title: Development and Internal Validation of a Model Using Fecal Calprotectin in Combination with Infliximab Trough Levels to Predict Clinical Relapse in Crohn's Disease.
abstract: The best noninvasive method predicting clinical relapse remains undetermined in infliximab (IFX)-treated patients with Crohn's disease.
  
  
  
  All patients with CD on IFX maintenance treatment and in clinical remission for at least 16 weeks, between 2011 and 2014, were enrolled in a prospective single-center study. The Crohn's Disease Activity Index (CDAI), fecal calprotectin, C-reactive protein levels, antibodies (ATI), and trough level (TLI) of IFX were measured at every IFX infusion. The best thresholds of TLI (2 versus 3 μg/mL) and calprotectin (50 versus 250 μg/g stools) were identified across four logistic regression models.
  
  
  
  One hundred nineteen patients (mean age: 34 ± 12 yrs, mean disease duration: 7.8 yrs) were included. Mean follow-up was 20.4 months, and 17% of the patients were on IFX and azathioprine at inclusion. During follow-up, 37 patients (31.1%) relapsed, 78% within the first 6 months. The clinical characteristics of the relapsed and nonrelapsed patients were similar. After logistic regression, fecal calprotectin >250 μg/g stools (OR: 4.09; 95% CI, 1.01-16.21; P = 0.049) and TLI <2 μg/mL (OR: 14.85; 95% CI, 3.67-60; P < 0.0001) were associated with loss of response. A training cohort of 55 patients was isolated randomly to implement prediction rules for loss of response. The best predictive rules were the combination of a TLI <2 μg/mL and a fecal calprotectin level >250 μg/g stools (78.3%). These rules were validated on a test cohort of 64 patients with an accuracy of 87%, (sensitivity = 0.94, specificity = 0.84, positive predictive value = 0.73, and negative predictive value = 0.97).
  
  
  
  In IFX-treated patients with CD in clinical remission, a combination of TLI (<2 μg/mL) and fecal calprotectin (>250 μg/g of stools) is a good model for predicting loss of response. In contrast with previous data, low TLIs ranging from 2 to 3 μg/mL should neither systematically lead to the optimization of IFX use nor a switch in the treatment.
authors.affiliation: *Department of Gastroenterology, University Hospital of Saint Etienne, France; †Mathematic Unit, University Claude Bernard, Lyon, France; ‡Department of Radiology, University Hospital of Saint Etienne, France; §Department of Gastroenterology, CHU, Lyon Sud, Lyon, France; ‖Department of Gastroenterology and Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-les-Nancy, France; and ¶Department of Immunology, University Hospital of Saint Etienne, Saint Etienne, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Roblin
authors.forename: Gerard
authors.initials: G
authors.lastname: Duru
authors.forename: Nicolas
authors.initials: N
authors.lastname: Williet
authors.forename: Emilie
authors.initials: E
authors.lastname: Del Tedesco
authors.forename: Murielle
authors.initials: M
authors.lastname: Cuilleron
authors.forename: Camille
authors.initials: C
authors.lastname: Jarlot
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Phelip
authors.forename: Gilles
authors.initials: G
authors.lastname: Boschetti
authors.forename: Bernard
authors.initials: B
authors.lastname: Flourié
authors.forename: Stephane
authors.initials: S
authors.lastname: Nancey
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.forename: Stephane
authors.initials: S
authors.lastname: Paul
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage; D002097:C-Reactive Protein / Q000032:analysis; D003424:Crohn Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D005243:Feces / Q000737:chemistry*; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000097:blood*; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage / Q000097:blood*; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D016015:Logistic Models; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D039841:Leukocyte L1 Antigen Complex; D002097:C-Reactive Protein; D000069285:Infliximab; D001379:Azathioprine