本文由小咖机器人翻译整理

期刊来源：Lancet

原文链接：https://doi.org/10.1016/S0140-6736(23)02358-9

摘要内容如下：

背景

CD55缺乏伴补体过度激活、血管病性血栓形成和蛋白丢失性肠病（CHAPLE）是一种极其罕见的遗传性疾病，其特征是由补体系统过度激活引起的肠淋巴损伤、淋巴管扩张症和蛋白丢失性肠病。我们评估了Pozelimab（一种阻断补体成分5的抗体）的有效性和安全性。

方法

这项开放标签、单组、历史对照、多中心的2期和3期研究评估了10名Chaple病患者。本研究在泰国、Türkiye和美国的三家医院进行。1岁或1岁以上临床诊断为Chaple病的患者，通过基因分析鉴定并通过流式细胞术或外周血细胞CD55的Western印迹证实的CD55功能缺失变异符合本研究的条件。患者接受单次静脉负荷剂量的泊泽利单抗（30 mg/kg体重），随后在治疗期间根据体重每周皮下注射一次，浓度为200 mg/mL，单次注射（<40 kg体重）或两次注射（≥40 kg体重）。主要终点是在第24周时，与基线相比，血清白蛋白正常化且活跃临床结果改善且非活跃临床结果（有问题的腹痛频率、排便频率、面部水肿严重程度和外周水肿严重程度）未恶化的患者比例，在全分析数据集中进行评估。该研究已在ClinicalTrials.gov（NCT04209634）注册，目前正在进行，但尚未招募。

调查结果

在2020年1月27日至2021年5月12日期间招募了11名患者，其中10名患者被纳入研究并纳入分析人群。疗效数据对应于所有完成第48周评估并接受至少52周治疗的患者，安全性数据包括额外90天的随访，并对应于所有接受至少72周治疗的患者。患者主要是儿童（中位年龄为8.5岁），来自蒂尔基耶、叙利亚、泰国和玻利维亚。患者基线时的年龄别体重和年龄别身高明显较低，基线时的平均白蛋白为2.2 G/DL，显著低于当地实验室参考范围。在接受Pozelimab治疗后，所有10名患者的血清白蛋白均恢复正常并有所改善，临床结果没有恶化。总补体活性被完全抑制。9例患者发生不良事件；两名患者出现严重事件，一名患者出现被认为与泊泽利单有关的不良事件。

解释

Pozelimab抑制补体过度激活并解决Chaple病的临床和实验室表现。Pozelimab是目前唯一批准用于治疗这种危及生命的罕见疾病的药物。在排除了已知病因的蛋白丢失性肠病患者中，应考虑检测CD55缺陷。Chaple病的诊断应导致早期考虑使用Pozelimab治疗。

英文原文如下：

Abstracts

BACKGROUND  CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) is an ultra-rare genetic disorder characterised by intestinal lymphatic damage, lymphangiectasia, and protein-losing enteropathy caused by overactivation of the complement system. We assessed the efficacy and safety of pozelimab, an antibody blocking complement component 5.

METHODS  This open-label, single-arm, historically controlled, multicentre phase 2 and 3 study evaluated ten patients with CHAPLE disease. This study was conducted at three hospitals in Thailand, Türkiye, and the USA. Patients aged 1 year or older with a clinical diagnosis of CHAPLE disease and a CD55 loss-of-function variant identified by genetic analysis and confirmed by flow cytometry or western blot of CD55 from peripheral blood cells were eligible for this study. Patients received a single intravenous loading dose of pozelimab 30 mg per kg of bodyweight, followed by a once-per-week subcutaneous dose over the treatment period based on bodyweight at a concentration of 200 mg/mL as either a single injection (<40 kg bodyweight) or two injections (≥40 kg bodyweight). The primary endpoint was proportion of patients with serum albumin normalisation with an improvement in active clinical outcomes and no worsening in inactive clinical outcomes (frequency of problematic abdominal pain, bowel movement frequency, facial oedema severity, and peripheral oedema severity) at week 24 compared with baseline, assessed in the full analysis set. This study is registered with ClinicalTrials.gov (NCT04209634) and is active but not recruiting.

FINDINGS  11 patients were recruited between Jan 27, 2020, and May 12, 2021, ten of which were enrolled in the study and included in the analysis populations. The efficacy data corresponded to all patients completing the week 48 assessment and having at least 52 weeks of treatment exposure, and the safety data included an additional 90 days of follow-up and corresponded to all patients having at least 72 weeks of treatment. Patients were predominantly paediatric (with a median age of 8·5 years), and originated from Türkiye, Syria, Thailand, and Bolivia. Patients had markedly low weight-for-age and stature-for-age at baseline, and mean albumin at baseline was 2·2 g/dL, which was considerably less than the local laboratory reference range. After pozelimab treatment, all ten patients had serum albumin normalisation and improvement with no worsening in clinical outcomes. There was a complete inhibition of the total complement activity. Nine patients had adverse events; two were severe events, and one patient had an adverse event considered related to pozelimab.

INTERPRETATION  Pozelimab inhibits complement overactivation and resolves the clinical and laboratory manifestations of CHAPLE disease. Pozelimab is the only currently approved therapeutic drug for patients with this life-threatening, ultra-rare condition. In patients with protein-losing enteropathy where known causes have been excluded, testing for a CD55 deficiency should be contemplated. A diagnosis of CHAPLE disease should lead to early consideration of treatment with pozelimab.

-----------分割线---------

点击链接：https://www.mediecogroup.com/community/user/vip/categories/ ，成为医咖会员，获取12项专属权益。

现在购买可享受最大优惠（买一年送三个月，买两年送一年），2024年2月10日起将不再享有该优惠。