Colectomy Rate Comparison After Treatment of Ulcerative Colitis With Placebo or Infliximab

Gastroenterology. 2009 Oct;137(4):1250-60; quiz 1520. doi: 10.1053/j.gastro.2009.06.061. Epub 2009 Jul 28.

Abstract

Background & aims: The efficacy of infliximab for treating patients with ulcerative colitis has been established.

Methods: The Active Ulcerative Colitis Trial (ACT)-1 and ACT-2 randomized, double-blind, placebo-controlled studies evaluated infliximab induction and maintenance therapy in moderately to severely active ulcerative colitis. Overall, 728 patients received placebo or infliximab (5 or 10 mg/kg) intravenously at weeks 0, 2, and 6, then every 8 weeks through week 46 (ACT-1) or 22 (ACT-2). Colectomy, hospitalization, and surgery/procedure data through 54 weeks after the first infusion were obtained from ACT-1, ACT-2, and associated data sources. In the prespecified analysis, all data were combined to ascertain time to colectomy. Kaplan-Meier product-limit method was used to estimate the cumulative incidence of colectomy, and log-rank test was used to compare the combined infliximab group and placebo.

Results: Eighty-seven percent (630 of 728) of patients had complete colectomy follow-up; 13% (98 of 728) of patients had a median follow-up of 6.2 months. The cumulative incidence of colectomy through 54 weeks was 10% for infliximab and 17% for placebo (P = .02), yielding an absolute risk reduction of 7%. Compared with placebo, fewer ulcerative colitis-related hospitalizations and surgeries/procedures per 100 patient-years of treatment occurred with infliximab therapy: 40 vs 20 (P = .003) and 34 vs 21 (P = .03), respectively. Serious adverse events occurring in infliximab-treated patients included serious infections, tuberculosis, histoplasmosis, listeriosis, and malignancy.

Conclusions: Patients with moderately to severely active ulcerative colitis treated with infliximab were less likely to undergo colectomy through 54 weeks than those receiving placebo.

Trial registration: ClinicalTrials.gov NCT00036439 NCT00096655 NCT00207688.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Colectomy / statistics & numerical data*
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / surgery*
  • Double-Blind Method
  • Drug Administration Schedule
  • Europe
  • Female
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / therapeutic use*
  • Hospitalization
  • Humans
  • Infliximab
  • Injections, Intravenous
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • North America
  • Proportional Hazards Models
  • Risk Assessment
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Gastrointestinal Agents
  • Infliximab

Associated data

  • ClinicalTrials.gov/NCT00036439
  • ClinicalTrials.gov/NCT00096655
  • ClinicalTrials.gov/NCT00207688