Kazuhiko Yamamoto1, Hajime Goto2, Kenzo Hirao2, Atsuo Nakajima2, Hideki Origasa2, Kunihiko Tanaka2, Minako Tomobe2, Kyoichi Totsuka2. 1. 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. 2. 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.
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). CONCLUSION: 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.
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). CONCLUSION: 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: Peter K K Wong; Hanish Bagga; Claire Barrett; Geoff Chong; Patrick Hanrahan; Teja Kodali; Mona Marabani; H Miles Prince; John Riordan; Phillip Swarbrick; Ray White; Laurel Young Journal: Curr Rheumatol Rep Date: 2018-09-01 Impact factor: 4.592
Authors: F Iannone; G Ferraccioli; L Sinigaglia; E G Favalli; P Sarzi-Puttini; F Atzeni; R Gorla; C Bazzani; M Govoni; I Farina; E Gremese; A Carletto; A Giollo; M Galeazzi; R Foti; L Bianchino; L La Grasta; G Lapadula Journal: Clin Rheumatol Date: 2017-10-05 Impact factor: 2.980