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

Aim: 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.

Methods: 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.

Results: 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).

Conclusion: 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.