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Abstract Number: 2130

Studies of Disease and Therapy-Response Biomarkers in Early Rheumatoid Arthritis Treated with Methotrexate

Aase Haj Hensvold1, Saedis Saevarsdottir*2, Wanyiang Li*3, Vivianne Malmström4, Guy Cavet5, Lars Klareskog6 and Anca Catrina1, 1Department of Medicine, Rheumatology unit, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden, 2Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, 3Crescendo Bioscience Inc. 341 Oyster Point Blvd South San Francisco, CA 94080, San Francisco, CA, 4Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, 5Crescendo Bioscience Inc., South San Francisco, CA, 6Department of Medicine, Rheumatology Unit, Karolinska Institute, Stockholm, Sweden

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: anti-CCP antibodies, methotrexate (MTX) and rheumatoid arthritis (RA)

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Session Information

Title: Rheumatoid Arthritis - Clinical Aspects III: Infections/Risk Factors for Incident Rheumatoid Arthritis/Metrology/Classification/Biomarkers/Predictors of Rheumatolid Arthritis Activity & Severity

Session Type: Abstract Submissions (ACR)

*equally contributed

Background/Purpose: To identify disease and therapy response serum biomarkers in early untreated RA patients started on methotrexate as the only DMARD.

Methods: 186 patients with early treatment naïve RA (symptom disease duration less than 1 year), started on methotrexate (MTX) monotherapy at diagnosis were included in the current study. All patients are part of a larger cohort of early RA named EIRA (epidemiology investigation of rheumatoid arthritis) and had available blood samples at baseline and a median of 3 months after treatment initiation. Concentrations of 12 serum biomarkers were measured at baseline and a median of 3 months after treatment start to calculate multi-biomarker disease activity (MBDA) scores [1]. Additionally ELISA for CCP-2 was performed at baseline. Associations between different biomarkers were calculated using Spearman’s rank correlation. The ability of MBDA score in tracking and differentiating clinical response was estimated by correlation between the change of MBDA score and the change of DAS28ESR from baseline to 3-months visit, and also by calculating area under the ROC curves (AUROCs) for classifying good/moderate EULAR responders versus non-responders at 3-months visit.   

Results:

No differences in the baseline characteristics were observed between patients included in the current study and MTX treated patients in the original large EIRA cohort (n=873) with a median (IQR) age of 52 (42-59), % female of 72%, % anti-CCP positive of 67% and median (IQR) DAS28ESR of 5.7 (5.0-6.2). At 3 months, 29% of the patients were good EULAR responders, 37% were moderate responders and 34% were non-responders. The change of MBDA score from baseline to 3-months visit was significantly correlated with the change of DAS28ESR and able to differentiate EULAR responders and non-responders (AUROC = 0.79, p-value<0.001). The median decrease in the MBDA score was significantly greater in the anti-CCP negative group than in the positive group but correlated with DAS28ESR changes in both groups.

Conclusion:

We confirm the value of MBDA as a surrogate marker for measuring clinical disease activity and differentiate clinical response in early RA patients treated with MTX whether they were anti citrullinated-protein antibodies (ACPA) negative or positive.

 [1] J. R. Curtis, Validation of a Novel Multi-Biomarker Test to Assess Rheumatoid Arthritis Disease Activity, Arthritis Care & Research, accepted, to be online


Disclosure:

A. Haj Hensvold,
None;

S. Saevarsdottir*,
None;

W. Li*,

employment at Crescendo Bioscience,

3;

V. Malmström,
None;

G. Cavet,

Crescendo Bioscience Inc.,

3;

L. Klareskog,
None;

A. Catrina,
None.

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