title: The engineered human anti-tumor necrosis factor-alpha antibody CDP571 inhibits inflammatory pathways but not T cell activation in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  We investigated the effect of an engineered human anti-tumor necrosis factor-alpha antibody, CDP571, on immune functions as well as bone and cartilage turnover in patients with rheumatoid arthritis (RA) in a placebo controlled trial. We also assessed the effects of repeated treatment with CDP571 in an open label continuation study.
  
  
  METHODS
  Thirty-six patients were treated with either placebo or 0.1, 1, or 10 mg/kg of CDP571 given as an intravenous infusion. The followup period was 8 weeks. Lymphocyte phenotype, soluble CD4 (sCD4), soluble interleukin 2 receptor (sIL-2R), IL-6, and stromelysin levels in the blood were measured before and after treatment; bone and cartilage markers (pyridinoline, deoxypyridinoline, N-terminal telopeptide) were similarly assessed in the urine. Patients who completed a placebo controlled trial of CDP571 were offered further treatment with CDP571. They received a maximum of 2 further doses of 1 mg/kg (7 patients) or 10 mg/kg (9 patients) in an open study.
  
  
  RESULTS
  Plasma IL-6 level was statistically significantly reduced in the 1 and 10 mg/kg groups. In the 10 mg/kg group, there were also reductions in plasma stromelysin and urine bone markers, although there was no change in sCD4 and sIL-2R levels. Repeat doses of CDP571 were well tolerated and continued to suppress the acute phase response and disease activity.
  
  
  CONCLUSIONS
  Treatment with 10 mg/kg of CDP571 reduced IL-6 and surrogate markers of bone turnover in RA, suggesting that CDP571 might prevent joint damage in RA. Since there was no effect on lymphocyte markers despite the marked reduction in inflammation, CDP571 appears to have no effect on ongoing CD4 T cell activation.
authors.affiliation: Department of Clinical and Molecular Rheumatology, The Guy's Hospital Medical and Dental School, London, United Kingdom.
authors.forename: E H
authors.initials: EH
authors.lastname: Choy
authors.forename: E C
authors.initials: EC
authors.lastname: Rankin
authors.forename: D
authors.initials: D
authors.lastname: Kassimos
authors.forename: O
authors.initials: O
authors.lastname: Vetterlein
authors.forename: A
authors.initials: A
authors.lastname: Garyfallos
authors.forename: C T
authors.initials: CT
authors.lastname: Ravirajan
authors.forename: M
authors.initials: M
authors.lastname: Sopwith
authors.forename: R
authors.initials: R
authors.lastname: Eastell
authors.forename: G H
authors.initials: GH
authors.lastname: Kingsley
authors.forename: D A
authors.initials: DA
authors.lastname: Isenberg
authors.forename: G S
authors.initials: GS
authors.lastname: Panayi
mesh_terms: D000906:Antibodies / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D001323:Autoantibodies / Q000032:analysis; D015704:CD4 Antigens / Q000097:blood; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008875:Middle Aged; D010455:Peptides / Q000652:urine; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000097:blood; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D015704:CD4 Antigens; D024042:Collagen Type I; D015850:Interleukin-6; D010455:Peptides; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D019278:Matrix Metalloproteinase 3