title: Longterm Safety of Tocilizumab: Results from 3 Years of Followup Postmarketing Surveillance of 5573 Patients with Rheumatoid Arthritis in Japan.
abstract: OBJECTIVE
  To evaluate the longterm safety of tocilizumab (TCZ) for the treatment of rheumatoid arthritis (RA) in a real-world clinical setting in Japan.
  
  
  METHODS
  In this longterm extension of a single-arm, observational postmarketing surveillance study, a total of 5573 patients who initiated intravenous TCZ between April 2008 and July 2009 were observed for 3 years, regardless of its continuation, for incidence of fatal events, serious infections, malignancy, gastrointestinal perforations, and serious cardiac dysfunction.
  
  
  RESULTS
  Of the 5573 patients who were enrolled, 4527 patients (81.23%) completed 3 years of followup. There were no increases in the proportions of patients with fatal events, serious infection, malignancy, GI perforation, or serious cardiac dysfunction over 3 years. The all-cause mortality rate during followup was 2.58% (0.95/100 patient-yrs), and the standardized mortality ratio was 1.27 (95% CI, 1.08 to 1.50). Patients who were older with longer disease duration and respiratory comorbidities were more likely to discontinue TCZ treatment following serious infection during the first year. Among patients who completed 3 years of TCZ treatment, serious infection developed at a constant rate during the 3-year treatment period. The proportion of malignancy during followup was 2.24% (0.83/100 patient-yrs), and the standardized incidence ratio was 0.79 (95% CI, 0.66 to 0.95).
  
