Abstract | OBJECTIVES: This randomised, double-blind, placebo-controlled phase IIIb study evaluated the impact of abatacept on MRI pathology as a primary outcome in methotrexate (MTX)-refractory patients with rheumatoid arthritis. METHODS: Patients received intravenous abatacept (∼10 mg/kg) or placebo, on background MTX, for 4 months, followed by an 8-month open-label extension (OLE; all patients received abatacept plus MTX). Patients had 1.5T MRI with intravenous contrast at baseline, Months 4 and 12; wrist synovitis (three locations assessed), and wrist and hand (15 and eight locations assessed, respectively) osteitis and erosion were scored using OMERACT-RAMRIS. RESULTS: 26/27 abatacept- and 23/23 placebo-randomised patients completed Month 4 and entered the OLE; 26 and 21 completed Month 12. The primary endpoint was not achieved; mean change (SD) from baseline in synovitis was -0.44 (1.47) for abatacept versus 0.52 (1.38) for placebo (p=0.103) at Month 4. For mean change in synovitis adjusted for baseline score (sensitivity analysis), the difference between groups was -0.69, p=0.078. Adjusted mean changes (SE) in osteitis and erosion were -1.94 (0.86) and 0.45 (0.43) for abatacept, and 1.54 (0.90) and 0.95 (0.45) for placebo. Further MRI improvements were observed up to Month 12 for abatacept and from Months 4 to 12 for placebo-treated patients switched to abatacept at Month 4. Clinical efficacy was shown with abatacept and sustained to Month 12. CONCLUSIONS: Despite small patient numbers, MRI detected structural and synovial benefit, sustained to Month 12 in abatacept+MTX-treated patients, and improvements in structural and inflammatory outcomes for placebo+MTX-treated patients following addition of abatacept. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT00420199.
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Authors | Philip G Conaghan, Patrick Durez, Rieke E Alten, Gerd-Rüdiger Burmester, Paul P Tak, Lars Klareskog, Anca Irinel Catrina, Julie DiCarlo, Corine Gaillez, Manuela Le Bars, Xianhuang Zhou, Charles Peterfy |
Journal | Annals of the rheumatic diseases
(Ann Rheum Dis)
Vol. 72
Issue 8
Pg. 1287-94
(Aug 2013)
ISSN: 1468-2060 [Electronic] England |
PMID | 22915624
(Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antirheumatic Agents
- Immunoconjugates
- Abatacept
- Methotrexate
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Topics |
- Abatacept
- Antirheumatic Agents
(therapeutic use)
- Arthritis, Rheumatoid
(complications, drug therapy, pathology)
- Double-Blind Method
- Drug Resistance
- Drug Substitution
- Drug Therapy, Combination
- Female
- Humans
- Immunoconjugates
(therapeutic use)
- Injections, Intravenous
- Magnetic Resonance Imaging
- Male
- Methotrexate
(therapeutic use)
- Middle Aged
- Osteitis
(drug therapy, etiology, pathology)
- Synovitis
(drug therapy, etiology, pathology)
- Treatment Outcome
- Wrist Joint
(drug effects, pathology)
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