3个月与12个月的romosozumab治疗绝经后骨质疏松症（LIDA）：一项开放标签、非劣效性、随机对照试验

摘要(中文译文)

绝经后骨质疏松症是一种高度流行的疾病，具有较高的发病率和死亡率。最近推出的骨质疏松症药物是romosozumab，这是一种单克隆抗体，具有独特的作用机制，通过刺激新骨形成和抑制再吸收，比其他药物更能增加骨矿物质密度（BMD）。然而，这种药物对骨形成的刺激作用在几个月后就会减弱。romosozumab的使用受到成本、每月临床注射的不便及其心血管风险的限制。在这项试验中，我们的目的是检验一个假设，即较短疗程的romosozumab可能与标准方案同样有效。我们对50名绝经后骨折高危妇女进行了为期12个月的前瞻性、开放标签、随机、对照、非劣效性试验。这项研究是在美国的一个学术医疗中心进行的。参与者被随机分配接受3个月的romosozumab（每月皮下注射210毫克），然后接受9个月的denosumab（每6个月皮下注射60毫克；3个月ROMO组）或12个月的rom sozumab。主要终点是全髋关节骨密度的百分比变化。非劣效性阈值设定为2%。该试验在ClinicalTrials.gov注册，NCT05010590。2022年3月2日至2023年5月2日，我们筛选了188名参与者。其中，102人（54%）没有资格参加，36人（19%）拒绝参加。我们将50名参与者随机分配到3个月的ROMO组（24名[48%]参与者）或12个月的ROM组（26名[52%]参与者）。完成至少一次基线后访视的研究参与者被纳入分析（改良意向治疗分析）。参与者的平均年龄为69.6岁（SD 4.5）。在3个月的romosozumab组中，全髋关节BMD的平均12个月变化为5.7%（SD 3.3），在12个月的roosozumak组中为6.0%（3.2），符合预先设定的非劣效性阈值。不良事件（背痛、咳嗽、疲劳、头痛、关节疼痛、肌肉痉挛、肌肉疼痛、心悸、感觉异常、注射部位反应、鼻漏、皮疹和肿胀）在两组之间保持平衡。在骨折风险较高的绝经后妇女中，3个月的romosozumab和9个月的denosumab在提高全髋关节骨密度方面并不亚于12个月的roosozumab.考虑到romosozuma的费用、注射负担和潜在的不良反应，这种简化的方法可以扩大这种独特有效疗法的可及性。美国国家关节炎、肌肉骨骼和皮肤病研究所和美国国家推进转化科学中心。

Abstract

Postmenopausal osteoporosis is a highly prevalent disease associated with substantial morbidity and mortality. The most recently introduced osteoporosis medication is romosozumab, a monoclonal antibody with a unique mechanism of action that increases bone mineral density (BMD) more than other agents by both stimulating new bone formation and inhibiting resorption. The drug's stimulation of bone formation, however, wanes after several months. The use of romosozumab is limited by cost, the inconvenience of monthly clinic-administered injections, and its cardiovascular risk profile. In this trial, we aimed to test the hypothesis that a shorter course of romosozumab might be equally effective as the standard regimen. We did a 12-month, prospective, open-label, randomised, controlled, non-inferiority trial of 50 postmenopausal women at high risk of fracture. The study was done at a single academic medical centre in the USA. Participants were randomly assigned to receive 3 months of romosozumab (210 mg by subcutaneous injection, monthly) followed by 9 months of denosumab (60 mg by subcutaneous injection, every 6 months; 3-month ROMO group) or 12 months of romosozumab (12-month ROMO group). The primary endpoint was the percentage change in total hip BMD. The non-inferiority threshold was set at 2%. The trial was registered at ClinicalTrials.gov, NCT05010590. Between March 2, 2022, and May 2, 2023, we screened 188 participants. Of those, 102 (54%) were ineligible and 36 (19%) declined to participate. We randomly assigned 50 participants to either the 3-month ROMO group (24 [48%] participants) or the 12-month ROMO group (26 [52%] participants). Study participants completing at least one post-baseline visit were included in the analysis (modified intention-to-treat analysis). The mean age of participants was 69·6 years (SD 4·5). The mean 12-month change in total hip BMD was 5·7% (SD 3·3) in the 3-month romosozumab group and 6·0% (3·2) in the 12-month romosozumab group, meeting the prespecified non-inferiority threshold. Adverse events (back pain, cough, fatigue, headache, joint pain, muscle cramps, muscle pain, palpitations, paraesthesia, reaction at injection site, rhinorrhoea, skin rash, and swelling) were balanced between groups. In postmenopausal women at high risk of fracture, 3 months of romosozumab followed by 9 months of denosumab was non-inferior to 12 months of romosozumab in increasing total hip BMD. Given the expense, injection burden, and potential adverse effects of romosozumab, this abbreviated approach could broaden access to this uniquely effective therapy. US National Institute of Arthritis and Musculoskeletal and Skin Diseases and US National Center for Advancing Translational Science.

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