Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial.
Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial.
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DOI：
10.1016/s0140-6736(17)31613-6
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发表时间：
2017-09-30
期刊：
影响因子：
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通讯作者：
Grauer, Andreas
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文献类型：
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作者：
Langdahl, Bente L;Libanati, Cesar;Grauer, Andreas
背景：以前的双磷酸盐治疗减弱了特瑞帕泰的成骨作用。我们比较了罗莫苏珠单抗(AMG785)，一种硬化素单抗(AMG785)和特瑞帕帝对绝经后骨质疏松症患者骨密度(BMD)的影响。方法：这项随机、阶段3、开放、主动对照的研究在北美、拉丁美洲和欧洲的46个地点进行。我们招募了患有绝经后骨质疏松症的妇女(年龄从≥55岁到≤90岁)，她们在筛查前服用口服双磷酸盐至少3年，筛查前一年服用阿伦磷酸钠；全髋关节、股骨颈或腰椎的面积骨密度T评分为-2.5或更低；有骨折史。患者通过交互式语音应答系统被随机分配(1：1)接受皮下注射罗莫佐单抗(每月一次，210毫克)或皮下注射特瑞帕坦(每天一次，每次20杯)。主要终点是在整个12个月(平均6个月和12个月)，采用线性混合效应模型重复测量，代表6个月和12个月的平均治疗效果。所有接受基线测量和至少一次基线后测量的随机患者都被纳入疗效分析。这项试验在ClinicalTrials.gov注册，编号NCT01796301。FINDINGS：在2013年1月31日至2014年4月29日期间，436名患者被随机分配到romosozumab(n=218)或teriparatide(n=218)。罗莫佐单抗组206例和特派拉替组209例纳入初步疗效分析。治疗12个月后，罗莫佐单抗组髋部骨密度较治疗前平均改变2.6%(95%可信区间2·2~3·0)，药物组为-0.6%(-1~-0·2)，差异3.2%(95%可信区间2·7~3·8；P
BACKGROUND: Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy.METHODS: This randomised, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe. We enrolled women (aged ≥55 to ≤90 years) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening; an areal BMD T score of -2·5 or lower at the total hip, femoral neck, or lumbar spine; and a history of fracture. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous romosozumab (210 mg once monthly) or subcutaneous teriparatide (20 mug once daily). The primary endpoint was percentage change from baseline in areal BMD by dual-energy x-ray absorptiometry at the total hip through month 12 (mean of months 6 and 12), which used a linear mixed effects model for repeated measures and represented the mean treatment effect at months 6 and 12. All randomised patients with a baseline measurement and at least one post-baseline measurement were included in the efficacy analysis. This trial is registered with ClinicalTrials.gov, number NCT01796301.FINDINGS: Between Jan 31, 2013, and April 29, 2014, 436 patients were randomly assigned to romosozumab (n=218) or teriparatide (n=218). 206 patients in the romosozumab group and 209 in the teriparatide group were included in the primary efficacy analysis. Through 12 months, the mean percentage change from baseline in total hip areal BMD was 2·6% (95% CI 2·2 to 3·0) in the romosozumab group and -0·6% (-1·0 to -0·2) in the teriparatide group; difference 3·2% (95% CI 2·7 to 3·8; p