title: ¹H-NMR-Based Metabolomic Study for Identifying Serum Profiles Associated with the Response to Etanercept in Patients with Rheumatoid Arthritis.
abstract: OBJECTIVE
  A considerable proportion of patients with rheumatoid arthritis (RA) do not have a satisfactory response to biological therapies. We investigated the use of metabolomics approach to identify biomarkers able to anticipate the response to biologics in RA patients.
  
  
  METHODS
  Due to gender differences in metabolomic profiling, the analysis was restricted to female patients starting etanercept as the first biological treatment and having a minimum of six months' follow-up. Each patient was evaluated by the same rheumatologist before and after six months of treatment. At this time, the clinical response (good, moderate, none) was determined according to the EUropean League Against Rheumatism (EULAR) criteria, based on both erythrocyte sedimentation rate (EULAR-ESR) and C-reactive protein (EULAR-CRP). Sera collected prior and after six months of etanercept were analyzed by 1H-nuclear magnetic resonance (NMR) spectroscopy in combination with multivariate data analysis.
  
  
  RESULTS
  Twenty-seven patients were enrolled: 18 had a good/moderate response and 9 were non responders according to both EULAR-ESR and EULAR-CRP after six months of etanercept. Metabolomic analysis at baseline was able to discriminate good, moderate, and non-responders with a very good predictivity (Q2 = 0.68) and an excellent sensitivity, specificity, and accuracy (100%). In good responders, we found an increase in isoleucine, leucine, valine, alanine, glutamine, tyrosine, and glucose levels and a decrease in 3-hydroxybutyrate levels after six months of treatment with etanercept with respect to baseline.
  
  
  CONCLUSIONS
  Our study confirms the potential of metabolomic analysis to predict the response to biological agents. Changes in metabolic profiles during treatment may help elucidate their mechanism of action.
authors.affiliation: Department of Internal Medicine and Medical Specialties-Rheumatology Unit, Sapienza University of Rome, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Priori
authors.affiliation: Department of Chemistry-Sapienza University of Rome, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Casadei
authors.affiliation: Department of Chemistry-Sapienza University of Rome, Rome, Italy.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Valerio
authors.affiliation: Department of Internal Medicine and Medical Specialties-Rheumatology Unit, Sapienza University of Rome, Rome, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Scrivo
authors.affiliation: Department of Internal Medicine and Medical Specialties-Rheumatology Unit, Sapienza University of Rome, Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
authors.affiliation: Department of Chemistry-Sapienza University of Rome, Rome, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Manetti
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D000068800:Etanercept / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D055432:Metabolomics; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D018501:Antirheumatic Agents; D000068800:Etanercept