MAS, and 2 events in another patient were classified into probable MAS. In patients with definitive or probable MAS, common clinical manifestations and laboratory findings of MAS were observed. Changes in laboratory data observed in patients with EB-VAHS were similar to those observed in patients with MAS.
  
  
  CONCLUSIONS
  These results suggest that the clinical/laboratory features in the course of MAS appear to be similar among patients regardless of whether TCZ is administered. Similarities in the pathophysiological background of MAS and EB-VAHS were also suggested.
authors: From The Safety Evaluation Committee of Tocilizumab for JIA; Department of Pediatrics, Nippon Medical School; Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU) Graduate School of Medical and Dental Sciences; Chugai Pharmaceutical Co. Ltd., Tokyo; Department of Pediatrics, Yokohama City University School of Medicine, Kanagawa; Department of Pediatric Cardiology, Saitama Medical University International Medical Center, Saitama; Division of Rheumatology and Clinical Immunology, Jichi Medical School, Tochigi, Japan.S. Yokota, MD, PhD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Yokohama City University School of Medicine; Y. Itoh, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Nippon Medical School; T. Morio, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics and Developmental Biology, TMDU Graduate School of Medical and Dental Sciences; N. Sumitomo, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatric Cardiology, Saitama Medical University International Medical Center; K. Daimaru, BS, Chugai Pharmaceutical Co. Ltd.; S. Minota, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Division of Rheumatology and Clinical Immunology, Jichi Medical School. syokota@med.yokohama-cu.ac.jp.
authors: Shumpei
authors: S
authors: Yokota
authors: From The Safety Evaluation Committee of Tocilizumab for JIA; Department of Pediatrics, Nippon Medical School; Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU) Graduate School of Medical and Dental Sciences; Chugai Pharmaceutical Co. Ltd., Tokyo; Department of Pediatrics, Yokohama City University School of Medicine, Kanagawa; Department of Pediatric Cardiology, Saitama Medical University International Medical Center, Saitama; Division of Rheumatology and Clinical Immunology, Jichi Medical School, Tochigi, Japan.S. Yokota, MD, PhD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Yokohama City University School of Medicine; Y. Itoh, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Nippon Medical School; T. Morio, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics and Developmental Biology, TMDU Graduate School of Medical and Dental Sciences; N. Sumitomo, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatric Cardiology, Saitama Medical University International Medical Center; K. Daimaru, BS, Chugai Pharmaceutical Co. Ltd.; S. Minota, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Division of Rheumatology and Clinical Immunology, Jichi Medical School.
authors: Yasuhiko
authors: Y
authors: Itoh
authors: From The Safety Evaluation Committee of Tocilizumab for JIA; Department of Pediatrics, Nippon Medical School; Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU) Graduate School of Medical and Dental Sciences; Chugai Pharmaceutical Co. Ltd., Tokyo; Department of Pediatrics, Yokohama City University School of Medicine, Kanagawa; Department of Pediatric Cardiology, Saitama Medical University International Medical Center, Saitama; Division of Rheumatology and Clinical Immunology, Jichi Medical School, Tochigi, Japan.S. Yokota, MD, PhD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Yokohama City University School of Medicine; Y. Itoh, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Nippon Medical School; T. Morio, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics and Developmental Biology, TMDU Graduate School of Medical and Dental Sciences; N. Sumitomo, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatric Cardiology, Saitama Medical University International Medical Center; K. Daimaru, BS, Chugai Pharmaceutical Co. Ltd.; S. Minota, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Division of Rheumatology and Clinical Immunology, Jichi Medical School.
authors: Tomohiro
authors: T
authors: Morio
authors: From The Safety Evaluation Committee of Tocilizumab for JIA; Department of Pediatrics, Nippon Medical School; Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU) Graduate School of Medical and Dental Sciences; Chugai Pharmaceutical Co. Ltd., Tokyo; Department of Pediatrics, Yokohama City University School of Medicine, Kanagawa; Department of Pediatric Cardiology, Saitama Medical University International Medical Center, Saitama; Division of Rheumatology and Clinical Immunology, Jichi Medical School, Tochigi, Japan.S. Yokota, MD, PhD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Yokohama City University School of Medicine; Y. Itoh, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Nippon Medical School; T. Morio, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics and Developmental Biology, TMDU Graduate School of Medical and Dental Sciences; N. Sumitomo, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatric Cardiology, Saitama Medical University International Medical Center; K. Daimaru, BS, Chugai Pharmaceutical Co. Ltd.; S. Minota, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Division of Rheumatology and Clinical Immunology, Jichi Medical School.
authors: Naokata
authors: N
authors: Sumitomo
authors: From The Safety Evaluation Committee of Tocilizumab for JIA; Department of Pediatrics, Nippon Medical School; Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU) Graduate School of Medical and Dental Sciences; Chugai Pharmaceutical Co. Ltd., Tokyo; Department of Pediatrics, Yokohama City University School of Medicine, Kanagawa; Department of Pediatric Cardiology, Saitama Medical University International Medical Center, Saitama; Division of Rheumatology and Clinical Immunology, Jichi Medical School, Tochigi, Japan.S. Yokota, MD, PhD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Yokohama City University School of Medicine; Y. Itoh, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Nippon Medical School; T. Morio, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics and Developmental Biology, TMDU Graduate School of Medical and Dental Sciences; N. Sumitomo, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatric Cardiology, Saitama Medical University International Medical Center; K. Daimaru, BS, Chugai Pharmaceutical Co. Ltd.; S. Minota, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Division of Rheumatology and Clinical Immunology, Jichi Medical School.
authors: Kaori
authors: K
authors: Daimaru
authors: From The Safety Evaluation Committee of Tocilizumab for JIA; Department of Pediatrics, Nippon Medical School; Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU) Graduate School of Medical and Dental Sciences; Chugai Pharmaceutical Co. Ltd., Tokyo; Department of Pediatrics, Yokohama City University School of Medicine, Kanagawa; Department of Pediatric Cardiology, Saitama Medical University International Medical Center, Saitama; Division of Rheumatology and Clinical Immunology, Jichi Medical School, Tochigi, Japan.S. Yokota, MD, PhD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Yokohama City University School of Medicine; Y. Itoh, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics, Nippon Medical School; T. Morio, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatrics and Developmental Biology, TMDU Graduate School of Medical and Dental Sciences; N. Sumitomo, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Department of Pediatric Cardiology, Saitama Medical University International Medical Center; K. Daimaru, BS, Chugai Pharmaceutical Co. Ltd.; S. Minota, MD, the Safety Evaluation Committee of Tocilizumab for JIA, and the Division of Rheumatology and Clinical Immunology, Jichi Medical School.
authors: Seiji
authors: S
authors: Minota
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000150:complications* / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D055501:Macrophage Activation Syndrome / Q000150:complications*; D008297:Male; D012042:Registries; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab
keywords: INFECTION-ASSOCIATED HEMOPHAGOCYTIC SYNDROME; INTERLEUKINS; JUVENILE IDIOPATHIC ARTHRITIS; MACROPHAGE ACTIVATION SYNDROME; POSTMARKETING PRODUCT SURVEILLANCE; TOCILIZUMAB