Cluster analysis and subphenotype stratification in lupus erythematosus based on data from the Asia Pacific Lupus Collaboration cohort (APLC-CASTLE)

Abstract

<p><strong>Background</strong> Systemic lupus erythematosus (SLE) is a complex disease with heterogenous manifestations.¹ Clinical subphenotypes have been reported, but limited studies have evaluated their long-term impact.² This study utilized the data from the Asia Pacific Lupus Collaboration (APLC) cohort to evaluate subphenotypes in SLE and differences in long term outcome.³</p><p><strong>Methods</strong> Patient data from the APLC cohort collected between 2013 and 2020 were included. Two-step cluster analysis was conducted based on serological features (anti-dsDNA, anti-Sm, anti-phospholipid antibodies, direct coomb’s test, and hypocomplementemia). Clinical characteristics, LLDAS-50 attainment, and risk of damage accrual were compared.</p><p><strong>Results</strong> Three clusters with distinct clinical and serological characteristics were identified (<a href="https://lupus.bmj.com/content/10/Suppl_1/A57#T1">table 1</a>). Cluster one included 1051 patients (29.1%); all patients were positive for anti-dsDNA but negative for other autoantibodies. Patients in cluster one had earlier age of SLE diagnosis and more frequent renal involvement (55.5%). Cluster two included 1537 patients (42.5%); most patients were positive for anti-dsDNA (83.9%) and anti-phospholipid antibodies (57.3%), had more frequent haematological involvements (62.6%) and serositis (19.8%). Cluster three included 1026 patients (28.4%); anti-dsDNA was the only autoantibody found in 474 patients (46.2%) and mucocutaneous involvements were the predominant features (84.5%).</p><p>Over a median of 2.5 years, damage accrual occurred in 20.8% patients and the risk was highest in cluster one (cluster 1 vs cluster 2: OR 1.34, P=0.008; cluster 1 vs cluster 3: OR 1.28, P=0.041). LLDAS-50 was most frequently achieved in cluster three (cluster 1: 49.6%, cluster 2: 48.7%, cluster 3: 59.1%) (<a href="https://lupus.bmj.com/content/10/Suppl_1/A57#F1">figure 1</a>). LLDAS-50 was associated with reduced risk of damage accrual across three clusters (cluster 1: OR 0.71, P=0.032; cluster 2: OR 0.63, P<0.001; cluster 3: OR 0.58, P<0.001).</p><p><strong>Conclusions</strong> Three distinct subphenotypes were confirmed and associated with different risks of damage accrual. LLDAS-50 was an attainable target and associated with reduced risk of damage accrual across three clusters.</p>