title: Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with rheumatoid arthritis in Japan.
abstract: OBJECTIVE
  An all-patient postmarketing surveillance program was conducted to evaluate the safety and effectiveness of tocilizumab (TCZ) for rheumatoid arthritis (RA) in the real-world clinical setting in Japan.
  
  
  METHODS
  Patients received 8 mg/kg TCZ every 4 weeks and were observed for 28 weeks. Data were collected on patient characteristics, and drug safety and effectiveness.
  
  
  RESULTS
  A total of 7901 patients were enrolled. Percentages of total and serious adverse events (AE) were 43.9% and 9.6%, respectively. The most common serious AE were infections (3.8%). Logistic regression analysis identified the following risk factors for the development of serious infection: age ≥ 65 years, disease duration ≥ 10 years, previous or concurrent respiratory disease, and concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent). The incidence rate of serious infections in patients with ≥ 3 risk factors was 11.2%, compared with 1.2% for patients without risk factors. The Week 28 rates of 28-joint Disease Activity Score-erythrocyte sedimentation rate remission, Boolean remission, and European League Against Rheumatism (EULAR) Good Response were 47.6%, 15.1%, and 59.4%, respectively. Contributing factors for effectiveness were body weight ≥ 40 kg, less advanced RA, no previous biologics, no concomitant corticosteroids or nonsteroidal antiinflammatory drugs, and low disease activity at baseline. From the benefit-risk balance analysis, patients with a high probability of remission and a low probability of developing serious infection were most likely to have less advanced RA and to have not received biologics previously.
  
  
  CONCLUSIONS
  These data confirm the safety and effectiveness of TCZ in patients with RA in the real-world clinical setting in Japan and identify factors that contribute to the successful use of TCZ for RA.
authors.affiliation: From the Sapporo Medical Center NTT EC, Sapporo; Department of Pharmacovigilance, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo; Department of Allergy and Rheumatic Disease, Japanese Red Cross Medical Center, Tokyo; Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Aichi; Nihon University, Tokyo; Division of Rheumatology/Clinical Immunology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo; School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima; The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu; Pharmacovigilance Department, Chugai Pharmaceutical Co. Ltd., Tokyo; Tokyo Women's Medical University, Tokyo; Committee on Postmarketing Surveillance of the Japan College of Rheumatology, Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Harigai
authors.forename: Shigeko
authors.initials: S
authors.lastname: Inokuma
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.forename: Junnosuke
authors.initials: J
authors.lastname: Ryu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Syuji
authors.initials: S
authors.lastname: Takei
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sano
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yaguramaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
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; D011358:Product Surveillance, Postmarketing; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab
keywords: BENEFIT RISK ASSESSMENT; BIOLOGICAL PRODUCTS; INTERLEUKINS; POSTMARKETING; RHEUMATOID ARTHRITIS; RISK FACTORS