title: A review of infliximab use in ulcerative colitis.
abstract: BACKGROUND
  Infliximab is a chimeric immunoglobulin G1kappa monoclonal antibody that binds with high affinity and specificity to the soluble form of tumor necrosis factor (TNF)-alpha, preventing it from binding to cellular receptors. Infliximab also binds to membranebound TNF-alpha found on inflammatory cell surfaces, inducing apoptosis. Currently, infliximab is used for the induction and maintenance of remission in Crohn's disease (CD), with documented success. Infliximab's efficacy in the treatment of ulcerative colitis (UC) is now being investigated due to the similarities in the pathophysiology of CD and UC.
  
  
  OBJECTIVE
  The aim of this study was to review and evaluate the current literature of infliximab use in steroid-refractory UC to assess its role in treatment.
  
  
  METHODS
  A search of MEDLINE was conducted (1950-November 2007). Key terms included, but were not limited to, infliximab, inflammatory bowel disease, ulcerative colitis, cost, and quality of life. Studies included for review were limited to English-language, full-text, randomized, double-blind, placebo-controlled trials. Clinical trials were reviewed and summarized.
  
  
  RESULTS
  Four controlled clinical trials of infliximab in the treatment of steroid-refractory UC were found and assessed. In a double-blind, randomized, controlled trial in 43 patients with moderately severe, glucocorticoid-resistant UC, infliximab and placebo were not significantly different with respect to clinical and sigmoidoscopic remission or quality of life 2 and 6 weeks after infliximab treatment. In a multicenter, randomized, double-blind, placebo-controlled study in 45 patients with moderately severe to severe glucocorticoid-resistant UC, infliximab was associated with a significantly reduced need for colectomy compared with placebo (29% vs 67%; P=0.017). The Active Ulcerative Colitis Trials (ACT) 1 and 2 together included 728 patients with moderate to severe glucocorticoid-resistant UC. The primary outcome, the rate of clinical response at 8 weeks, was significantly higher with infliximab compared with placebo (5 mg/kg: ACT 1, 69.4%, ACT 2, 64.5%; 10 mg/kg: ACT 1, 61.5%, ACT 2, 69.2%; placebo: ACT 1, 37.2%;, ACT 2, 29.3%; all, P < 0.001 vs placebo). Based on the data from ACT 1 and 2, infliximab was associated with improved health-related quality-of-life (HRQOL) scores based on the Inflammatory Bowel Disease Questionnaire and the 36-item Short Form Health Survey.
  
  
  CONCLUSIONS
  Current data suggest that infliximab is an effective alternative treatment option for patients with moderate to severe UC with an inadequate response to conventional glucocorticoid treatment. Further trials are needed to assess infliximab's impact on the treatment and progression of UC, the HRQL of patients with UC, and the economic impact on the health care system.
authors.affiliation: Department of Pharmacy Services, Harper University Hospital, Detroit, Michigan, USA.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Wilhelm
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: McKenney
authors.forename: Kelly N
authors.initials: KN
authors.lastname: Rivait
authors.forename: Pramodini B
authors.initials: PB
authors.lastname: Kale-Pradhan
mesh_terms: D000893:Anti-Inflammatory Agents / Q000191:economics / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000191:economics / Q000627:therapeutic use*; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000191:economics / Q000473:pathology / Q000601:surgery; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D004311:Double-Blind Method; D016527:Drug Costs; D004351:Drug Resistance; D005765:Gastrointestinal Agents / Q000191:economics / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000627:therapeutic use; D017048:Health Care Costs; D006801:Humans; D000069285:Infliximab; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D005938:Glucocorticoids; D000069285:Infliximab