Abatacept reduces disease activity and ultrasound power Doppler in ACPA-negative undifferentiated arthritis: a proof-of-concept clinical and imaging study

Objectives: No proven treatment exists for anti-citrullinated peptide antibody (ACPA)-negative undifferentiated arthritis (UA). This study evaluated whether abatacept is effective in poor prognosis, ACPA-negative UA including its effect on ultrasound power Doppler (US PD) Methods: A proof of concept, open-label, prospective study of 20 patients with DMARD-naïve, ACPA negative UA (≥ 2 joint synovitis) and PD ≥ 1 with clinical and 20 joint US [Grey Scale (GS)/PD] assessments at baseline, 6, 12, 18 and 24 months. All patients received 12 months of abatacept (monotherapy for minimum first 6 months). Primary endpoint was a composite of the proportion of patients that at 6 months achieved DAS44 remission, maximum of one swollen joint for at least 3 consecutive months and no radiographic progression (0-12months). Results: 20/23 patients screened were enrolled [14 female; mean (SD) age 53.4 (11.2) years, symptom duration 7.5 (0.9) months]. Two (10%) achieved the composite primary endpoint. Reduction in mean(SD) DAS44 was observed from baseline value of 2.66(0.77) to 2.01(0.81) at 6 months and to 1.78(0.95) at 12 months. DAS44 remission rates were 6/20 (30%; 95%CI 15%, 51%) at 6 months and 8/20 (40%; 95%CI 22%,62%) at 12 months. A striking decrease in median(IQR) total PD score was noted from 10(4,23) at baseline to 3(2,12) and 3(0,5) at 6 and 12 months respectively. Conclusions: This report is a first in potentially identifying an effective therapy, abatacept monotherapy, for poor prognosis ACPA negative UA, supported by a clear reduction in US PD. These data justify evaluation in a controlled study.