CO:02:1 | Frequency and predictors of disease progression in contemporary seronegative undifferentiated arthritis in a treated-to-target early arthritis clinic

Elena Manna¹, Ludovico De Stefano^1|2, Domenico Sorace^1|2, Jacopo Pelizza^1|2, Blerina Xoxi^1|2, Antonio Manzo^1|2, Carlomaurizio Montecucco^1|2, Serena Bugatti^1|2. | ¹Department of Internal Medicine and Therapeutics, University of Pavia; ²Division of Rheumatology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

Background. With the introduction of the 2010 classification criteria for rheumatoid arthritis (RA), the characteristics of undifferentiated arthritis (UA) have shifted towards mostly seronegative, less inflammatory and persistent forms. However, as many as 10-30% of UA patients may still progress to RA or chronic RA-like arthritis. Predictors of disease progression in contemporary UA are at present unexplored. Aim of this study was to analyze the clinical characteristics and outcomes of patients presenting with UA after the introduction of the 2010 criteria.

Methods: The study population was selected from a monocentric inception cohort of patients with new-onset inflammatory arthritis (symptom duration < 12 months; at least 3 swollen joints or, in case of <3 joints, a positive squeeze test or morning stiffness >30 min). After careful exclusion of differential diagnoses, patients classified as UA were followed at 3-month intervals. Treatment with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs; methotrexate -MTX- if not contraindicated) was started in case of persistent disease activity (DAS28 >3.2) and positive judgement of the treating rheumatologist. Outcomes of interest were RA development and/or escalation to a csDMARD within the first 24 months.

Results: Of a total population of 1528 patients enrolled in the years 2011-2019, 431 (28.2%) were diagnosed with UA. Patients were seronegative in 95% of the cases. The vast majority (71.9%) had exclusive involvement of hand joints (wrists and/or small joints, 30% monoarticular), 20.9% had combined involvement of hand and large joints, and the remaining 7.2% had exclusive involvement of large joints (70% monoarticular). During the 24-month observation period, 45 (13.1%) of the 344 patients with complete data for at least 6 months developed RA criteria, and 84/291 additional patients among those remaining UA (28.9%) required escalation to csDMARDs (MTX in 87%). At multivariable analysis, independent predictors of RA or csDMARD start were large joint involvement, raised C-reactive protein (CRP) levels, symmetric arthritis and arthritis of >5 joints. In a classification tree analysis investigating the interrelationship of the individual variables (Figure 1), the most powerful split was involvement of large joints (57.5%), with further increased risk in case of concomitant hand joint arthritis (79.2%). Among patients with exclusive small joint involvement, CRP >0.5 mg/dl was the next split (47.5%) and, in case of normal acute phase reactants, presence of polyarthritis (38%).

Conclusions: Patients with contemporary UA may exhibit chronic disease progression in more than one third of cases. A model including the pattern of joint involvement and acute phase reactants predicts disease outcomes with good accuracy.