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Cluster analysis in early axial spondyloarthritis predicts poor outcome in the presence of peripheral articular manifestations.

  • Costantino, Félicie1, 2
  • Aegerter, Philippe3, 4
  • Schett, Georg5, 6
  • De Craemer, Ann-Sophie7, 8
  • Molto, Anna9, 10
  • Van den Bosch, Filip7, 8
  • Elewaut, Dirk7, 8
  • Breban, Maxime1, 2
  • D'Agostino, Maria-Antonietta1, 2, 11
  • 1 UVSQ, Inserm U1173, Infection et inflammation, Laboratory of Excellence INFLAMEX, Université Paris-Saclay, Montigny-Le-Bretonneux.
  • 2 Rheumatology Department, AP-HP, Ambroise Paré Hospital, Boulogne-Billancourt.
  • 3 UVSQ, Inserm U1018, CESP, Université Paris-Saclay, Montigny-Le-Bretonneux.
  • 4 GIRCI IdF-UFR Médecine, Paris-Ile-de-France-Ouest Université, Boulogne-Billancourt, France. , (France)
  • 5 Department of Internal Medicine 3-Rheumatology and Immunology.
  • 6 Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen- Nuremberg and Universitatsklinikum Erlangen, Erlangen, Germany. , (Germany)
  • 7 Department of Internal Medicine and Pediatrics, Division of Rheumatology, Ghent University Hospital.
  • 8 Inflammation Research Center, VIB-UGent, Gent, Belgium. , (Belgium)
  • 9 Department of Clinical Epidemiology and Biostatistics, Université de Paris, Inserm U1153.
  • 10 Rheumatology Department, AP-HP, Cochin Hospital, Paris, France. , (France)
  • 11 Rheumatology Unit, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Roma, Italy. , (Italy)
Published Article
Rheumatology (Oxford, England)
Publication Date
Aug 03, 2022
DOI: 10.1093/rheumatology/keab873
PMID: 34864930


To assess whether two cluster analysis-based axial SpA (axSpA) endotypes (A for purely axial; B for both axial and peripheral) are stable over time and are associated with different long-term disease outcomes. K-means cluster analysis was performed at each visit (until 5 years) on 584 patients from the DESIR cohort, who completed all planned visits, and validated in 232 consecutive axSpA patients from the BeGiant cohort. Cluster stability overtime was assessed by kappa statistics. A generalized linear mixed-effect analysis was applied to compare outcomes between clusters. Classification and regression tree (CART) analysis was performed to determine a decision rule able to assign a given patient to a definite cluster at onset. Both endotypes remained remarkably stable over time. In the DESIR cohort, patients in cluster B showed higher disease activity, worse functional outcome and higher need for anti-rheumatic drugs than patients in cluster A. CART analysis yielded three main clinical features (arthritis, enthesitis and dactylitis) that accurately determined cluster assignment. These results could be replicated in the Be-GIANT cohort. Cluster-based axSpA endotypes were reproducible in two different cohorts, stable over time and associated with different long-term outcome. The axSpA endotype with additional peripheral disease manifestations is associated with more severe disease and requires more intensive drug therapy.,, NCT01648907. © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected]

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