title: Correlation Between Concentrations of Fecal Calprotectin and Outcomes of Patients With Ulcerative Colitis in a Phase 2 Trial.
abstract: OBJECTIVE
  Accurate biomarkers of disease activity and therapeutic response can be valuable for clinical trials. We performed a post hoc analysis of data from a phase 2 trial to assess the relationship between the concentration of fecal calprotectin (FCP) and clinical and endoscopic outcomes of patients with moderate to severe ulcerative colitis receiving tofacitinib.
  
  
  METHODS
  In a double-blind, placebo-controlled, phase 2 trial, 194 patients were assigned randomly to groups given tofacitinib (0.5, 3, 10, or 15 mg twice daily) or placebo. Clinical and endoscopic outcomes were assessed at week 8 using the Mayo scoring system. Receiver operating characteristics were used to evaluate the relationships between FCP concentration and clinical and endoscopic outcomes, and to determine the FCP cut-off concentration that correlated with patient outcome.
  
  
  RESULTS
  Week 8 median concentrations of FCP were significantly lower in responders than in nonresponders (P < .001): clinical response, 156 vs 725 mg/kg; clinical remission, 64 vs 617 mg/kg; endoscopic remission, 44 vs 489 mg/kg; and mucosal healing, 127 vs 753 mg/kg. Area-under-the-curve values for FCP receiver operating characteristic models were 0.80 for clinical remission, 0.81 for endoscopic remission, and 0.78 for mucosal healing. An FCP cut-off value of 150 mg/kg achieved the highest summation of sensitivity and specificity for clinical remission (0.68 and 0.79, respectively; κ coefficient, 0.44) and endoscopic remission (0.79 and 0.75, respectively; κ coefficient, 0.38).
  
  
  CONCLUSIONS
  Concentrations of FCP correlate with clinical and endoscopic outcomes of patients with moderate to severe ulcerative colitis receiving tofacitinib, although at an individual level the agreement was moderate. FCP concentration with a cut-off value of 150 mg/kg had only fair to good accuracy in classifying clinical and endoscopic outcomes in a clinical trial. ClinicalTrials.gov no: NCT00787202.
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, California. Electronic address: wsandborn@ucsd.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Department of Gastroenterology, Barcelona, Spain.
authors.forename: Julian
authors.initials: J
authors.lastname: Panés
authors.affiliation: Pfizer, Inc, Collegeville, Pennsylvania.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Pfizer, Inc, Collegeville, Pennsylvania.
authors.forename: Dahong
authors.initials: D
authors.lastname: Yu
authors.affiliation: Pfizer, Inc, Collegeville, Pennsylvania.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Niezychowski
authors.affiliation: Pfizer, Inc, Collegeville, Pennsylvania.
authors.forename: Chinyu
authors.initials: C
authors.lastname: Su
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000032:analysis; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy*; D003113:Colonoscopy / Q000379:methods; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005243:Feces / Q000737:chemistry*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D012372:ROC Curve; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
keywords: Biomarkers; Endoscopy; Mayo Score; Tofacitinib