Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis

Rutgeerts, Paul
Sandborn, William J.
Feagan, Brian G.
Reinisch, Walter
Olson, Allan
Johanns, Jewel
Travers, Suzanne
Rachmilewitz, Daniel
Hanauer, Stephen B.
Lichtenstein, Gary R.
de Villiers, Willem J.S.
Present, Daniel
Sands, Bruce E.
Colombel, Jean Frederic.

From the University Hospital Gasthuisberg, Leuven, Belgium (P.R.); Mayo Clinic, Rochester, Minn. (W.J.S.); Robarts Research Institute, University of Western Ontario, London, Ont., Canada (B.G.F.); Universitatsklinik fur Innere Medizin IV, Allgemeines Krankenhaus Wien, Vienna (W.R.); Centocor, Malvern, Pa. (A.O., J.J., S.T.); Shaare Zedak Medical Center, Jerusalem, Israel (D.R.); University of Chicago, Chicago (S.B.H.); University of Pennsylvania, Philadelphia (G.R.L.); University of Kentucky, Lexington (W.J.S.V.); Mount Sinai Medical Center, New York (D.P.); Massachusetts General Hospital, Boston (B.E.S.); and Hopital Huriez-Centre d'Investigation Clinique INSERM Centre Hospitalier et Universitaire de Lille, Lille, France (J.F.C.). Address reprint requests for the Active Ulcerative Colitis Trial 1 (ACT 1) to Dr. Rutgeerts at the Universitaire Ziekenhuizen Leuven, Inwendige Geneeskunde, UZ Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium, or at [email protected]. Address reprint requests for the Active Ulcerative Colitis Trial 2 (ACT 2) to Dr. Sandborn at the Mayo Clinic, 200 First St. SW, Rochester, MN 55905, or at [email protected].

New England Journal of Medicine 353(23):p 2462-2476, December 8, 2005. | DOI: 10.1056/NEJMoa050516

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 lessthan/equal 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.)

N Engl J Med 2005;353

2462-76.