title: An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis.
abstract: OBJECTIVE
  Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect.
  
  
  METHODS
  We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n = 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n = 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods.
  
  
  RESULTS
  There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P = .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P = .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P = .003) and the accelerated dosing regimen (P = .03).
  
  
  CONCLUSIONS
  In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.
authors.affiliation: Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. Electronic address: gibsond@tcd.ie.
authors.forename: David J
authors.initials: DJ
authors.lastname: Gibson
authors.affiliation: Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Zaid S
authors.initials: ZS
authors.lastname: Heetun
authors.affiliation: Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Ciaran E
authors.initials: CE
authors.lastname: Redmond
authors.affiliation: Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Kavin S
authors.initials: KS
authors.lastname: Nanda
authors.affiliation: Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Denise
authors.initials: D
authors.lastname: Keegan
authors.affiliation: Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Byrne
authors.affiliation: Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Hugh E
authors.initials: HE
authors.lastname: Mulcahy
authors.affiliation: Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Garret
authors.initials: G
authors.lastname: Cullen
authors.affiliation: Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Glen A
authors.initials: GA
authors.lastname: Doherty
mesh_terms: D000328:Adult; D000818:Animals; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D060828:Induction Chemotherapy / Q000379:methods*; D000069285:Infliximab / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D000069285:Infliximab
keywords: Accelerated Induction; Infliximab; Ulcerative Colitis