title: High-dose infliximab therapy in Crohn's disease: clinical experience, safety, and efficacy.
abstract: BACKGROUND
  Inadequate response to infliximab [IFX] therapy in Crohn's disease [CD] may necessitate dose intensification. We evaluated safety and efficacy of high-dose IFX [HD IFX] [greater than 10mg/kg every 8 weeks] in CD and characterized predictors of response to HD IFX intensification.
  
  
  METHODS
  Electronic medical records were queried for CD patients between 2010 and 2012 who received HD IFX and were reviewed for history, medications, laboratory data, efficacy, and safety.
  
  
  RESULTS
  In all, 86 patients received HD IFX for CD at doses between 10 and 22.5mg/kg every 4 to 7 weeks. In early HD IFX therapy [week 1-16], 25.8% and 59.1% experienced full and partial response, respectively. In later HD IFX therapy [week 38-100], 27.9% and 34.4% experienced full and partial response, respectively. Median serum IFX levels increased from 1.7 to 7.3 µ/mL [p = 0.017], and median C-reactive protein [CRP] values decreased from 20.5 at baseline to 4.7 mg/L after 16 weeks [p < 0.001]. Baseline CRP values were significantly elevated in the group that responded at 1-16 weeks compared with nonresponders [22.0 vs 3.5mg/L, p < 0.01]. HD IFX therapy was discontinued in 26% and 7.3% of patients for inadequate response and adverse events, respectively. Eleven cases of infection required hospitalization for a serious infection rate of 7.41 events per 100 patient-years.
  
  
  CONCLUSIONS
  HD IFX therapy may benefit CD patients who have failed standard doses of IFX. HD IFX therapy may be associated with more serious adverse events compared with standard dosing. Baseline CRP value may predict clinical response to HD IFX.
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Hendler
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Cohen
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
authors.affiliation: Division of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
authors.affiliation: Division of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. shradha.agarwal@mssm.edu.
authors.forename: Shradha
authors.initials: S
authors.lastname: Agarwal
mesh_terms: D000293:Adolescent; D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D000069285:Infliximab
keywords: Crohn’s disease; anti-TNF; biologic therapy; dose intensification; infliximab; loss of response