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Impact of intravenous abatacept on synovitis, osteitis and structural damage in patients with rheumatoid arthritis and an inadequate response to methotrexate: the ASSET randomised controlled trial

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Conaghan, Philip G Durez, Patrick [UCL] Alten, Rieke E Burmester, Gerd-Rüdiger Tak, Paul P Peterfy, Charles

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2013
Language Anglais
Journal information "Annals of the Rheumatic Diseases" - Vol. 72, no. 8, p. 1287-1294 (2012)
Peer reviewed yes
Publisher B M J Group ((United Kingdom) London)
issn 0003-4967
e-issn 1468-2060
Publication status Publié
Affiliations UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales
UCL - (SLuc) Service de rhumatologie
MESH Subject Antirheumatic Agents ; Injections, Intravenous ; Magnetic Resonance Imaging ; Male ; Methotrexate ; Middle Aged ; Osteitis ; Synovitis ; Treatment Outcome ; Wrist Joint ; Arthritis, Rheumatoid ; Double-Blind Method ; Drug Resistance ; Drug Substitution ; Drug Therapy, Combination ; Female ; Humans ; Immunoconjugates
Links
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Bibliographic reference Conaghan, Philip G ; Durez, Patrick ; Alten, Rieke E ; Burmester, Gerd-Rüdiger ; Tak, Paul P ; et. al. Impact of intravenous abatacept on synovitis, osteitis and structural damage in patients with rheumatoid arthritis and an inadequate response to methotrexate: the ASSET randomised controlled trial. In: Annals of the Rheumatic Diseases, Vol. 72, no. 8, p. 1287-1294 (2012)
Permanent URL http://hdl.handle.net/2078.1/156560