Infliximab for induction and maintenance therapy for ulcerative colitis.

Abstract

BACKGROUND:

Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis.

METHODS:

Two randomized, double-blind, placebo-controlled studies--the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively)--evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2.

RESULTS:

In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P< or =0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons).

CONCLUSIONS:

Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.)

• Authors: Paul Rutgeerts, William J Sandborn, Brian G Feagan, Walter Reinisch, Allan Olson, Jewel Johanns, Suzanne Travers, Daniel Rachmilewitz, Stephen B Hanauer, Gary R Lichtenstein, Willem J S de Villiers, Daniel Present, Bruce E Sands, Jean Frédéric Colombel
• Journal: The New England journal of medicine (N Engl J Med) Vol. 353 Issue 23 Pg. 2462-76 (Dec 08 2005) ISSN: 1533-4406 [Electronic] United States
• PMID: 16339095 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2005 Massachusetts Medical Society.

Chemical References

• Antibodies
• Antibodies, Antinuclear
• Antibodies, Monoclonal
• Tumor Necrosis Factor-alpha
• Infliximab

Topics

• Adult
• Antibodies (blood)
• Antibodies, Antinuclear (blood)
• Antibodies, Monoclonal (adverse effects, immunology, therapeutic use)
• Chi-Square Distribution
• Colitis, Ulcerative (classification, drug therapy, immunology)
• Double-Blind Method
• Female
• Humans
• Infections (etiology)
• Infliximab
• Male
• Remission Induction
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)