Data-driven identification of subgroups in early rheumatoid arthritis: mortality and cardiovascular disease in a...

To identify subgroups of early rheumatoid arthritis (RA) based on comorbidities and RA manifestations and to investigate their associated risks of cardiovascular events and mortality.

We included patients with incident RA, diagnosed during 2002-2013 and followed through 2022. Latent class analysis was performed using 29 variables (excluding age) to identify subgroups 1 year after RA diagnosis. Risk of major cardiovascular events (4p-MACE), death, acute coronary syndrome and stroke was compared between groups using Cox regression adjusting for age and sex.

Four subgroups were identified in a cohort of 873 patients with early RA: a 'cardiometabolic' group (19%), characterised by a high prevalence of cardiovascular disease (CVD) and diabetes; an 'elderly-onset' group (20%), with a high prevalence of polymyalgia rheumatica, anticitrullinated protein antibodies (ACPAs) negativity and less use of disease-modifying antirheumatic drugs (DMARDs); a 'classic' group (26%) with extensive joint involvement and the highest C reactive protein (CRP) levels and a 'young-onset' group (35%) characterised by ACPA positivity and palindromic arthritis.Compared to the 'young-onset' subgroup, both the 'cardiometabolic' (HR 2.14, 95% CI 1.20 to 3.79) and 'elderly-onset' subgroups (HR 1.89, 95% CI 1.07 to 3.35) had increased MACE risk. However, only the 'cardiometabolic' subgroup had increased mortality risk (HR 1.79, 95% CI 1.12 to 2.87).

Four distinct subgroups were identified with different clinical profiles and outcomes. This underscores the feasibility of data-driven classification in early RA. The 'cardiometabolic' and 'elderly-onset' subgroups had similarly high MACE risk, but the latter used less DMARDs, antihypertensives and statins, suggesting undertreatment of both RA and CVD risk factors.