Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study

nipocalimab在成人全身性重症肌无力 (Vivacity-MG3) 中的安全性和有效性: 一项3期，随机，双盲，安慰剂对照研究

Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study. Results from the completed double-blind phase of Vivacity-MG3 support the role of nipocalimab, added to standard-of-care therapies, as a safe treatment for sustained disease control over 6 months for a broad population of patients with generalised myasthenia gravis who are antibody-positive. The ongoing open-label extension phase should provide longer term sustained safety and efficacy data with nipocalimab.

鉴于常规药物的繁重的副作用和长的疗效潜伏期，仍然需要安全的全身性重症肌无力治疗，并提供持续的长期疾病控制。Nipocalimab是一种新生儿Fc受体阻滞剂，与总IgG和抗乙酰胆碱受体 (AChR) 抗体的剂量依赖性减少以及重症肌无力患者日常生活活动 (mg-adl) 量表在临床上有意义的改善有关2期研究中的重症肌无力。我们的目的是在一项3期研究中评估nipocalimab的安全性和有效性。完成的双盲Vivacity-MG3阶段的结果支持了nipocalimab的作用，该作用已添加到护理标准疗法中，可作为广泛的抗体阳性的全身性重症肌无力患者持续6个月的疾病控制的安全疗法。正在进行的开放标签扩展阶段应提供nipocalimab的长期持续安全性和有效性数据。

REF: Antozzi C, Vu T, Ramchandren S, et al. Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2025;24(2):105-116. doi:10.1016/S1474-4422(24)00498-8 PMID: 39862879

Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial

satralizumab在全身性重症肌无力患者中的安全性和有效性 (LUMINESCE): 一项随机，双盲，多中心，安慰剂对照的3期试验

Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis. Satralizumab was well tolerated and resulted in small improvements in patient-reported and clinician-reported outcomes compared with placebo at week 24 in patients with AChR-IgG-positive generalised myasthenia gravis. Further research analysing the immunological underpinnings of the observed clinical response to IL-6 signalling inhibition in patients with generalised myasthenia gravis and exploring the role of IL-6 in autoantibody-mediated diseases is warranted.

临床前研究的证据表明，IL-6信号传导具有调节全身性重症肌无力患者自身抗体效应机制上游的免疫病理机制的潜力。我们旨在评估satralizumab (一种靶向IL-6受体的人源化单克隆抗体) 在全身性重症肌无力患者中的安全性和有效性。在24周时，与安慰剂相比，Satralizumab具有良好的耐受性，并导致患者报告和临床医生报告的结局有小幅改善。有必要进行进一步的研究，以分析在全身性重症肌无力患者中观察到的对IL-6信号抑制的临床反应的免疫学基础，并探索IL-6在自身抗体介导的疾病中的作用。

REF: Habib AA, Zhao C, Aban I, et al. Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2025;24(2):117-127. doi:10.1016/S1474-4422(24)00514-3 PMID: 39862880

Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial

鼻内催产素治疗额颞叶痴呆患者的冷漠 (FOXY): 一项多中心、随机、双盲、安慰剂对照、适应性、交叉、2a/2b期优越性试验

No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia. Intranasal oxytocin given every third day was well tolerated and was associated with a small reduction in apathy in patients with frontotemporal dementia. Future trials might investigate intermittent dosing of more potent formulations than in this study, to establish whether larger effects are possible.

额颞痴呆患者的冷漠没有治疗方法。以前，在一项随机双盲，安慰剂对照，剂量发现研究中，鼻内催产素给药在额颞痴呆患者中改善了神经精神病学量表的冷漠评级超过1周，在一项随机，双盲，安慰剂对照，交叉研究中，单剂量72 IU催产素可增加边缘脑区域的血氧水平依赖性信号。我们的目的是确定延长催产素治疗时间是否能改善额颞叶痴呆患者的冷漠。鼻内催产素每三天给药一次，耐受性良好，并且与额颞叶痴呆患者的淡漠减少有关。未来的试验可能会研究比本研究更有效的制剂的间歇给药，以确定是否可能产生更大的效果。

REF: Coleman KKL, Berry S, Cummings J, et al. Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial. Lancet Neurol. 2025;24(2):128-139. doi:10.1016/S1474-4422(24)00456-3 PMID: 39862881

Apixaban versus aspirin for stroke prevention in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack: subgroup analysis of the ARTESiA randomised controlled trial

