title: Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial.
abstract: OBJECTIVE
  This phase II, dose-ranging, double-blind, placebo-controlled, randomized study (NCT01463059) evaluated efficacy and safety of olokizumab (OKZ), a humanized anti-interleukin 6 monoclonal antibody, in Asian patients with moderately-to-severely active rheumatoid arthritis (RA) who had previously failed anti-TNF therapy.
  
  
  METHODS
  Patients were randomized to one of six treatment arms: placebo or OKZ (60 mg/120 mg/240 mg every four weeks [Q4W]; or 60 mg/120 mg every two weeks [Q2W]); stratified by country and number of prior anti-TNFs. Primary efficacy variable was Week 12 change from baseline (CFB) in DAS28 CRP for 4-week cumulative dose groups of OKZ and placebo; secondary efficacy variables were Week 12 ACR20/ACR50/ACR70 response rates. Patients continued MTX treatment from baseline, without additional csDMARDs.
  
  
  RESULTS
  Of 119 randomized patients, 88.2% completed the study. Greater improvements in DAS28(CRP) mean CFB at Week 12 were observed in all OKZ 4-week cumulative dose groups (60 mg/120 mg/240 mg) versus placebo (p < 0.0001). Week 12 ACR20/ACR50 response rates were higher in all OKZ cumulative dose groups versus PBO (p < 0.05). Incidences of adverse events were similar across OKZ 4-week cumulative dose groups (76.9-84.4%) and placebo (82.8%) with no deaths.
  
  
  CONCLUSIONS
  OKZ demonstrated improvements in efficacy variables versus placebo in Asian patients with moderately-to-severely active RA who had previously failed anti-TNF therapy. The safety profile was as expected for this class of drug.
authors.affiliation: a Division of Rheumatology, Department of Internal Medicine , School of Medicine, Keio University , Tokyo, Japan .
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: b The First Department of Internal Medicine , School of Medicine, University of Occupational and Environmental Health , Kitakyushu City , Fukuoka Prefecture , Japan .
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: c Institute of Rheumatology, Tokyo Women's Medical University , Japan .
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: d Hiroshima Clinic , Hiroshima, Japan .
authors.forename: Kanzo
authors.initials: K
authors.lastname: Amano
authors.affiliation: e Center of Joint Arthroplasty and Rheumatism, Fukuoka Tokushukai Hospital , Kasuga , Fukuoka Prefecture , Japan .
authors.forename: Ryuji
authors.initials: R
authors.lastname: Nagamine
authors.affiliation: f Inha University Hospital , Incheon , Korea .
authors.forename: Won
authors.initials: W
authors.lastname: Park
authors.affiliation: g Kohnan Kakogawa Hospital , Hyogo , Japan .
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shiozawa
authors.affiliation: h Kumamoto Orthopaedic Hospital , Kumamoto, Japan .
authors.forename: Michishi
authors.initials: M
authors.lastname: Tsukano
authors.affiliation: i Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital , Taichung , Taiwan .|j Institute of Medicine, Chung Shan Medical University , Taichung , Taiwan .|k nstitute of Integrative Medicine, China Medical University , Taichung , Taiwan , and.
authors.forename: James Cheng-Chung
authors.initials: JC
authors.lastname: Wei
authors.affiliation: l UCB Pharma , Tokyo , Japan.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.affiliation: l UCB Pharma , Tokyo , Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Togo
authors.affiliation: l UCB Pharma , Tokyo , Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Mashimo
mesh_terms: D000328:Adult; D000368:Aged; 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*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C000592400:olokizumab
keywords: Anti-IL6; Anti-TNF therapy failures; DMARDs (biologic); Olokizumab; Rheumatoid arthritis