PT - JOURNAL ARTICLE AU - Tsutomu Takeuchi AU - Yoshiya Tanaka AU - Naoki Ishiguro AU - Hisashi Yamanaka AU - Toshiyuki Yoneda AU - Takeshi Ohira AU - Naoki Okubo AU - Harry K Genant AU - Désirée van der Heijde TI - Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose–response study of AMG 162 (<em>D</em>enosumab) in patients with <em>R</em>heumato<em>I</em>d arthritis on methotrexate to <em>V</em>alidate inhibitory effect on bone <em>E</em>rosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial AID - 10.1136/annrheumdis-2015-208052 DP - 2016 Jun 01 TA - Annals of the Rheumatic Diseases PG - 983--990 VI - 75 IP - 6 4099 - http://ard.bmj.com/content/75/6/983.short 4100 - http://ard.bmj.com/content/75/6/983.full SO - Ann Rheum Dis2016 Jun 01; 75 AB - 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 &lt;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&lt;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.