  
  CONCLUSIONS
  The safety profile of TCZ was consistent over time regarding mortality, serious infections, malignancy, gastrointestinal perforation, and serious cardiac dysfunction. These data confirm the longterm safety of TCZ use in patients with RA in a real-world clinical setting.
authors.affiliation: From the Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; Department of Respiratory Medicine, Fukujuji Hospital; Heart Rhythm Center, Tokyo Medical and Dental University; Department of Rheumatology, Tokyo Metropolitan Police Hospital, Tokyo; Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine, Toyama; Chugai Pharmaceutical Co. Ltd.; Department of Internal Medicine, Kitatama Hospital, Tokyo, Japan.K. Yamamoto, MD, PhD, Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; H. Goto, MD, PhD, Department of Respiratory Medicine, Fukujuji Hospital; K. Hirao, MD, PhD, Heart Rhythm Center, Tokyo Medical and Dental University; A. Nakajima, MD, PhD, Department of Rheumatology, Tokyo Metropolitan Police Hospital; H. Origasa, PhD, Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine; K. Tanaka, MSc; M. Tomobe, BPharm, Chugai Pharmaceutical Co. Ltd.; K. Totsuka, MD, PhD, Department of Internal Medicine, Kitatama Hospital. yamamoto-tky@umin.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: From the Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; Department of Respiratory Medicine, Fukujuji Hospital; Heart Rhythm Center, Tokyo Medical and Dental University; Department of Rheumatology, Tokyo Metropolitan Police Hospital, Tokyo; Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine, Toyama; Chugai Pharmaceutical Co. Ltd.; Department of Internal Medicine, Kitatama Hospital, Tokyo, Japan.K. Yamamoto, MD, PhD, Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; H. Goto, MD, PhD, Department of Respiratory Medicine, Fukujuji Hospital; K. Hirao, MD, PhD, Heart Rhythm Center, Tokyo Medical and Dental University; A. Nakajima, MD, PhD, Department of Rheumatology, Tokyo Metropolitan Police Hospital; H. Origasa, PhD, Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine; K. Tanaka, MSc; M. Tomobe, BPharm, Chugai Pharmaceutical Co. Ltd.; K. Totsuka, MD, PhD, Department of Internal Medicine, Kitatama Hospital.
authors.forename: Hajime
authors.initials: H
authors.lastname: Goto
authors.affiliation: From the Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; Department of Respiratory Medicine, Fukujuji Hospital; Heart Rhythm Center, Tokyo Medical and Dental University; Department of Rheumatology, Tokyo Metropolitan Police Hospital, Tokyo; Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine, Toyama; Chugai Pharmaceutical Co. Ltd.; Department of Internal Medicine, Kitatama Hospital, Tokyo, Japan.K. Yamamoto, MD, PhD, Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; H. Goto, MD, PhD, Department of Respiratory Medicine, Fukujuji Hospital; K. Hirao, MD, PhD, Heart Rhythm Center, Tokyo Medical and Dental University; A. Nakajima, MD, PhD, Department of Rheumatology, Tokyo Metropolitan Police Hospital; H. Origasa, PhD, Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine; K. Tanaka, MSc; M. Tomobe, BPharm, Chugai Pharmaceutical Co. Ltd.; K. Totsuka, MD, PhD, Department of Internal Medicine, Kitatama Hospital.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hirao
authors.affiliation: From the Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; Department of Respiratory Medicine, Fukujuji Hospital; Heart Rhythm Center, Tokyo Medical and Dental University; Department of Rheumatology, Tokyo Metropolitan Police Hospital, Tokyo; Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine, Toyama; Chugai Pharmaceutical Co. Ltd.; Department of Internal Medicine, Kitatama Hospital, Tokyo, Japan.K. Yamamoto, MD, PhD, Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; H. Goto, MD, PhD, Department of Respiratory Medicine, Fukujuji Hospital; K. Hirao, MD, PhD, Heart Rhythm Center, Tokyo Medical and Dental University; A. Nakajima, MD, PhD, Department of Rheumatology, Tokyo Metropolitan Police Hospital; H. Origasa, PhD, Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine; K. Tanaka, MSc; M. Tomobe, BPharm, Chugai Pharmaceutical Co. Ltd.; K. Totsuka, MD, PhD, Department of Internal Medicine, Kitatama Hospital.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakajima
authors.affiliation: From the Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; Department of Respiratory Medicine, Fukujuji Hospital; Heart Rhythm Center, Tokyo Medical and Dental University; Department of Rheumatology, Tokyo Metropolitan Police Hospital, Tokyo; Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine, Toyama; Chugai Pharmaceutical Co. Ltd.; Department of Internal Medicine, Kitatama Hospital, Tokyo, Japan.K. Yamamoto, MD, PhD, Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; H. Goto, MD, PhD, Department of Respiratory Medicine, Fukujuji Hospital; K. Hirao, MD, PhD, Heart Rhythm Center, Tokyo Medical and Dental University; A. Nakajima, MD, PhD, Department of Rheumatology, Tokyo Metropolitan Police Hospital; H. Origasa, PhD, Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine; K. Tanaka, MSc; M. Tomobe, BPharm, Chugai Pharmaceutical Co. Ltd.; K. Totsuka, MD, PhD, Department of Internal Medicine, Kitatama Hospital.
authors.forename: Hideki
authors.initials: H
authors.lastname: Origasa
authors.affiliation: From the Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; Department of Respiratory Medicine, Fukujuji Hospital; Heart Rhythm Center, Tokyo Medical and Dental University; Department of Rheumatology, Tokyo Metropolitan Police Hospital, Tokyo; Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine, Toyama; Chugai Pharmaceutical Co. Ltd.; Department of Internal Medicine, Kitatama Hospital, Tokyo, Japan.K. Yamamoto, MD, PhD, Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; H. Goto, MD, PhD, Department of Respiratory Medicine, Fukujuji Hospital; K. Hirao, MD, PhD, Heart Rhythm Center, Tokyo Medical and Dental University; A. Nakajima, MD, PhD, Department of Rheumatology, Tokyo Metropolitan Police Hospital; H. Origasa, PhD, Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine; K. Tanaka, MSc; M. Tomobe, BPharm, Chugai Pharmaceutical Co. Ltd.; K. Totsuka, MD, PhD, Department of Internal Medicine, Kitatama Hospital.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: From the Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; Department of Respiratory Medicine, Fukujuji Hospital; Heart Rhythm Center, Tokyo Medical and Dental University; Department of Rheumatology, Tokyo Metropolitan Police Hospital, Tokyo; Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine, Toyama; Chugai Pharmaceutical Co. Ltd.; Department of Internal Medicine, Kitatama Hospital, Tokyo, Japan.K. Yamamoto, MD, PhD, Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; H. Goto, MD, PhD, Department of Respiratory Medicine, Fukujuji Hospital; K. Hirao, MD, PhD, Heart Rhythm Center, Tokyo Medical and Dental University; A. Nakajima, MD, PhD, Department of Rheumatology, Tokyo Metropolitan Police Hospital; H. Origasa, PhD, Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine; K. Tanaka, MSc; M. Tomobe, BPharm, Chugai Pharmaceutical Co. Ltd.; K. Totsuka, MD, PhD, Department of Internal Medicine, Kitatama Hospital.
authors.forename: Minako
authors.initials: M
authors.lastname: Tomobe
authors.affiliation: From the Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; Department of Respiratory Medicine, Fukujuji Hospital; Heart Rhythm Center, Tokyo Medical and Dental University; Department of Rheumatology, Tokyo Metropolitan Police Hospital, Tokyo; Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine, Toyama; Chugai Pharmaceutical Co. Ltd.; Department of Internal Medicine, Kitatama Hospital, Tokyo, Japan.K. Yamamoto, MD, PhD, Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo; H. Goto, MD, PhD, Department of Respiratory Medicine, Fukujuji Hospital; K. Hirao, MD, PhD, Heart Rhythm Center, Tokyo Medical and Dental University; A. Nakajima, MD, PhD, Department of Rheumatology, Tokyo Metropolitan Police Hospital; H. Origasa, PhD, Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine; K. Tanaka, MSc; M. Tomobe, BPharm, Chugai Pharmaceutical Co. Ltd.; K. Totsuka, MD, PhD, Department of Internal Medicine, Kitatama Hospital.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Totsuka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab
keywords: INTERLEUKIN 6; POSTMARKETING PRODUCT SURVEILLANCE; RHEUMATOID ARTHRITIS; TOCILIZUMAB