From the University of Alabama, Birmingham (K.G.S.); Amgen, Thousand Oaks, CA (J.P., J.M., M.F., A.G.); University of Florence, Florence, Italy (M.L.B.); McGill University, Montreal (A.C.K.); University of Gothenburg and Sahlgrenska University Hospital, Mölndal, Sweden (M.L.); Centre Hospitalier Universitaire de Saint-Étienne, Saint-Étienne, France (T.T.); and UCB Pharma, Brussels (P.D.M.).
N Engl J Med. 2017 Oct 12;377(15):1417-1427. doi: 10.1056/NEJMoa1708322. Epub 2017 Sep 11.
Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption.
We enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups. The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture (nonvertebral and symptomatic vertebral fracture) at the time of the primary analysis (after clinical fractures had been confirmed in ≥330 patients). Secondary end points included the incidences of nonvertebral and hip fracture at the time of the primary analysis. Serious cardiovascular adverse events, osteonecrosis of the jaw, and atypical femoral fractures were adjudicated.
Over a period of 24 months, a 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group (6.2% [127 of 2046 patients]) than in the alendronate-to-alendronate group (11.9% [243 of 2047 patients]) (P<0.001). Clinical fractures occurred in 198 of 2046 patients (9.7%) in the romosozumab-to-alendronate group versus 266 of 2047 patients (13.0%) in the alendronate-to-alendronate group, representing a 27% lower risk with romosozumab (P<0.001). The risk of nonvertebral fractures was lower by 19% in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group (178 of 2046 patients [8.7%] vs. 217 of 2047 patients [10.6%]; P=0.04), and the risk of hip fracture was lower by 38% (41 of 2046 patients [2.0%] vs. 66 of 2047 patients [3.2%]; P=0.02). Overall adverse events and serious adverse events were balanced between the two groups. During year 1, positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate (50 of 2040 patients [2.5%] vs. 38 of 2014 patients [1.9%]). During the open-label alendronate period, adjudicated events of osteonecrosis of the jaw (1 event each in the romosozumab-to-alendronate and alendronate-to-alendronate groups) and atypical femoral fracture (2 events and 4 events, respectively) were observed.
In postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone. (Funded by Amgen and others; ARCH ClinicalTrials.gov number, NCT01631214 .).
罗莫索单抗是一种单克隆抗体，可与骨硬化素结合并抑制其活性，从而增加骨形成并减少骨吸收。
我们招募了 4093 名绝经后骨质疏松症和脆性骨折的女性患者，将其随机以 1:1 的比例分为两组，分别接受每月皮下注射罗莫索单抗（210mg）或每周口服阿仑膦酸钠（70mg），共 12 个月，随后两组均转为开放标签的阿仑膦酸钠治疗。主要终点为 24 个月时新发椎体骨折的累积发生率和主要分析时（在≥330 例患者中确认临床骨折后）的临床骨折（非椎体和症状性椎体骨折）的累积发生率。次要终点包括主要分析时非椎体和髋部骨折的发生率。严重心血管不良事件、颌骨坏死和非典型股骨骨折通过裁决得出。
在 24 个月的治疗期间，与阿仑膦酸钠单药组（11.9%[243/2047 例]）相比，罗莫索单抗-阿仑膦酸钠组新发椎体骨折的风险降低了 48%（6.2%[127/2046 例]）（P<0.001）。罗莫索单抗-阿仑膦酸钠组有 198 例（9.7%）患者发生临床骨折，阿仑膦酸钠-阿仑膦酸钠组有 266 例（13.0%）患者发生临床骨折，罗莫索单抗降低骨折风险 27%（P<0.001）。罗莫索单抗-阿仑膦酸钠组非椎体骨折的风险降低了 19%（178/2046 例[8.7%]），阿仑膦酸钠-阿仑膦酸钠组为 217/2047 例[10.6%]；P=0.04），髋部骨折的风险降低了 38%（41/2046 例[2.0%]），阿仑膦酸钠-阿仑膦酸钠组为 66/2047 例[3.2%]；P=0.02）。两组之间的总体不良事件和严重不良事件是平衡的。在第一年，罗莫索单抗的严重心血管不良事件发生率高于阿仑膦酸钠（罗莫索单抗组 2040 例中有 50 例[2.5%]，阿仑膦酸钠组 2014 例中有 38 例[1.9%]）。在开放标签的阿仑膦酸钠治疗期间，颌骨坏死（罗莫索单抗-阿仑膦酸钠组和阿仑膦酸钠-阿仑膦酸钠组各 1 例）和非典型股骨骨折（罗莫索单抗-阿仑膦酸钠组 2 例，阿仑膦酸钠-阿仑膦酸钠组 4 例）的裁决事件。
在有高骨折风险的绝经后骨质疏松症女性中，罗莫索单抗治疗 12 个月后再用阿仑膦酸钠治疗，与单用阿仑膦酸钠相比，骨折风险显著降低。（由 Amgen 等资助；ARCH 临床试验.gov 编号，NCT01631214）。
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