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
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
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地诺单抗对日本类风湿性关节炎患者的影响：类风湿性关节炎患者中 AMG 162（地诺单抗）对甲氨蝶呤的剂量反应研究，以验证对骨侵蚀的抑制作用 (DRIVE)——一项为期 12 个月、多中心、随机、双研究盲法、安慰剂对照、II 期
DOI：
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发表时间：
2015
影响因子：
27.4
通讯作者：
D. M. van der Heijde
中科院分区：
文献类型：
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作者：
T. Takeuchi;Yoshiya Tanaka;N. Ishiguro;H. Yamanaka;T. Yoneda;Takeshi Ohira;N. Okubo;H. Genant;D. M. van der Heijde
目的评价地舒单抗（一种抗核因子κ受体激活剂B（RANK）配体（RANKL）的全人源单克隆抗体）治疗日本类风湿关节炎（RA）患者的3种不同方案的疗效和安全性。方法在这项多中心、随机、安慰剂对照的II期研究中，350例6个月至<5岁的日本RA患者按糖皮质激素使用和类风湿因子状态分层，随机分配至皮下注射安慰剂或地舒单抗60 mg，每6个月（Q6 M）、每3个月（Q3 M）或每2个月（Q2 M）。 所有患者基本上继续甲氨蝶呤治疗，并在整个研究期间补充钙和维生素D。主要终点是改良Sharp糜烂评分从基线至12个月的变化。 结果与安慰剂相比，地舒单抗在12个月时明显抑制了骨侵蚀的进展，安慰剂、Q6 M、Q3 M和Q2 M组12个月时改良Sharp侵蚀评分较基线的平均变化分别为0.99、0.27（与安慰剂相比，p=0.0082）、0.14（p=0.0036）和0.09（p<0.0001）。 次要终点分析显示，与安慰剂相比，地舒单抗还可显著抑制改良Sharp总分的增加，没有明显证据表明地舒单抗对关节间隙狭窄有影响。如既往研究所示，地舒单抗可增加骨密度。Denosumab和安慰剂的安全性特征未观察到明显差异。结论地舒单抗联合甲氨蝶呤治疗有关节破坏危险因素的类风湿关节炎有可能成为一种新的治疗选择。试验注册号JapicCTI-101263。
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.