Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Impact of Abatacept on Synovitis and Structural Damage in Methotrexate (MTX)Inadequate Responders with Active Rheumatoid Arthritis (RA): A Randomized, Controlled Magnetic Resonance Imaging (MRI) Exploratory Study.
Conaghan9, Philip G., Durez8, Patrick, Alten6, Rieke, Burmester4, Gerd, Tak1, Paul P., Klareskog5, Lars, Gaillez2, Corine
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Bristol-Myers Squibb, Rueil-Malmaison, France
Bristol-Myers Squibb, Princeton, NJ
Charité-Universitatsmedizin, Berlin, Germany
Karolinska University Hospital, Stockholm, Sweden
Schlosspark-Klinik, University Medicine Berlin, Germany
Spire Science LCC, San Francisco, CA
Université Catholique de Louvain, Brussels, Belgium
University of Leeds, Leeds, UK
X-ray can detect erosions in established RA, but is less sensitive for early changes1. MRI has the potential to study synovial inflammation and measure bone damage at an earlier stage and with greater sensitivity than X-ray.
Evaluate the impact of abatacept or placebo, + MTX, on MRI changes in wrist synovitis, osteitis and bone erosion in patients with RA and an inadequate response to MTX.
In this double-blind, randomized, Phase IIIb study of abatacept (~10 mg/kg) versus placebo, + MTX, patients had active RA despite MTX, defined as either DAS28 (CRP) >3.2, or >=6 tender and swollen joints and CRP above the upper limit of normal. Patients had clinically detectable synovitis of >=1 wrist, and had >=1 X-ray erosion or were positive for anti-CCP or RF. Patients had 1.5T MRI (coronal fat-suppressed 3D gradient-echo ± IV gadolinium-contrast) of one wrist at baseline and Month 4. The primary endpoint was mean change at Month 4 in wrist synovitis score (OMERACT-RAMRIS method2). Wrist and hand osteitis and erosion scores were secondary endpoints. Exploratory efficacy analyses included DAS28 (CRP), LDAS (<=3.2) and remission (<2.6). Comparisons in wrist synovitis change between groups were based on non-parametric ANCOVA. Efficacy was reported for the intent-to-treat population. Safety was reported for patients who received >=1 abatacept dose.
Of 27 and 23 patients randomized to abatacept + MTX or placebo + MTX, 26 and 23 completed 4 months. Baseline characteristics were generally similar between groups: mean (SD) RA duration was 25.7 (18.0) and 28.2 (17.0) months, and DAS28 scores were 5.3 (1.1) and 5.3 (0.9) for abatacept and placebo, respectively. However, 55.6 and 48.1% of patients in the abatacept and 82.6 and 73.9% in the placebo group were RF and anti-CCP positive, respectively. Mean change from baseline to Month 4 in synovitis score was 0.44 for abatacept and 0.52 for placebo (p=0.103). For osteitis and erosion scores, mean changes were 1.94 and 0.45 for abatacept versus 1.54 and 0.95 for placebo (treatment difference [95% CI]: 0.50 [1.77, 0.76] and 3.48 [6.00, 0.96], respectively). The percentage of patients with newly involved joints at Month 4, by synovitis, osteitis and erosion scores was 8, 28 and 20% for abatacept versus 13, 30 and 30% for placebo. At Month 4, mean (95% CI) change from baseline in DAS28 was 1.68 (2.15, 1.21) for abatacept and 0.55 (0.95, 0.16) for placebo. Percentages (95% CI) of patients with LDAS and remission were 50.0 (30.8, 69.2) and 15.4% (1.5, 29.3) in the abatacept and 13.6 (0.0, 28.0) and 0.0% (0.0, 0.0) in the placebo group. Safety events were similar to previously reported abatacept trials.
The sensitivity of MRI is again demonstrated, in that even with small patient numbers and wrist-only assessments, abatacept + MTX treatment was associated with reductions in osteitis and erosion scores, and a trend toward reduced MRI synovitis scores versus placebo + MTX. The beneficial clinical outcomes were consistent with those in other large-scale abatacept clinical trials.
To cite this abstract, please use the following information:
Conaghan, Philip G., Durez, Patrick, Alten, Rieke, Burmester, Gerd, Tak, Paul P., Klareskog, Lars, et al; Impact of Abatacept on Synovitis and Structural Damage in Methotrexate (MTX)Inadequate Responders with Active Rheumatoid Arthritis (RA): A Randomized, Controlled Magnetic Resonance Imaging (MRI) Exploratory Study. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1817