title: Durability of infliximab dose intensification in Crohn's disease.
abstract: BACKGROUND
  Dose intensification is a common approach to treat Crohn's disease (CD) patients who lose response to infliximab maintenance therapy. Few studies have reported upon its long-term efficacy or predictors of response.
  
  
  OBJECTIVE
  The goal of this study is to investigate durability and predictors of response to dose intensification-including method of dose intensification, combination immunomodulator therapy, and premedication with intravenous hydrocortisone.
  
  
  METHODS
  We performed a retrospective study of dose-intensified CD patients at our institution. Dose intensification was defined as an increase in dose from 5 to 10 mg/kg, an increase in frequency of infusions from every 8 weeks to every 6 weeks or less, or both an increase in dose and frequency.
  
  
  RESULTS
  Thirty CD patients (mean age, 39.9 years) met study criteria and underwent dose intensification. Ten (33.3%) patients remained on dose intensification at the end of our study or returned to their former infliximab dose or schedule (median follow-up, 41 months). Fourteen patients (46.7%) eventually lost response to dose intensification, but dose intensification extended infliximab therapy by a median duration of 9 months. Six patients (20%) didn't respond to dose intensification. Neither method of dose intensification, combination immunomodulator therapy, nor premedication with intravenous hydrocortisone predicted initial or durable response to dose intensification. However, analysis of predictors was limited by the small sample size of our study.
  
  
  CONCLUSIONS
  The majority of CD patients respond to dose intensification, and a substantial portion will experience durable response such that infliximab therapy is successfully extended by one or more years.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of California at San Francisco, San Francisco, CA, USA. kirk.lin@ucsf.edu
authors.forename: Kirk K
authors.initials: KK
authors.lastname: Lin
authors.forename: Fernando
authors.initials: F
authors.lastname: Velayos
authors.forename: Elena
authors.initials: E
authors.lastname: Fisher
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Terdiman
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
references.citation: J Rheumatol. 2006 Jan;33(1):31-6
references.pmid: 16395747
references.citation: Am J Gastroenterol. 2011 Feb;106(2):199-212; quiz 213
references.pmid: 21045814
references.citation: Inflamm Bowel Dis. 2007 Sep;13(9):1093-9
references.pmid: 17480021
references.citation: Aliment Pharmacol Ther. 2008 Jul;28(2):221-7
references.pmid: 18485127
references.citation: Ann Rheum Dis. 2007 Sep;66(9):1233-8
references.pmid: 17392352
references.citation: Lancet. 2002 May 4;359(9317):1541-9
references.pmid: 12047962
references.citation: Gastroenterology. 2003 Apr;124(4):917-24
references.pmid: 12671888
references.citation: Am J Gastroenterol. 2010 May;105(5):1133-9
references.pmid: 20145610
references.citation: Clin Gastroenterol Hepatol. 2009 Jan;7(1):48-53
references.pmid: 18848909
references.citation: Clin Exp Rheumatol. 2005 Jul-Aug;23(4):469-74
references.pmid: 16095114
references.citation: N Engl J Med. 2010 Apr 15;362(15):1383-95
references.pmid: 20393175
references.citation: Aliment Pharmacol Ther. 2010 Jan;31(1):92-101
references.pmid: 19709098
references.citation: Clin Gastroenterol Hepatol. 2006 Oct;4(10):1248-54
references.pmid: 16931170
references.citation: Aliment Pharmacol Ther. 2007 Dec;26(11-12):1509-20
references.pmid: 17931345
references.citation: N Engl J Med. 2003 Feb 13;348(7):601-8
references.pmid: 12584368
references.citation: Gut. 2009 Apr;58(4):492-500
references.pmid: 18832518
references.citation: Ther Drug Monit. 2008 Aug;30(4):523-9
references.pmid: 18641542
references.citation: Am J Gastroenterol. 2009 Mar;104(3):760-7
references.pmid: 19174781
references.citation: Therap Adv Gastroenterol. 2010 May;3(3):179-89
references.pmid: 21180600
references.citation: World J Gastroenterol. 2008 Nov 21;14(43):6641-7
references.pmid: 19034966
references.citation: Aliment Pharmacol Ther. 2011 Feb;33(3):349-57
references.pmid: 21118397
references.citation: Am J Gastroenterol. 2000 Aug;95(8):1955-60
references.pmid: 10950042
references.citation: Inflamm Bowel Dis. 2008 Mar;14(3):432-4
references.pmid: 18022873
references.citation: Dig Dis Sci. 2008 Apr;53(4):1033-41
references.pmid: 17934827