title: Metabolic profiling predicts response to anti-tumor necrosis factor α therapy in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Anti-tumor necrosis factor (anti-TNF) therapies are highly effective in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), but a significant number of patients exhibit only a partial or no therapeutic response. Inflammation alters local and systemic metabolism, and TNF plays a role in this. We undertook this study to determine if the patient's metabolic fingerprint prior to therapy could predict responses to anti-TNF agents.
  
  
  METHODS
  Urine was collected from 16 RA patients and 20 PsA patients before and during therapy with infliximab or etanercept. Urine metabolic profiles were assessed using nuclear magnetic resonance spectroscopy. Discriminating metabolites were identified, and the relationship between metabolic profiles and clinical outcomes was assessed.
  
  
  RESULTS
  Baseline urine metabolic profiles discriminated between RA patients who did or did not have a good response to anti-TNF therapy according to European League Against Rheumatism criteria, with a sensitivity of 88.9% and a specificity of 85.7%, with several metabolites contributing (in particular histamine, glutamine, xanthurenic acid, and ethanolamine). There was a correlation between baseline metabolic profiles and the magnitude of change in the Disease Activity Score in 28 joints from baseline to 12 months in RA patients (P = 0.04). In both RA and PsA, urinary metabolic profiles changed between baseline and 12 weeks of anti-TNF therapy. Within the responders, urinary metabolite changes distinguished between etanercept and infliximab treatment.
  
  
  CONCLUSIONS
  The clear relationship between urine metabolic profiles of RA patients at baseline and their response to anti-TNF therapy may allow development of novel approaches to the optimization of therapy. Differences in metabolic profiles during treatment with infliximab and etanercept in RA and PsA may reflect distinct mechanisms of action.
authors: University of Birmingham and the Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.
authors: Sabrina R
authors: SR
authors: Kapoor
authors: Andrew
authors: A
authors: Filer
authors: Martin A
authors: MA
authors: Fitzpatrick
authors: Benjamin A
authors: BA
authors: Fisher
authors: Peter C
authors: PC
authors: Taylor
authors: Christopher D
authors: CD
authors: Buckley
authors: Iain B
authors: IB
authors: McInnes
authors: Karim
authors: K
authors: Raza
authors: Stephen P
authors: SP
authors: Young
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D004739:England; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D000069285:Infliximab; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept