Investigation of a multi-biomarker disease activity score in rheumatoid arthritis by comparison with magnetic resonance imaging, computed tomography, ultrasonography, and radiography parameters of inflammation and damage.
OBJECTIVE
To investigate the multi-biomarker disease activity (MBDA) score by comparison with imaging findings in an investigator-initiated rheumatoid arthritis (RA) trial (HURRAH trial, NCT00696059).


METHODS
Fifty-two patients with established RA initiated adalimumab treatment and had magnetic resonance imaging (MRI), ultrasonography (US), computed tomography (CT), and radiography performed at weeks 0, 26, and 52. Serum samples were analysed using MBDA score assays and associations between clinical measures, MBDA score, and imaging findings were investigated.


RESULTS
The MBDA score correlated significantly with MRI synovitis (rho = 0.65, p < 0.001), MRI bone marrow oedema (rho = 0.36, p = 0.044), and US power Doppler (PD) score at week 26 (rho = 0.35, p = 0.039) but not at week 0 or week 52. In the 15 patients who had achieved a Disease Activity Score based on C-reactive protein (DAS28-CRP) < 2.6 at week 26, MRI and/or US detected subclinical inflammation and 13 (87%) had a moderate/high MBDA score. For the cohort with available data, none of the four patients in MBDA remission (score ≤ 25) at week 26 had progression of imaging damage from baseline to week 52 whereas progression was observed in three out of nine (33%) and seven out of 21 (33%) patients with moderate (30-44) and high (> 44) MBDA scores, respectively.


CONCLUSIONS
In this cohort, the MBDA score correlated poorly with MRI/US inflammation. However, the MBDA score and MRI/US were generally concordant in showing signs of inflammation in most patients in clinical remission during anti-tumour necrosis factor (anti-TNF) therapy. MBDA scores were elevated in all patients with structural damage progression.
a Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.
S
http://orcid.org/0000-0002-2877-1582
S
Krabbe
b Crescendo Bioscience, Inc , South San Francisco , CA , USA.
R
R
Bolce
a Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.
C H
CH
Brahe
a Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.
U M
UM
Døhn
c Department of Rheumatology , Slagelse Hospital , Slagelse , Denmark.
B J
BJ
Ejbjerg
a Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.|d Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
M L
ML
Hetland
b Crescendo Bioscience, Inc , South San Francisco , CA , USA.
E H
EH
Sasso
b Crescendo Bioscience, Inc , South San Francisco , CA , USA.
D
D
Chernoff
e Clinic of Rheumatology , Private Practice , Roskilde , Denmark.
M S
MS
Hansen
f Department of Infectious Diseases , Copenhagen University Hospital Rigshospitalet , Copenhagen , Denmark.
L S
LS
Knudsen
g Center for Rheumatology and Spine Diseases , Copenhagen University Hospital Gentofte , Gentofte , Denmark.
A
A
Hansen
g Center for Rheumatology and Spine Diseases , Copenhagen University Hospital Gentofte , Gentofte , Denmark.
O R
OR
Madsen
h Gildhøj Private Hospital , Brøndby , Denmark.
M
M
Hasselquist
i Department of Diagnostic Radiology , Copenhagen University Hospital Herlev , Herlev , Denmark.
J
J
Møller
a Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.|d Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
M
M
Østergaard
D000068879:Adalimumab / Q000627:therapeutic use*; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003718:Denmark / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007596:Joints / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000706:statistics & numerical data; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D062072:Patient Acuity; D011859:Radiography / Q000379:methods / Q000706:statistics & numerical data; D012074:Remission Induction; D012107:Research Design / Q000706:statistics & numerical data; D013223:Statistics as Topic; D013585:Synovitis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D014057:Tomography, X-Ray Computed / Q000379:methods / Q000706:statistics & numerical data; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D014463:Ultrasonography / Q000379:methods / Q000706:statistics & numerical data
D018501:Antirheumatic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000068879:Adalimumab; D008727:Methotrexate