title: Longterm safety and effectiveness of the anti-interleukin 6 receptor monoclonal antibody tocilizumab in patients with systemic juvenile idiopathic arthritis in Japan.
abstract: OBJECTIVE
  To assess the longterm safety and effectiveness of tocilizumab (TCZ) in systemic-onset juvenile idiopathic arthritis (sJIA).
  
  
  METHODS
  The longterm extension phase of 2 pivotal studies (phase II with 11 patients and phase III with 56 patients) in patients with active sJIA was analyzed. Patients received open-label TCZ (8 mg/kg, every 2 weeks) without concomitant use of disease-modifying antirheumatic drugs.
  
  
  RESULTS
  In total, 67 patients were enrolled. All patients received corticosteroid at baseline. Median duration of exposure to TCZ was 3.4 years. Nine patients withdrew from the study [4 because of adverse events (AE), 4 because of the development of anti-TCZ antibodies, and 1 because of inadequate response]. Rates of AE and serious AE were 803.7/100 patient-years (PY) and 34.7/100 PY, respectively. The most common serious AE were infections (13.2/100 PY). No cases of malignancy or death were reported. Two serious infusion reactions were reported in patients testing negative for anti-TCZ antibodies. One definite macrophage activation syndrome (MAS) case and 1 potential MAS case were identified. American College of Rheumatology (ACR) response rates attained early in the TCZ treatment period were maintained throughout the study: at Week 168, JIA ACR 30, 50, 70, 90, and 100 response rates were 80.3%, 80.3%, 75.4%, 60.7%, and 18.0%, respectively. In total, 22 of 67 patients (32.8%) completely discontinued corticosteroids without flare.
  
  
  CONCLUSIONS
  TCZ has demonstrated durability of effectiveness in the longterm treatment of children with sJIA and has shown good tolerability and a low discontinuation rate associated with AE, development of anti-TCZ antibodies, or inadequate response. (ClinicalTrials.gov NCT00144599 and NCT00144612). (First Release March 15 2014; J Rheumatol 2014;41:759-67; doi:10.3899/jrheum.130690).
authors.affiliation: From the Department of Pediatrics, Yokohama City University School of Medicine, and Department of Pediatrics, Yokohama City University Medical Center; Yokohama; School of Health Science, Faculty of Medicine, Kagoshima University, Kagoshima; Aichi Children's Health and Medical Center, Aichi; Miyagi Children's Hospital, Miyagi; Department of Pediatrics, Osaka Medical College, Osaka; Kobe Children's Hospital, Kobe; Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba; Department of Molecular Regulation for Intractable Diseases, Institute of Medical Science, Tokyo Medical University, Osaka; Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Yokota
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Imagawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mori
authors.forename: Takako
authors.initials: T
authors.lastname: Miyamae
authors.forename: Syuji
authors.initials: S
authors.lastname: Takei
authors.forename: Naomi
authors.initials: N
authors.lastname: Iwata
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Umebayashi
authors.forename: Takuji
authors.initials: T
authors.lastname: Murata
authors.forename: Mari
authors.initials: M
authors.lastname: Miyoshi
authors.forename: Minako
authors.initials: M
authors.lastname: Tomiita
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nishimoto
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D008297:Male; D020714:Maximum Tolerated Dose; D061214:Patient Safety; D019947:Receptors, Interleukin-6 / Q000276:immunology* / Q000627:therapeutic use*; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D019947:Receptors, Interleukin-6; C502936:tocilizumab
keywords: DISEASE-MODIFYING ANTIRHEUMATIC DRUG; INTERLEUKIN 6 ANTAGONISTS AND INHIBITORS; JUVENILE IDIOPATHIC ARTHRITIS; TOCILIZUMAB