RESEARCHERS have found that undifferentiated arthritis without autoantibodies is more closely linked to joint distribution than generic disease activity, with combined hand and large-joint involvement marking patients at higher risk of progressing to rheumatoid arthritis (RA) in a treat-to-target clinic.
Since the introduction of the 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria, undifferentiated arthritis has become predominantly seronegative and heterogeneous. A subset of patients progresses to RA or remains persistent, yet conventional predictors have proved poorly informative. Before this study, the predictors of persistence in anticitrullinated protein antibody (ACPA)-negative undifferentiated arthritis were poorly defined, particularly under a standardised treat-to-target protocol.
Researchers analysed 402 consecutive patients with ACPA-negative undifferentiated arthritis enrolled in the Pavia Early Arthritis Clinic (2011–2019). Undifferentiated arthritis was defined as clinical synovitis that did not fulfil the 1987 or 2010 RA criteria and had no alternative diagnosis at baseline or within 6 months. All patients started hydroxychloroquine, and escalation was driven by persistent disease activity.
Arthritis was predominantly hand-restricted (75.1%), followed by combined hand and large-joint involvement (19.2%) and isolated large-joint involvement (5.7%). RA developed in 13.1% of patients, while 38.1% developed RA or required treatment intensification.
Combined hand and large-joint arthritis independently predicted RA development (adjusted odds ratio: 2.68; 95% CI: 1.29–5.57) and the composite outcome (adjusted odds ratio: 3.32; 95% CI: 1.77–6.24). C reactive protein (CRP) elevation and pain burden were associated with treatment intensification. Classification tree analysis identified large-joint involvement as the first discriminator; together with the no-large-joint branch with CRP>0.5 mg/dL, it captured 64% of events, with a positive predictive value of 48% and a negative predictive value of 72%.
In contemporary ACPA-negative undifferentiated arthritis, progression has been linked to anatomical joint distribution rather than generic disease activity, with combined hand and large-joint involvement identifying a high-risk phenotype and CRP refining risk in milder branches. Simple baseline anatomical patterns and CRP may help stratify follow-up and treatment escalation when autoantibodies are absent and advanced imaging is not routinely available.
Reference
De Stefano L et al. Frequency and predictors of disease progression in contemporary ACPA-negative undifferentiated arthritis in a treated-to-target early arthritis clinic. RMD Open. 2026;12:e007443.
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