title: Review article: dose optimisation of infliximab for acute severe ulcerative colitis.
abstract: Although optimal medical management of acute severe ulcerative colitis (UC) is ill-defined, infliximab has become a standard of care. Accumulating evidence suggests an increased rate of infliximab clearance in patients with acute severe UC and a reduced colectomy rate with an intensified infliximab induction regimen.
  
  
  
  To assess the strength of the current evidence for the relationship between infliximab pharmacokinetics, dosing strategies and disease behaviour in patients with acute severe UC.
  
  
  
  We systematically searched MEDLINE and conference proceedings from 2000 to 2016 for relevant articles describing the pharmacokinetics of infliximab in acute severe UC and/or infliximab dose intensification strategies in acute severe UC. Eligible articles described randomised controlled trials, and cohort, cross-sectional, and case-controlled studies.
  
  
  
  Of 400 citations identified, 76 studies were eligible. Increased infliximab clearance occurs in patients with acute severe UC, and is driven by the total inflammatory burden and leakage of drug into the colonic lumen. Several cohort studies suggest that infliximab dose intensification is beneficial to at least 50% of acute severe UC patients and the results of case-controlled studies indicate that an intensified infliximab dosing regimen with 1-2 additional infusions in the first 3 weeks of treatment could reduce the early (3-month) colectomy rate by up to 80%, although these data require prospective validation.
  
  
  
  Uncontrolled studies suggest a benefit for infliximab dose optimisation in patients with acute severe UC. A randomised controlled trial in acute severe UC patients comparing a personalised infliximab dose-optimisation strategy with conventional dosing is a research priority.
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Department of Gastroenterology, University of Ghent, Ghent, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Hindryckx
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Department of Gastroenterology, Ljubljana University Medical Centre, Ljubljana, Slovenia.
authors.forename: G
authors.initials: G
authors.lastname: Novak
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Vande Casteele
authors.affiliation: Department of Gastroenterology, University of Ghent, Ghent, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Laukens
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Parker
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Shackelton
authors.affiliation: Department of Medicine and Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Narula
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Department of Medicine, University of Western Ontario, London, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Khanna
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
authors.forename: P
authors.initials: P
authors.lastname: Dulai
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Levesque
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Department of Medicine, University of Western Ontario, London, Ontario, Canada.|Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada.
authors.forename: B G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Department of Medicine, University of Western Ontario, London, Ontario, Canada.|Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Jairath
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000069285:Infliximab