TY - JOUR
T1 - MRI assessment of early response to certolizumab pegol in rheumatoid arthritis
T2 - a randomised, double-blind, placebo-controlled phase IIIb study applying MRI at weeks 0, 1, 2, 4, 8 and 16
AU - Østergaard, Mikkel
AU - Jacobsson, L T H
AU - Schaufelberger, C
AU - Hansen, Michael Sejer
AU - Bijlsma, J W J
AU - Dudek, A
AU - Rell-Bakalarska, M
AU - Staelens, F
AU - Haake, R
AU - Sundman-Engberg, B
AU - Bliddal, H
N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Objectives To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA). Methods Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400 mg every 2 weeks at weeks 0-4; CZP 200 mg every 2 weeks at weeks 6-16) or placebo→CZP ( placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200 mg every 2 weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures. Results Forty patients were treated (27 CZP, 13 placebo→CZP), and 36 (24 CZP, 12 placebo→CZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group. Conclusions CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials.
AB - Objectives To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA). Methods Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400 mg every 2 weeks at weeks 0-4; CZP 200 mg every 2 weeks at weeks 6-16) or placebo→CZP ( placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200 mg every 2 weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures. Results Forty patients were treated (27 CZP, 13 placebo→CZP), and 36 (24 CZP, 12 placebo→CZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group. Conclusions CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials.
KW - Adult
KW - Antibodies, Monoclonal, Humanized
KW - Arthritis, Rheumatoid
KW - Certolizumab Pegol
KW - Double-Blind Method
KW - Female
KW - Hand Joints
KW - Humans
KW - Immunoglobulin Fab Fragments
KW - Immunosuppressive Agents
KW - Magnetic Resonance Imaging
KW - Male
KW - Middle Aged
KW - Osteitis
KW - Polyethylene Glycols
KW - Synovitis
KW - Treatment Outcome
U2 - 10.1136/annrheumdis-2014-206359
DO - 10.1136/annrheumdis-2014-206359
M3 - Journal article
C2 - 25512675
SN - 0003-4967
VL - 74
SP - 1156
EP - 1163
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 6
ER -