title: Autoantibodies, metalloproteinases and bone markers in rheumatoid arthritis patients are unable to predict their responses to infliximab.
abstract: OBJECTIVE
  To identify biochemical, immunological and bone markers as predictors of rheumatoid arthritis (RA) patients' responses to infliximab.
  
  
  METHODS
  A total of 76 patients with active RA (American College of Rheumatology criteria), refractory to disease-modifying anti-rheumatic drugs, including methotrexate, received infliximab (3 mg/kg) infusions at weeks 0, 2, 6, and then every 8 weeks in combination with methotrexate or leflunomide. At week 14, infliximab efficacy was evaluated using disease activity score (DAS)28. A serum sample, collected just before starting infliximab, was tested by ELISA (unless stated otherwise) for the following immunological markers: rheumatoid factor by agglutination and ELISA (IgA, IgG and IgM isotypes); anti-cyclic citrullinated protein; autoantibodies recognizing calpastatin domain I and its 27 C-terminal fragment, glucose-6-phosphate isomerase, alpha-enolase; anti-keratin and anti-perinuclear factor antibodies (immunofluorescence); biochemical markers: C-reactive protein (nephelometry), metalloproteinase-1 and -3, tissue inhibitors of metalloproteinases-1 and -2, antioxidants (vitamins A and E; selenium); bone resorption markers: pyridinoline, deoxypyridinoline, osteoprotegerin, soluble receptor activator of nuclear factor-kappaB ligand, cartilage oligomeric matrix protein. Each parameter's predictive value of the response to infliximab was analysed using Fisher's exact, Mann-Whitney and chi-square tests. Hierarchical clustering was performed with The Institute for Genomic Research (TIGR) multiple experiment viewer software.
  
  
  RESULTS
  Good, moderate and non-responder rates were 6.5, 61.8 and 31.5%, respectively. No significant difference was observed between responders and non-responders, regardless of the serum parameters considered. Analysis of dichotomous or continuous variables failed to identify markers predictive of a good or poor response to infliximab.
  
  
  CONCLUSIONS
  The search for soluble markers in RA patients' sera likely to predict response to infliximab because of their involvement in RA pathogenesis seems disappointing. However, because of the limited power to detect smaller differences in biomarkers, the present study is a preliminary exploratory analysis.
authors.affiliation: Department of Rheumatology, Rouen University Hospital, Rouen Cedex, France. thierry.lequerre@univ-rouen.fr
authors.forename: T
authors.initials: T
authors.lastname: Lequerré
authors.forename: F
authors.initials: F
authors.lastname: Jouen
authors.forename: M
authors.initials: M
authors.lastname: Brazier
authors.forename: S
authors.initials: S
authors.lastname: Clayssens
authors.forename: N
authors.initials: N
authors.lastname: Klemmer
authors.forename: J-F
authors.initials: JF
authors.lastname: Ménard
authors.forename: O
authors.initials: O
authors.lastname: Mejjad
authors.forename: A
authors.initials: A
authors.lastname: Daragon
authors.forename: F
authors.initials: F
authors.lastname: Tron
authors.forename: X
authors.initials: X
authors.lastname: Le Loët
authors.forename: O
authors.initials: O
authors.lastname: Vittecoq
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001862:Bone Resorption; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D000069285:Infliximab; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D045726:Metalloproteases / Q000097:blood; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012217:Rheumatoid Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; D012217:Rheumatoid Factor; D000069285:Infliximab; D045726:Metalloproteases; D000077339:Leflunomide; D008727:Methotrexate