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Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers

Young-Min, Steven; Cawston, Tim; Marshall, Nicola; Coady, David; Christgau, Stephan; Saxne, Tore LU ; Robins, Simon and Griffiths, Ian (2007) In Arthritis and Rheumatism 56(10). p.3236-3247
Abstract
Objective. To evaluate the performance of biochemical and traditional markers in predicting radiographic progression in rheumatoid arthritis (RA). Methods. 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 I [MMP-1], MMP-13, and MMP-3), tissue inhibitor of metalloproteinases I (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 11 collagen (CTX-II) was assessed in urine samples.... (More)
Objective. To evaluate the performance of biochemical and traditional markers in predicting radiographic progression in rheumatoid arthritis (RA). Methods. 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 I [MMP-1], MMP-13, and MMP-3), tissue inhibitor of metalloproteinases I (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 11 collagen (CTX-II) was assessed in urine samples. Radiographs obtained at entry and at 2 years were evaluated using the modified Larsen score. Results. 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 Gic-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). Conclusion. 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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis and Rheumatism
volume
56
issue
10
pages
3236 - 3247
publisher
John Wiley & Sons
external identifiers
  • wos:000250264800010
  • scopus:35348910957
ISSN
1529-0131
DOI
10.1002/art.22923
language
English
LU publication?
yes
id
da8f04ec-8c4d-4f38-84ad-b453239d579d (old id 654397)
date added to LUP
2007-12-19 11:38:36
date last changed
2017-10-22 03:52:23
@article{da8f04ec-8c4d-4f38-84ad-b453239d579d,
  abstract     = {Objective. To evaluate the performance of biochemical and traditional markers in predicting radiographic progression in rheumatoid arthritis (RA). Methods. 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 I [MMP-1], MMP-13, and MMP-3), tissue inhibitor of metalloproteinases I (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 11 collagen (CTX-II) was assessed in urine samples. Radiographs obtained at entry and at 2 years were evaluated using the modified Larsen score. Results. 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 Gic-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). Conclusion. 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.},
  author       = {Young-Min, Steven and Cawston, Tim and Marshall, Nicola and Coady, David and Christgau, Stephan and Saxne, Tore and Robins, Simon and Griffiths, Ian},
  issn         = {1529-0131},
  language     = {eng},
  number       = {10},
  pages        = {3236--3247},
  publisher    = {John Wiley & Sons},
  series       = {Arthritis and Rheumatism},
  title        = {Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers},
  url          = {http://dx.doi.org/10.1002/art.22923},
  volume       = {56},
  year         = {2007},
}