阿哌沙班与阿司匹林在亚临床心房颤动和卒中或短暂性脑缺血发作史患者中的卒中预防作用: ARTESiA随机对照试验的亚组分析

People with subclinical atrial fibrillation are at increased risk of stroke, albeit to a lesser extent than those with clinical atrial fibrillation, leading to an ongoing debate regarding the benefit of anticoagulation in these individuals. In the ARTESiA trial, the direct-acting oral anticoagulant apixaban reduced stroke or systemic embolism compared with aspirin in people with subclinical atrial fibrillation, but the risk of major bleeding was increased with apixaban. In a prespecified subgroup analysis of ARTESiA, we tested the hypothesis that people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack, who are known to have an increased risk of recurrent stroke, would show a greater benefit from oral anticoagulation for secondary stroke prevention compared with those without a history of stroke or transient ischaemic attack. Treatment with the direct-acting oral anticoagulant apixaban in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack led to a 7% absolute risk reduction in stroke or systemic embolism over 3·5 years, compared with a 1% absolute risk reduction for individuals without a previous history of stroke or transient ischaemic attack. The corresponding absolute increase in major bleeding was 3% and 1%, respectively. Apixaban could be considered for secondary stroke prevention in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack.

亚临床心房颤动患者的卒中风险增加，尽管程度低于临床心房颤动患者，这导致了关于这些患者抗凝治疗益处的持续争论。在ARTESiA试验中，与阿司匹林相比，直接作用口服抗凝药阿哌沙班在亚临床房颤患者中减少了卒中或全身性栓塞，但阿哌沙班增加了大出血的风险。在一项预设的ARTESiA亚组分析中，我们检验了以下假设: 患有亚临床心房颤动且有卒中或短暂性脑缺血发作史的人，这些人的复发性卒中风险增加，与没有卒中或短暂性脑缺血发作史的患者相比，口服抗凝药物用于二级卒中预防的获益更大。在亚临床心房颤动和卒中或短暂性脑缺血发作史患者中，使用直接作用口服抗凝剂阿哌沙班治疗可在3·5年内使卒中或全身性栓塞的绝对风险降低7%，与以前没有卒中或短暂性脑缺血发作史的个体相比，绝对风险降低了1%。相应的大出血绝对增加量分别为3% 和1%。阿哌沙班可考虑用于亚临床房颤和卒中或短暂性脑缺血发作史患者的二级卒中预防。

REF: Shoamanesh A, Field TS, Coutts SB, et al. Apixaban versus aspirin for stroke prevention in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack: subgroup analysis of the ARTESiA randomised controlled trial. Lancet Neurol. 2025;24(2):140-151. doi:10.1016/S1474-4422(24)00475-7 PMID: 39862882

Unique considerations in the assessment and management of traumatic brain injury in older adults

老年人创伤性脑损伤的评估和管理中的独特考虑

The age-specific incidence of traumatic brain injury in older adults is rising in high-income countries, mainly due to an increase in the incidence of falls. The severity of traumatic brain injury in older adults can be underestimated because of a delay in the development of mass effect and symptoms of intracranial haemorrhage. Management and rehabilitation in older adults must consider comorbidities and frailty, the treatment of pre-existing disorders, the reduced potential for recovery, the likelihood of cognitive decline, and the avoidance of future falls. Older age is associated with worse outcomes after traumatic brain injury, but premorbid health is an important predictor and good outcomes are achievable. Although prognostication is uncertain, unsubstantiated nihilism (eg, early withdrawal decisions from the assumption that old age necessarily leads to poor outcomes) should be avoided. The absence of management recommendations for older adults highlights the need for stronger evidence to enhance prognostication. In the meantime, decision making should be multidisciplinary, transparent, personalised, and inclusive of patients and relatives.

在高收入国家，老年人创伤性脑损伤的年龄特异性发病率正在上升，这主要是由于跌倒发生率的增加。由于质量效应和颅内出血症状的发展延迟，老年人创伤性脑损伤的严重程度可能被低估。老年人的管理和康复必须考虑合并症和虚弱，先前存在的疾病的治疗，恢复的可能性降低，认知能力下降的可能性以及避免将来跌倒。年龄越大，创伤性脑损伤后的预后越差，但病前健康是一个重要的预测指标，良好的预后是可以实现的。尽管预后不确定，但应避免未经证实的虚无主义 (例如，从老年必然导致不良结果的假设出发的早期退出决定)。缺乏针对老年人的管理建议，这凸显了需要更有力的证据来增强预后。同时，决策应该是多学科的，透明的，个性化的，并包括患者和亲属。

REF: Depreitere B, Becker C, Ganau M, et al. Unique considerations in the assessment and management of traumatic brain injury in older adults. Lancet Neurol. 2025;24(2):152-165. doi:10.1016/S1474-4422(24)00454-X PMID: 39862883