title: Systematic Review: Sequential Rescue Therapy in Severe Ulcerative Colitis: Do the Benefits Outweigh the Risks?
abstract: BACKGROUND
  The options for medical management of acute severe steroid-refractory ulcerative colitis (UC) are limited. Recent guidelines recommend against use of sequential rescue therapy in the setting of failed medical management with initial salvage therapy. A systematic review was conducted to assess outcomes of sequential rescue therapy with infliximab (IFX) and calcineurin inhibitors like cyclosporine (CsA) or tacrolimus (Tac) in patients with steroid-refractory UC.
  
  
  METHODS
  A literature search identified studies that investigated treatment with IFX and CsA or Tac in acute severe UC. Outcomes of interest included short-term symptomatic response to treatment, rates of remission, adverse drug reactions, serious infections, mortality, and colectomy at 3 and 12 months.
  
  
  RESULTS
  Overall, ten studies with 314 participants were eligible for inclusion. After sequential treatment, patients achieved short-term treatment response in 62.4% (95% confidence interval [CI], 57.0%-67.8%) of cases and remission in 38.9% (95% CI, 33.5%-44.3%). Colectomy rates were 28.3% (95% CI, 21.7%-34.5%) at 3 months and 42.3% (95% CI, 36.0%-48.6%) at 12 months. Adverse events were encountered by 23.0% (95% CI, 17.7%-28.3%) of patients, including serious infections in 6.7% (95% CI, 3.6%-9.8%) and mortality in 1% (95% CI, 0%-2.1%).
  
  
  CONCLUSIONS
  The risk of sequential therapy in steroid-refractory UC seems lower than initially reported. Caution must be exercised however because of very low-quality evidence. In contrast to recent guidelines, the current analysis does not support a decision for or against use of sequential rescue therapy, which should only be performed at specialized referral centers familiar with the use of calcineurin inhibition.
authors.affiliation: *Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada; and †Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai Hospital, New York, New York.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Narula
authors.forename: Michael
authors.initials: M
authors.lastname: Fine
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.forename: John K
authors.initials: JK
authors.lastname: Marshall
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
mesh_terms: D003082:Colectomy / Q000379:methods*; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000628:therapy*; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents