title: Histological Outcomes and Predictive Value of Faecal Markers in Moderately to Severely Active Ulcerative Colitis Patients Receiving Infliximab.
abstract: OBJECTIVE
  Histological healing has emerged as a promising therapeutic goal in ulcerative colitis. This is especially important in the context of biological therapies. The objectives of the present study were to investigate the ability of infliximab to induce histological remission in ulcerative colitis [UC] patients and to explore the utility of faecal calprotectin and lactoferrin in predicting histological activity.
  
  
  METHODS
  Multi-centre, single-cohort, open-label, 52-week trial including moderately to severely biological-naïve UC patients receiving intravenous infliximab [5mg/kg]. The primary outcome was the proportion of patients with histological remission [Geboes index ≤ 3.0] after 8 weeks of treatment, scored by two independent pathologists.
  
  
  RESULTS
  Twenty patients were included. The rate of histological remission increased from 5% at baseline to 15% and 35% at Week 8 and Week 52, respectively. At Week 8, 40% of patients were in clinical remission [Mayo ≤ 2] and 45% achieved mucosal healing [Mayo endoscopy subscore 0-1]. At Week 52, 25% of patients had clinical, endoscopic and histological remission. Faecal calprotectin and lactoferrin showed the highest correlation with histological activity at Week 8 (area under the curve [AUC] 94%, p = 0.017; and 96%, p = 0.013, respectively) and both markers revealed an excellent positive predictive value for this outcome at this time point [100%, p = 0.017; and 94%, p = 0.013, respectively].
  
  
  CONCLUSIONS
  Infliximab was able to induce histological remission. There was a good agreement between histology and faecal biomarkers. Faecal calprotectin and lactoferrin were good predictors of histological remission. Our data support inclusion of histology as a treatment target complementary to endoscopy in clinical trials when evaluating therapeutic response in UC.
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal fm@med.up.pt.|Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Magro
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Susana Isabel
authors.initials: SI
authors.lastname: Lopes
authors.affiliation: Department of Pathology, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Joanne
authors.initials: J
authors.lastname: Lopes
authors.affiliation: Department of Gastroenterology, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Portela
authors.affiliation: Department of Gastroenterology, Centro Hospitalar do Alto Ave, Guimarães, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Cotter
authors.affiliation: Department of Gastroenterology, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lopes
authors.affiliation: Department of Gastroenterology, Centro Hospitalar do Alto Ave, Guimarães, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Moreira
authors.affiliation: Department of Gastroenterology, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Lago
authors.affiliation: Department of Gastroenterology, Centro Hospitalar Lisboa Oriental Portugal, Lisboa, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Peixe
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Albuquerque
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Rodrigues
authors.affiliation: Department of Pathology, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Mário Rui
authors.initials: MR
authors.lastname: Silva
authors.affiliation: Department of Pathology, Centro Hospitalar do Alto Ave, Guimarães, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Monteiro
authors.affiliation: Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Castro
authors.initials: C
authors.lastname: Lopes
authors.affiliation: Department of Pathology, Centro Hospitalar Lisboa Oriental Portugal, Lisboa, Portugal.
authors.forename: Lucília
authors.initials: L
authors.lastname: Monteiro
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Macedo
authors.affiliation: Clinical Data Unit, Eurotrials Scientific Consultants, Lisboa, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Veloso
authors.affiliation: CIDES Department of Health Information and Decision Sciences, Faculty of Medicine, University of Porto, Porto, Portugal.|CINTESIS, Center for Health Technology and Services Research, Porto, Portugal.
authors.forename: Claudia
authors.initials: C
authors.lastname: Camila
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.|MedInUP Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Afonso
authors.affiliation: Department of Pathology, University Hospital of KU Leuven and UZ Gent, Leuven, Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.affiliation: Department of Pathology, Centro Hospitalar São João, Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto [Ipatimup], University of Porto, Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology*; D005243:Feces / Q000737:chemistry; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D007781:Lactoferrin / Q000032:analysis; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005765:Gastrointestinal Agents; D039841:Leukocyte L1 Antigen Complex; D000069285:Infliximab; D007781:Lactoferrin
keywords: Histopathology; infliximab; ulcerative colitis.