Work

Frequency and predictors of disease progression in contemporary ACPA-negative undifferentiated arthritis in a treated-to-target early arthritis clinic

Year: 2026

Type: article

Abstract: OBJECTIVES: Since the introduction of the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) criteria, undifferentiated arthritis (UA) has become predominantly seronegative and heterogeneous, with poorly defined predictors of persistence. We assessed rheumatoid arthritis (RA) development and treatment intensification in contemporary anticitrullinated protein antibodies (ACPA)-negative UA managed under a standardised treat-to-target protocol. METHODS: Consecutive ACPA-negative patients with UA enrolled in the Pavia Early Arthritis Clinic (2011–2019) were analysed. UA was defined as clinical synovitis not fulfilling 1987 or 2010 RA criteria and without alternative diagnosis at baseline or within 6 months. All patients started hydroxychloroquine; escalation was driven by persistent disease activity. Outcomes over 24 months were RA development and the composite outcome of RA development or treatment intensification. RESULTS: Among 402 patients, arthritis was predominantly hand-restricted (75.1%), less often combined hand/large-joint (19.2%) or isolated large-joint (5.7%). RA developed in 13.1% of the patients, whereas 38.1% developed RA or required treatment intensification. Combined hand and large-joint arthritis independently predicted RA development (adjusted OR 2.68, 95% CI 1.29 to 5.57) and the composite outcome (adjusted OR 3.32, 95% CI 1.77 to 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/CRP >0.5 mg/dL branch, it captured 64% of events, with positive predictive value 48% and negative predictive value 72%. CONCLUSIONS: In contemporary ACPA-negative UA, progression is driven by anatomical joint distribution rather than generic disease activity. Combined hand/large-joint involvement identifies a high-risk phenotype, while CRP refines risk in clinically milder branches.

Source: RMD Open

DOI: 10.1136/rmdopen-2026-007443