Dr. Christgau is the inventor on Nordic Bioscience patents for the CTX-II assays used in this study.
Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers
Version of Record online: 28 SEP 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 56, Issue 10, pages 3236–3247, October 2007
How to Cite
Young-Min, S., Cawston, T., Marshall, N., Coady, D., Christgau, S., Saxne, T., Robins, S. and Griffiths, I. (2007), Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers. Arthritis & Rheumatism, 56: 3236–3247. doi: 10.1002/art.22923
- Issue online: 28 SEP 2007
- Version of Record online: 28 SEP 2007
- Manuscript Accepted: 22 JUN 2007
- Manuscript Received: 11 SEP 2006
- Arthritis Research Campaign clinical fellowship
- Baines Fellowship from the Baines Fund
- Arthritis Research Campaign integrated clinical academic centre grant
To evaluate the performance of biochemical and traditional markers in predicting radiographic progression in rheumatoid arthritis (RA).
One hundred thirty-two patients with early RA were treated with nonbiologic therapies for 2 years and studied longitudinally. Genomic DNA was analyzed for presence of the shared epitope. Levels of matrix metalloproteinases (matrix metalloproteinase 1 [MMP-1], MMP-13, and MMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1), and cartilage oligomeric matrix protein (COMP) were assessed in serially obtained serum samples. The presence of pyridinoline (Pyr), deoxypyridinoline, glycosylated Pyr (Glc-Gal-Pyr), and C-telopeptide of type II collagen (CTX-II) was assessed in urine samples. Radiographs obtained at entry and at 2 years were evaluated using the modified Larsen score.
Baseline and 2-year radiographs were available from 118 patients. Larsen scores worsened during the 2 years in 50 patients, while 68 patients had no radiographic progression. Levels of a variety of biochemical markers, i.e., MMP-3, CTX-II, COMP, TIMP-1, Pyr, and Glc-Gal-Pyr, correlated significantly with radiographic progression at entry and longitudinally as assessed by area under the curve (AUC). By multivariate analysis, a model including MMP-3 and CTX-II was identified as providing the best prediction of radiographic progression at entry (predictive accuracy by receiver operating characteristic [ROC] AUC = 0.76 [95% confidence interval 0.66–0.85]), while a combination of MMP-3, CTX-II, and swollen joint count formed the best longitudinal AUC model (predictive accuracy by ROC AUC = 0.81 [95% confidence interval 0.73–0.89]). Patient-reported measures (Health Assessment Questionnaire, pain scores) were of limited use. In a subset of 50 patients who were treated with methotrexate (MTX) during the followup period, median serum MMP-3 levels decreased after the initiation of MTX therapy (P = 0.0003).
These results indicate that biochemical markers are useful predictors of radiographic progression in RA and that serum MMP-3 levels decrease significantly with MTX therapy. Multivariate models that include MMP-3 and CTX-II perform better than existing traditional markers in predicting radiographic outcome in RA.