Cosman Felicia, Miller Paul D, Williams Gregory C, Hattersley Gary, Hu Ming-Yi, Valter Ivo, Fitzpatrick Lorraine A, Riis Bente Juel, Christiansen Claus, Bilezikian John P, Black Dennis
Department of Clinical Medicine, Columbia University, New York, NY; Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY.
Colorado Center for Bone Research, Lakewood, CO.
Mayo Clin Proc. 2017 Feb;92(2):200-210. doi: 10.1016/j.mayocp.2016.10.009.
To assess the efficacy and safety of 18 months of subcutaneous abaloparatide (ABL-SC) or placebo (PBO) followed by 6 months of alendronate (ALN) (preplanned interim analysis).
ACTIVExtend, an extension of ACTIVE, enrolled patients who completed 18 months of ABL-SC or PBO in ACTIVE to receive up to 24 additional months of open-label ALN; there was 1 month between the studies to re-consent patients.
Of 1243 eligible ACTIVE patients, 1139 (92%) were enrolled in ACTIVExtend beginning November 20, 2012. These results are from a prespecified 6-month interim analysis (cutoff date, June 2, 2015); the study is ongoing. Findings indicated percentages of patients with new morphometric vertebral fractures: PBO/ALN, 4.4% vs ABL-SC/ALN, 0.55%; relative risk reduction, 87% (relative risk, 0.13; 95% CI, 0.04-0.41; P<.001). Kaplan-Meier estimated rates of nonvertebral fractures were PBO/ALN, 5.6% vs ABL-SC/ALN, 2.7%; risk reduction, 52% (hazard ratio [HR], 0.48; 95% CI, 0.26-0.89; log-rank P=.02). There was also a 58% risk reduction of major osteoporotic fractures (HR, 0.42; 95% CI, 0.21-0.85; log-rank P=.01) and a 45% risk reduction of clinical fractures (HR, 0.55; 95% CI, 0.33-0.92; log-rank P=.02) in the ABL-SC/ALN group vs the PBO/ALN group. At 25 months, bone mineral density percentage change from ACTIVE baseline for ABL-SC/ALN vs PBO/ALN was as follows: lumbar spine, 12.8%; total hip, 5.5%; femoral neck, 4.5% vs 3.5%, 1.4%, 0.5%, respectively (group differences at all sites P<.001).
Use of ABL-SC for 18 months followed by ALN for 6 months improved bone mineral density and reduced fracture risk throughout the skeleton and may be an effective treatment option for postmenopausal women with osteoporosis.
clinicaltrials.gov Identifier: NCT01657162.
评估皮下注射阿巴洛肽（ABL-SC）18个月或安慰剂（PBO）18个月后再使用阿仑膦酸钠（ALN）6个月的疗效和安全性（预先计划的中期分析）。
ACTIVE扩展试验（ACTIVExtend）是ACTIVE试验的延伸，纳入了在ACTIVE试验中完成18个月ABL-SC或PBO治疗的患者，使其接受长达24个月的开放标签ALN治疗；两项研究之间有1个月时间让患者重新签署知情同意书。
在1243名符合条件的ACTIVE患者中，1139名（92%）于2012年11月20日开始纳入ACTIVExtend试验。这些结果来自预先设定的6个月中期分析（截止日期为2015年6月2日）；该研究仍在进行中。研究结果显示新发形态计量学椎体骨折患者的百分比：PBO/ALN组为4.4%，ABL-SC/ALN组为0.55%；相对风险降低87%（相对风险为0.13；95%置信区间为0.04 - 0.41；P <.001）。Kaplan-Meier法估计的非椎体骨折发生率：PBO/ALN组为5.6%，ABL-SC/ALN组为2.7%；风险降低52%（风险比[HR]为0.48；95%置信区间为0.26 - 0.89；对数秩检验P = 0.02）。ABL-SC/ALN组与PBO/ALN组相比，主要骨质疏松性骨折风险降低58%（HR为0.42；95%置信区间为0.21 - 0.85；对数秩检验P = 0.01），临床骨折风险降低45%（HR为0.55；95%置信区间为0.33 - 0.92；对数秩检验P = 0.02）。在25个月时，ABL-SC/ALN组与PBO/ALN组相比，相对于ACTIVE试验基线的骨矿物质密度百分比变化如下：腰椎分别为12.8%、3.5%；全髋分别为5.5%、1.4%；股骨颈分别为4.5%、0.5%（所有部位组间差异P <.001）。
先使用ABL-SC治疗18个月，再使用ALN治疗6个月，可提高骨矿物质密度，并降低全身骨折风险，可能是绝经后骨质疏松症女性的一种有效治疗选择。
clinicaltrials.gov标识符：NCT01657162
