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基于司库奇尤单抗治疗银屑病关节炎、强直性脊柱炎和伴有轴性症状的银屑病关节炎的临床开发项目的汇总分析,采用机器学习方法识别的患者聚类。

Patient clusters identified by machine learning from a pooled analysis of the clinical development programme of secukinumab in psoriatic arthritis, ankylosing spondylitis and psoriatic arthritis with axial manifestations.

机构信息

Department of Internal Medicine and Rheumatology, Rheumazentrum Ruhrgebiet, Ruhr University Bochum, Herne, Germany.

Novartis Pharma AG, Basel, Switzerland.

出版信息

Clin Exp Rheumatol. 2024 Mar;42(3):696-701. doi: 10.55563/clinexprheumatol/b8co74. Epub 2023 Nov 28.

DOI:10.55563/clinexprheumatol/b8co74
PMID:38019168
Abstract

OBJECTIVES

To identify patient clusters based on baseline demographics and clinical indicators.

METHODS

Pooled baseline demographics and clinical data of secukinumab-treated patients from ten Phase III studies in psoriatic arthritis (PsA; FUTURE 1-5 and MAXIMISE), ankylosing spondylitis (AS; MEASURE 1-4), were analysed by machine learning (ML) algorithms. The longitudinal responses of secukinumab 300 mg versus 150 mg were investigated across the clusters and three clinical indicators of tender joints, swollen joints and enthesitis.

RESULTS

3907 patients were grouped into eight distinct clusters based on patient demographics and baseline clinical characteristics. Patients with PsA and axial manifestations (MAXIMISE) were overrepresented in clusters 6-8. Patients in cluster 6 (mean age 48 years; 46% male) were overweight with pronounced psoriasis, higher articular burden in knees, shoulders, elbows and wrists. Patients in cluster 7 (mean age 47 years; 53% male) were less overweight with lower polyarticular joint counts and tenderness of the joints of the feet, wrists and hands. Patients in cluster 8 were predominantly with AS (mean age 43 years; 64% male) with a mean body mass index of 27.3 kg/m2, oligoarthritis and high prevalence of spinal pain. Patients with PsA (FUTURE) were overrepresented in clusters 1-5. Longitudinal analysis showed improvements with secukinumab 300 mg versus 150 mg in clusters 6 and 8 for tender joint counts, and cluster 7 for swollen joint counts.

CONCLUSIONS

PsA clusters obtained by ML in pooled dataset indicate phenotypical heterogeneity of patients with PsA and axial manifestations and overlapping features across the spondyloarthritis spectrum.

摘要

目的

根据基线人口统计学和临床指标确定患者聚类。

方法

对来自十个银屑病关节炎(PsA;FUTURE 1-5 和 MAXIMISE)、强直性脊柱炎(AS;MEASURE 1-4)的三期研究中接受司库奇尤单抗治疗的患者的汇总基线人口统计学和临床数据进行机器学习(ML)算法分析。研究了 300mg 和 150mg 司库奇尤单抗在聚类和三个临床指标(压痛关节、肿胀关节和附着点炎)中的纵向反应。

结果

根据患者人口统计学和基线临床特征,3907 名患者分为八个不同的聚类。患有 PsA 和轴性表现(MAXIMISE)的患者在聚类 6-8 中占比较高。聚类 6(平均年龄 48 岁;46%男性)的患者超重,银屑病严重,膝关节、肩部、肘部和手腕的关节负担较高。聚类 7(平均年龄 47 岁;53%男性)的患者超重程度较低,多关节计数较低,足部、手腕和手部关节压痛。聚类 8 的患者主要为 AS(平均年龄 43 岁;64%男性),平均 BMI 为 27.3kg/m2,少关节炎和脊柱疼痛发生率高。FUTURE 中的 PsA 患者在聚类 1-5 中占比较高。纵向分析显示,在聚类 6 和 8 中,300mg 司库奇尤单抗与 150mg 司库奇尤单抗相比,压痛关节计数改善,聚类 7 中,肿胀关节计数改善。

结论

通过 ML 在汇总数据集中获得的 PsA 聚类表明,具有 PsA 和轴性表现的患者存在表型异质性,并且在脊柱关节炎谱中存在重叠特征。

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