Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity.
OBJECTIVE
Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts.


METHODS
Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6-12 weeks after initiation of anti-tumor necrosis factor or methotrexate treatment were evaluated by the AUROC.


RESULTS
The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28-CRP (P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6-12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses (P = 0.03) and DAS28-CRP improvement (P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P = 0.02).


CONCLUSIONS
Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an objective measure of RA disease activity to aid in the management of RA in patients with this condition.
UAB Center for Education and Research on Therapeutics, UAB Arthritis Clinical Intervention Program, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, FOT 805D, 510 20th Street South, Birmingham, AL 35294, USA. jcurtis@uab.edu
Jeffrey R
JR
Curtis
Annette H
AH
van der Helm-van Mil
Rachel
R
Knevel
Tom W
TW
Huizinga
Douglas J
DJ
Haney
Yijing
Y
Shen
Saroja
S
Ramanujan
Guy
G
Cavet
Michael
M
Centola
Lyndal K
LK
Hesterberg
David
D
Chernoff
Kerri
K
Ford
Nancy A
NA
Shadick
Max
M
Hamburger
Roy
R
Fleischmann
Edward
E
Keystone
Michael E
ME
Weinblatt
D000328:Adult; D000368:Aged; D000465:Algorithms; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062072:Patient Acuity; D012042:Registries; D015203:Reproducibility of Results; D012219:Rheumatology / Q000379:methods / Q000592:standards; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D018501:Antirheumatic Agents; D015415:Biomarkers; D002097:C-Reactive Protein