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

OBJECTIVES: Anti-TNF therapies are highly effective in rheumatoid (RA) and psoriatic (PsA) arthritis but a significant number of patients exhibit partial or no therapeutic response. Inflammation alters local and systemic metabolism and TNF plays a role in this. We sought 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 and 20 PsA patients before and during therapy with infliximab or etanercept. Urine metabolic profiles were assessed using NMR 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 EULAR criteria, with a sensitivity of 88.9% and specificity of 85.7%, with several metabolites (in particular histamine, glutamine, xanthurenic acid and ethanolamine) contributing. There was a correlation between baseline metabolic profiles and the magnitude of change in DAS 28 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 and 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 optimisation of therapy. Differences in metabolic profiles during treatment with infliximab and etanercept in RA and PsA may reflect distinct mechanisms of action. © 2013 American College of Rheumatology.