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To analyse ultrasound (US) differences between rheumatoid arthritis (RA) patients according to autoantibody status and characterise the clinical and radiological features associated with the US pattern of seropositive patients.We collected demographic and clinical data and bilateral hand US images of RA patients. We defined an extreme proliferative US pattern, encompassing synovial hypertrophy grade II-III with Power Doppler signal, which we called US proliferative synovitis (US PS). To better characterise US PS, MRI of the dominant hand and immunostaining of synovial biopsies were made in subgroups of 42 and 23 patients, respectively.We included 205 RA patients (84.8% seropositive). No significant differences in disease activity were found according to autoantibody status. US PS was found in 55.5% of seropositive and 16.1% of seronegative patients (p=0.0001). In the multivariate analysis, erosions [OR 4.90 95% CI (2.17-11.07), p=0.0001] and ACPA [OR 3.5 95% CI (1.39-10.7), p=0.009] but not RF status [OR 0.74 95% CI (0.31-1.71), p=0.483] were independently associated with US PS. After a mean follow-up of 46 months, US PS was independently associated with changes in therapy (OR 2.63, 95% CI 1.20-5.77, p=0.016). Ninety-four per cent of joints with US PS had RAMRIS synovitis sub-index grade 2-3. US PS was significantly associated with higher synovial vessel density (p=0.042).In RA patients, US PS was associated with ACPA status, erosive disease and an enhanced need to change disease-modifying anti-rheumatic drug therapy in the long-term. At synovial level, this US pattern was characterised by higher vessel density.