Background Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA.
Objective To determine the impact of T-cell costimulation modulation in patients with UA or very early RA.
Methods In this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept (∼10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) 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% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. 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 adverse events 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 seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease.
Trial registration number NCT00124449.
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Funding This study was funded by Bristol-Myers Squibb.
Competing interests PE has received consulting fees, lecture fees and research grants from Bristol-Myers Squibb; PD has received lecture fees from Bristol-Myers Squibb; MD has received consulting fees, lecture fees and research grants from Bristol-Myers Squibb; CWL has received corporate funding for research protocols from Bristol-Myers Squibb, UCB Pharma, Pfizer, Roche, Genentech, Amgen, Abbott, Merck and Centocor; J-CB is employed by, and has restricted stocks with, Bristol-Myers Squibb; at the time of submission, GV was employed by, was a holder of a patent with and had stock options with, Bristol-Myers Squibb; HKG has received consulting fees and research grants from Bristol-Myers Squibb, and is a stockholder, board member and consultant to Synarc; CP is an employee of Synarc; PM is employed by BristolMyers Squibb; SO is employed by, and has stock options with, Bristol-Myers Squibb; K Qi is employed by and has stock options with Bristol-Myers Squibb; RW has received consulting fees from Bristol-Myers Squibb and Schering-Plough, a research grant from UCB, and lecture fees from Bristol-Myers Squibb.
Ethics approval Approval was received from several ethics committees. Patient consent Patient consent received.
Provenance and peer review Not commissioned; externally peer reviewed.
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