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使用来自两项生物初治患者中 Guselkumab 的 III 期临床试验数据,通过机器学习分析鉴定 PsA 表型。

Identification of PsA phenotypes with machine learning analytics using data from two phase III clinical trials of guselkumab in a bio-naïve population of patients with PsA.

机构信息

Rheumatology Department, AP-HP, Lariboisière Hospital, INSERM U1132, Paris, France

Université Paris Cité, Paris, France.

出版信息

RMD Open. 2023 Mar;9(1). doi: 10.1136/rmdopen-2022-002934.

Abstract

OBJECTIVES

Psoriatic arthritis (PsA) phenotypes are typically defined by their clinical components, which may not reflect patients' overlapping symptoms. This post hoc analysis aimed to identify hypothesis-free PsA phenotype clusters using machine learning to analyse data from the phase III DISCOVER-1/DISCOVER-2 clinical trials.

METHODS

Pooled data from bio-naïve patients with active PsA receiving guselkumab 100 mg every 8/4 weeks were retrospectively analysed. Non-negative matrix factorisation was applied as an unsupervised machine learning technique to identify PsA phenotype clusters; baseline patient characteristics and clinical observations were input features. Minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA) low disease activity (LDA) and DAPSA remission at weeks 24 and 52 were evaluated.

RESULTS

Eight clusters (n=661) were identified: cluster 1 (feet dominant), cluster 2 (male, overweight, psoriasis dominant), cluster 3 (hand dominant), cluster 4 (dactylitis dominant), cluster 5 (enthesitis, large joints), cluster 6 (enthesitis, small joints), cluster 7 (axial dominant) and cluster 8 (female, obese, large joints). At week 24, MDA response was highest in cluster 2 and lowest in clusters 3, 5 and 6; at week 52, it was highest in cluster 2 and lowest in cluster 5. At weeks 24 and 52, DAPSA LDA and remission were highest in cluster 2 and lowest in clusters 4 and 6, respectively. All clusters improved with guselkumab treatment over 52 weeks.

CONCLUSIONS

Unsupervised machine learning identified eight PsA phenotype clusters with significant differences in demographics, clinical features and treatment responses. In the future, such data could help support individualised treatment decisions.

摘要

目的

银屑病关节炎(PsA)表型通常通过其临床特征来定义,而这些特征可能无法反映患者重叠的症状。本事后分析旨在使用机器学习分析 III 期 DISCOVER-1/DISCOVER-2 临床试验的数据,以确定无假设的 PsA 表型聚类。

方法

对接受每 8/4 周 100mg 古塞库单抗治疗的初治活动性 PsA 患者的汇总数据进行回顾性分析。应用非负矩阵分解作为一种无监督机器学习技术来识别 PsA 表型聚类;将基线患者特征和临床观察作为输入特征。评估第 24 周和第 52 周时的最小疾病活动度(MDA)、银屑病关节炎疾病活动度指数(DAPSA)低疾病活动度(LDA)和 DAPSA 缓解。

结果

确定了 8 个聚类(n=661):聚类 1(足部为主)、聚类 2(男性、超重、银屑病为主)、聚类 3(手部为主)、聚类 4(指炎为主)、聚类 5(肌腱炎、大关节)、聚类 6(肌腱炎、小关节)、聚类 7(脊柱为主)和聚类 8(女性、肥胖、大关节)。第 24 周时,MDA 反应在聚类 2 中最高,在聚类 3、5 和 6 中最低;第 52 周时,在聚类 2 中最高,在聚类 5 中最低。在第 24 周和第 52 周时,DAPSA LDA 和缓解在聚类 2 中最高,在聚类 4 和 6 中最低。所有聚类在 52 周的古塞库单抗治疗中均得到改善。

结论

无监督机器学习确定了 8 个具有显著差异的 PsA 表型聚类,在人口统计学、临床特征和治疗反应方面存在差异。在未来,此类数据可能有助于支持个体化治疗决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59ef/10069583/b257dfcd5214/rmdopen-2022-002934f01.jpg

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