title: Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial.
abstract: OBJECTIVE
  To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA).
  
  
  METHODS
  In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months.
  
  
  RESULTS
  Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo.
  
  
  CONCLUSIONS
  Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction.
  
  
  BACKGROUND
  JapicCTI-101263.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Aichi, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoneda
authors.affiliation: Daiichi-Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ohira
authors.affiliation: Daiichi-Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Okubo
authors.affiliation: Departments of Radiology, Medicine and Orthopaedic Surgery, University of California, San Francisco, California, USA.
authors.forename: Harry K
authors.initials: HK
authors.lastname: Genant
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Désirée
authors.identifier: http://orcid.org/0000-0002-5781-158X
authors.initials: D
authors.lastname: van der Heijde
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D000069448:Denosumab / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood
chemical_list: D018501:Antirheumatic Agents; D050071:Bone Density Conservation Agents; D000069448:Denosumab; D012217:Rheumatoid Factor; D008727:Methotrexate
keywords: Bone Mineral Density; Rheumatoid Arthritis; Treatment