title: Effects of adalimumab therapy on disease activity and interferon-γ-mediated biochemical pathways in patients with rheumatoid arthritis.
abstract: In patients with rheumatoid arthritis (RA), overwhelming inflammatory activity and immune activation are indicated by elevated concentrations of immune activation markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and neopterin. Furthermore, accelerated tryptophan (Trp) degradation by the enzyme indoleamine 2,3-dioxygenase (IDO) is detectable in blood samples of patients by an increased kynurenine (Kyn) to Trp ratio (Kyn/Trp). This study comprises 22 patients (20 women, 2 men) with long-standing, moderate to severe RA, who were treated with a monoclonal tumor necrosis factor (TNF)-antibody (Adalimumab 40 mg subcutaneously every other week) in addition to their concomitant, but inadequate anti-rheumatic therapies. Blood samples were collected before therapy and at week 12. ESR and CRP concentrations were measured within routine diagnostic. Serum concentrations of neopterin, Trp, and Kyn were determined by commercially available ELISA and by high performance liquid chromatography. Before therapy, disease activity as reflected by disease activity score 28 (DAS28) was significantly associated with concentrations of inflammation markers such as ESR (rs = 0.601, p < 0.01) and CRP (rs = 0.433, p < 0.05), but not with neopterin concentrations or Trp metabolic changes. Upon treatment, DAS28 improved significantly (median before therapy: 5.7 and after therapy: 3.1; p < 0.0001). During adalimumab treatment, only CRP decreased significantly (p < 0.05), while all other parameters investigated did not change significantly. Our results indicate that anti-TNF therapy does not influence neopterin concentrations or IDO activity in patients with RA, despite a highly significant improvement of patients' disease activity.
authors: Department of General Internal Medicine, Innsbruck Medical University, Innsbruck, Austria.
authors: Katharina
authors: K
authors: Kurz
authors: Manfred
authors: M
authors: Herold
authors: Christiana
authors: C
authors: Winkler
authors: Werner
authors: W
authors: Klotz
authors: Elisabeth
authors: E
authors: Russe
authors: Dietmar
authors: D
authors: Fuchs
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000276:immunology*; D008875:Middle Aged; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000068879:Adalimumab