Metabolic profiling predicts response to anti-tumor necrosis factor α therapy in patients with rheumatoid arthritis

Sabrina R. Kapoor, Andrew Filer, Martin A. Fitzpatrick, Benjamin A. Fisher, Peter C. Taylor, Christopher D. Buckley, Iain B. McInnes, Karim Raza, Stephen P. Young

Research output: Contribution to journalArticleAcademicpeer-review


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. Conclusion 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. Copyright © 2013 by the American College of Rheumatology.
Original languageEnglish
Pages (from-to)1448-1456
Number of pages9
JournalArthritis and Rheumatism
Issue number6
Publication statusPublished - 1 Jun 2013
Externally publishedYes


  • etanercept
  • ethanolamine
  • glutamine
  • histamine
  • infliximab
  • xanthurenic acid
  • adult
  • article
  • clinical article
  • female
  • human
  • male
  • metabolic parameters
  • metabolomics
  • nuclear magnetic resonance spectroscopy
  • priority journal
  • psoriatic arthritis
  • rheumatoid arthritis
  • sensitivity and specificity
  • treatment response
  • urinalysis


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