title: Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers.
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 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.
  
  
  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 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).
  
  
  CONCLUSIONS
  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.
authors: Queen Alexandra Hospital, Portsmouth, UK.
authors: Steven
authors: S
authors: Young-Min
authors: Tim
authors: T
authors: Cawston
authors: Nicola
authors: N
authors: Marshall
authors: David
authors: D
authors: Coady
authors: Stephan
authors: S
authors: Christgau
authors: Tore
authors: T
authors: Saxne
authors: Simon
authors: S
authors: Robins
authors: Ian
authors: I
authors: Griffiths
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000652:urine; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D064236:Cartilage Oligomeric Matrix Protein; D024043:Collagen Type II / Q000652:urine*; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D053509:Matrix Metalloproteinase 13 / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D020782:Matrix Metalloproteinases / Q000097:blood; D008875:Middle Aged; D011237:Predictive Value of Tests; D011859:Radiography; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C015484:pyridinoline; C036020:deoxypyridinoline; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1