title: Knowledge of Fecal Calprotectin and Infliximab Trough Levels Alters Clinical Decision-making for IBD Outpatients on Maintenance Infliximab Therapy.
abstract: BACKGROUND
  Infliximab is an effective therapy for inflammatory bowel disease (IBD). However, more than 50% of patients lose response. Empiric dose intensification is not effective for all patients because not all patients have objective disease activity or subtherapeutic drug level. The aim was to determine how an objective marker of disease activity or therapeutic drug monitoring affects clinical decisions regarding maintenance infliximab therapy in outpatients with IBD.
  
  
  METHODS
  Consecutive patients with IBD on maintenance infliximab therapy were invited to participate by providing preinfusion stool and blood samples. Fecal calprotectin (FCP) and infliximab trough levels (ITLs) were measured by enzyme linked immunosorbent assay. Three decisions were compared: (1) actual clinical decision, (2) algorithmic FCP or ITL decisions, and (3) expert panel decision based on (a) clinical data, (b) clinical data plus FCP, and (c) clinical data plus FCP plus ITL. In secondary analysis, Receiver-operating curves were used to assess the ability of FCP and ITL in predicting clinical disease activity or remission.
  
  
  RESULTS
  A total of 36 sets of blood and stool were available for analysis; median FCP 191.5 μg/g, median ITLs 7.3 μg/mL. The actual clinical decision differed from the hypothetical decision in 47.2% (FCP algorithm); 69.4% (ITL algorithm); 25.0% (expert panel clinical decision); 44.4% (expert panel clinical plus FCP); 58.3% (expert panel clinical plus FCP plus ITL) cases. FCP predicted clinical relapse (area under the curve [AUC] = 0.417; 95% confidence interval [CI], 0.197-0.641) and subtherapeutic ITL (AUC = 0.774; 95% CI, 0.536-1.000). ITL predicted clinical remission (AUC = 0.498; 95% CI, 0.254-0.742) and objective remission (AUC = 0.773; 95% CI, 0.622-0.924).
  
  
  CONCLUSIONS
  Using FCP and ITLs in addition to clinical data results in an increased number of decisions to optimize management in outpatients with IBD on stable maintenance infliximab therapy.
authors.affiliation: *Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada; †Department of Laboratory Medicine and Pathology, Division of Medical Laboratory Science, University of Alberta, Edmonton, AB, Canada; and ‡Department of Surgery, Division of Surgery, University of Alberta, Edmonton, AB, Canada.
authors.forename: Vivian W
authors.initials: VW
authors.lastname: Huang
authors.forename: Connie
authors.initials: C
authors.lastname: Prosser
authors.forename: Karen I
authors.initials: KI
authors.lastname: Kroeker
authors.forename: Haili
authors.initials: H
authors.lastname: Wang
authors.forename: Carol
authors.initials: C
authors.lastname: Shalapay
authors.forename: Neil
authors.initials: N
authors.lastname: Dhami
authors.forename: Darryl K
authors.initials: DK
authors.lastname: Fedorak
authors.forename: Brendan
authors.initials: B
authors.lastname: Halloran
authors.forename: Levinus A
authors.initials: LA
authors.lastname: Dieleman
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Goodman
authors.forename: Richard N
authors.initials: RN
authors.lastname: Fedorak
mesh_terms: D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D054316:Biomarkers, Pharmacological / Q000032:analysis; D000066491:Clinical Decision-Making / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry*; D005260:Female; D005765:Gastrointestinal Agents / Q000032:analysis* / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D000069285:Infliximab / Q000032:analysis* / Q000627:therapeutic use; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D010045:Outpatients
chemical_list: D054316:Biomarkers, Pharmacological; D005765:Gastrointestinal Agents; D039841:Leukocyte L1 Antigen Complex; D000069285:Infliximab