title: Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory bowel disease: a prospective study.
abstract: BACKGROUND
  Data on the value of therapeutic drug monitoring of infliximab (IFX) to predict mucosal healing (MH) in inflammatory bowel diseases (IBD) are scarce.
  
  
  METHODS
  All consecutive patients with IBD receiving ongoing IFX (5 mg/kg) treatment and developing secondary failure to IFX were enrolled in a prospective study between June 2010 and May 2011. IFX trough levels, antibodies to IFX concentrations, C-reactive protein levels, and fecal calprotectin were measured before IFX optimization and at week 8. A proctosigmoidoscopy was performed on the day of first IFX optimization and at week 8 in all patients with ulcerative colitis (UC). MH was defined by fecal calprotectin <250 μg/g stools in Crohn's disease (CD) and by an endoscopic Mayo score of 0 or 1 in UC.
  
  
  RESULTS
  This study included 52 patients with IBD: 34 patients with CD (mean Crohn's Disease Activity Index, 300; mean C-reactive protein, 28 ± 10 mg/L; mean fecal calprotectin, 705 ± 300 μg/g) and 18 patients with UC (mean Simple Clinical Colitis Activity Index, 7; mean Mayo endoscopic score, 3). After IFX dose intensification, half of CD and UC patients achieved MH. Increase in IFX trough levels (called "delta IFX" in micrograms per milliliter) was associated with MH in both CD and UC (P = 0.001). A delta IFX >0.5 μg/mL was associated with MH (sensitivity [se], 0.88; specificity [sp], 0.77; P = 0.0001, area under the receiver operating characteristic curve, 0.89). On multivariate analysis, the only factor associated with MH after IFX optimization was a delta IFX >0.5 µg/mL (likelihood ratio = 2.02; 95% confidence interval, 1.01-4.08; P = 0.048) in patients with IBD.
  
  
  CONCLUSIONS
  Therapeutic drug monitoring of IFX strongly predicts the likelihood of achieving MH following IFX dose intensification in both CD and UC.
authors.affiliation: *Immunology and Immunomonitoring Department, Laboratoire d'Immunologie et d'Immunomonitoring, CHU de Saint-Etienne, Saint-Étienne, France; †Service de Gastrologie-Entérologie-Hépatologie, CHU de Saint-Etienne, Saint-Étienne, France; ‡Service de Rhumatologie, CHU de Saint-Etienne, Saint-Étienne, France; and §Service de Gastroenterologie, CHU Nancy, Nancy, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Paul
authors.forename: Emilie
authors.initials: E
authors.lastname: Del Tedesco
authors.forename: Hubert
authors.initials: H
authors.lastname: Marotte
authors.forename: Melanie
authors.initials: M
authors.lastname: Rinaudo-Gaujous
authors.forename: Amelie
authors.initials: A
authors.lastname: Moreau
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Phelip
authors.forename: Christian
authors.initials: C
authors.lastname: Genin
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.forename: Xavier
authors.initials: X
authors.lastname: Roblin
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects*; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D005765:Gastrointestinal Agents; D000069285:Infliximab