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.
OBJECTIVE
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.


BACKGROUND
Clinicaltrials.gov NCT00420199.
Section of Musculoskeletal Disease, University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK. p.conaghan@leeds.ac.uk
Philip G
PG
Conaghan
Patrick
P
Durez
Rieke E
RE
Alten
Gerd-Rüdiger
GR
Burmester
Paul P
PP
Tak
Lars
L
Klareskog
Anca Irinel
AI
Catrina
Julie
J
DiCarlo
Corine
C
Gaillez
Manuela
M
Le Bars
Xianhuang
X
Zhou
Charles
C
Peterfy
D000069594:Abatacept; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D004351:Drug Resistance; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D010000:Osteitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013585:Synovitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome; D014955:Wrist Joint / Q000187:drug effects* / Q000473:pathology
D018501:Antirheumatic Agents; D018796:Immunoconjugates; D000069594:Abatacept; D008727:Methotrexate