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

ABSTRACT

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL REGISTRATION clinicaltrials.gov, https//clinicaltrials.gov, NCT01648907.