用于辅助诊断非典型溶血尿毒综合征的PLASMIC评分：C5抑制剂临床试验及PINC AI™医疗数据库分析

PLASMIC score to aid diagnosis of aHUS: an analysis of C5 inhibitor clinical trials and the PINC AI™ healthcare database.

作者信息

Uriol-Rivera Miguel G, Ernst Frank R, Booth John N, Comas Àngels, Gasteyger Christoph, Tomazos Ioannis, Lum Ching, Wang Yan, Ávila Ana I

机构信息

Glomerular Diseases Unit, Son Espases University Hospital, Palma de Mallorca, Spain.

CTI Clinical Trial and Consulting Services, Inc, Covington, KY, USA.

出版信息

BMC Nephrol. 2025 May 15;26(1):241. doi: 10.1186/s12882-025-04156-6.

DOI:10.1186/s12882-025-04156-6

PMID:40375186

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12080142/

Abstract

BACKGROUND

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) that can lead to end organ damage and death without treatment. The ability to rapidly distinguish aHUS from other forms of TMA is key for optimal patient management. The PLASMIC Score was developed to identify individuals with thrombotic thrombocytopenic purpura (TTP), a TMA subtype characterized by severe ADAMTS13 deficiency (< 10%), using 7 commonly available laboratory variables and aspects of the patient's medical history. This study aimed to assess the distribution of PLASMIC Scores in patients with known aHUS, and evaluate the utility of the PLASMIC Score in the diagnostic pathway of aHUS in patients with confirmed TMA.

METHODS

Data from eculizumab (NCT01194973) and ravulizumab (NCT02949128) clinical trials were utilized to calculate and evaluate PLASMIC Score distribution in aHUS patients. Real-world patient-level data from the PINC AI™ Healthcare Database (PHD) were used to evaluate the performance of the PLASMIC Score in identifying aHUS in patients with documented TMA diagnoses and renal impairment (primary analysis population; n = 110), and subsequent sensitivity analyses were performed in alternative populations.

RESULTS

A total of 94 aHUS patients from the eculizumab and ravulizumab clinical trials dataset were evaluated; 18/36 (50.0%) and 27/58 (46.6%) patients in the eculizumab and ravulizumab trials, respectively, had a PLASMIC Score of 4, and most patients (~ 85%) had PLASMIC Scores ≤ 5 (range: 3-5), which were distributed similarly between the trials. Among the 110 patients with undifferentiated TMA (primary analysis) from the PHD, a PLASMIC Score cutoff of ≤ 5 yielded sensitivity, specificity and positive predictive value (PPV) and negative predictive values (NPV) of 86.5%, 71.4%, 92.8% and 55.6%, respectively, for identifying probable aHUS. Similar diagnostic performance was observed at a cutoff value of ≤ 5 in further sensitivity analyses. A cutoff value of ≤ 4 yielded a lower PPV (62.9%), yet a higher NPV (85.7%), with only 3 patients misclassified as TTP.

CONCLUSION

Application of the PLASMIC Score in the aHUS diagnostic pathway may support clinical judgement and ascertain confidence in the earlier identification and subsequent treatment of patients with aHUS, thereby improving patient outcomes.

摘要

背景

非典型溶血尿毒综合征（aHUS）是一种血栓性微血管病（TMA），如不进行治疗可导致终末器官损害甚至死亡。快速区分aHUS与其他形式的TMA的能力是优化患者管理的关键。血浆微血管病评分（PLASMIC Score）旨在通过7个常用实验室指标及患者病史特征来识别血栓性血小板减少性紫癜（TTP，一种以严重ADAMTS13缺乏[<10%]为特征的TMA亚型）患者。本研究旨在评估已知aHUS患者的PLASMIC评分分布，并评估PLASMIC评分在确诊TMA患者的aHUS诊断流程中的效用。

方法

利用依库珠单抗（NCT01194973）和ravulizumab（NCT02949128）临床试验数据计算并评估aHUS患者的PLASMIC评分分布。来自PINC AI™医疗保健数据库（PHD）的真实世界患者水平数据用于评估PLASMIC评分在确诊TMA诊断和肾功能损害患者中识别aHUS的性能（主要分析人群；n = 110），并在其他人群中进行后续敏感性分析。

结果

共评估了依库珠单抗和ravulizumab临床试验数据集中的94例aHUS患者；依库珠单抗和ravulizumab试验中分别有18/36（50.0%）和27/58（46.6%）的患者PLASMIC评分为4，且大多数患者（~85%）的PLASMIC评分≤5（范围：3 - 5），两项试验中的分布相似。在PHD中110例未分化TMA患者（主要分析）中，PLASMIC评分临界值≤5时，识别可能aHUS的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）分别为86.5%、71.4%、92.8%和55.6%。在进一步的敏感性分析中，临界值≤5时观察到类似的诊断性能。临界值≤4时PPV较低（62.9%），但NPV较高（85.7%），仅有3例患者被误诊为TTP。