Infliximab for induction and maintenance therapy for ulcerative colitis.
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.)
Rutgeerts
Paul
P
University Hospital Gasthuisberg, Leuven, Belgium. paul.rutgeerts@uz.kuleuven.ac.be
Sandborn
William J
WJ
Feagan
Brian G
BG
Reinisch
Walter
W
Olson
Allan
A
Johanns
Jewel
J
Travers
Suzanne
S
Rachmilewitz
Daniel
D
Hanauer
Stephen B
SB
Lichtenstein
Gary R
GR
de Villiers
Willem J S
WJ
Present
Daniel
D
Sands
Bruce E
BE
Colombel
Jean Frédéric
JF
D000328:Adult; D000906:Antibodies / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000145:classification / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007239:Infections / Q000209:etiology; D000069285:Infliximab; D008297:Male; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000906:Antibodies; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab