Abstract

Background: Several agents provide treatment for established RA, but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA.

Methods: In this double-blind, Phase II, placebo-controlled 2-year study, anti-CCP2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of ≥2 joints were randomized to abatacept (~10 mg/kg) or placebo for 6 months, then study drug was terminated. The primary endpoint was development of RA (by ACR criteria) at Year 1. Patients were monitored by radiography, MRI, CCP2, RF, DAS28 and 28-joint count over 2 years.

Results: At Year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference [95% CI] –20.5% [–47.4, 7.8]). Adjusted mean changes from baseline to Year 1 in Genant-modified Sharp radiographic scores for abatacept- versus placebo-treated patients, respectively, were: 0 versus 1.1 for TS, and 0 versus 0.9 for ES. Mean changes from baseline to Year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious AEs occurred in one patient (3.6%) in each group.

Conclusion: Abatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was observed, which was maintained for 6 months after therapy cessation. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease.