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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
  1. Tsutomu Takeuchi1,
  2. Yoshiya Tanaka2,
  3. Naoki Ishiguro3,
  4. Hisashi Yamanaka4,
  5. Toshiyuki Yoneda5,
  6. Takeshi Ohira6,
  7. Naoki Okubo6,
  8. Harry K Genant7,
  9. Désirée van der Heijde8
  1. 1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  2. 2First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
  3. 3Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Aichi, Japan
  4. 4Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
  5. 5Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana, USA
  6. 6Daiichi-Sankyo Co., Ltd., Tokyo, Japan
  7. 7Departments of Radiology, Medicine and Orthopaedic Surgery, University of California, San Francisco, California, USA
  8. 8Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Professor Tsutomu Takeuchi, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; tsutake{at}z5.keio.jp

Abstract

Objectives 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.

Trial registration number JapicCTI-101263.

  • Rheumatoid Arthritis
  • Bone Mineral Density
  • Treatment

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