title: Effect of repeated infliximab therapy on serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMP) are involved in the articular tissue destruction processes in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of multiple infusions of infliximab, a chimeric anti-tumor necrosis factor-a (anti-TNF-a) antibody, on concentrations of serum MMP and tissue inhibitors of metalloproteinases (TIMP) in patients with active RA.
  
  
  METHODS
  Patients with RA were scheduled to receive 9 infusions of infliximab (3 mg/kg) at Weeks 0, 2, 6, and every 8 weeks thereafter. The therapy was combined with methotrexate (MTX) (7.5-20 mg/week). Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1, and TIMP-2 were measured by ELISA prior to infusion at Weeks 0, 2, 6, 14, 38, and 62.
  
  
  RESULTS
  The initial infusion of infliximab downregulated serum levels of MMP-1 (p < 0.001), MMP-3 (p < 0.001), MMP-9 (p < 0.001), TIMP-1 (p < 0.01), and TIMP-2 (p < 0.05). The second drug administration caused even more remarkable reduction of measured MMP (p < 0.001 in all cases) but not of TIMP levels. These changes were accompanied by decreased ratios of measured MMP to TIMP. Further infliximab therapy also significantly suppressed serum MMP levels, but was less effective. Before the first infliximab infusion serum concentrations of MMP and TIMP correlated with markers of RA activity such as the Disease Activity Score and C-reactive protein levels. After further drug administrations such associations, although less significant, were also noted.
  
  
  CONCLUSIONS
  Anti-TNF-a antibody therapy combined with MTX resulted in rapid clinical improvement and reduced serum MMP concentrations in patients with RA. Further infusions of infliximab maintained the decrease of MMP, although to a lesser extent than the first and second doses.
authors.affiliation: Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Bialystok, Poland. klimp@amb.edu.pl
authors.forename: Piotr Adrian
authors.initials: PA
authors.lastname: Klimiuk
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Sierakowski
authors.forename: Izabela
authors.initials: I
authors.lastname: Domyslawska
authors.forename: Justyna
authors.initials: J
authors.lastname: Chwiecko
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015536:Down-Regulation / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D000069285:Infliximab; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D008727:Methotrexate