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.

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.

• 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)

Chemical References

• Antirheumatic Agents
• Immunoconjugates
• Abatacept
• Methotrexate

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)