PHILADELPHIA -- Ulcerative colitis patients had up to a 50% reduction in colectomy risk at one year when treated with infliximab (Remicade), found pooled results of trials at two doses.
PHILADELPHIA, Oct. 17 -- Ulcerative colitis patients had up to a 50% reduction in colectomy risk at one year when treated with infliximab (Remicade), found pooled results of trials at two doses.
Combining results of the two placebo-controlled trials of the TNF-a inhibitor yielded an overall risk reduction of 36%, Brian G. Feagan, M.D., of the University of Western Ontario in Hamilton, reported at the American College of Gastroenterology meeting here. Treatment with the higher dose halved the one-year rate.
Infliximab also significantly reduced the proportion of patients requiring ulcerative colitis hospitalization and reduced related procedures compared with placebo in patients with moderate to severe disease, said Dr. Feagan.
The findings came from an analysis of data from the Active Ulcerative Colitis Trial (ACT) 1 and ACT 2. The trials involved a combined total of 728 patients with moderate to severe ulcerative colitis (defined as a Mayo Clinic score of 6 to 12) and unresponsive to or intolerant to at least one standard therapy.
The patients were randomized to placebo or to 5 mg/kg or 10 mg/kg of infliximab. Treatment began at baseline, two weeks, and six weeks, and then every eight weeks until week 22 in ACT 2 and to week 46 in ACT 1.
Upon completion of randomized therapy, patients could enter an open-label extension phase, if their physicians considered additional treatment worthwhile. A total of 229 patients from the two trials received extension therapy (infliximab or placebo), which was administered every eight weeks at the same dose the patient received during randomized treatment.
The investigators had complete data on 86% of the original 728 patients, Dr. Feagan reported. The primary endpoint of the analysis was the time to colectomy during follow-up to 54 weeks.
A total of 82 patients had colectomies, 28 in the 5 mg/kg infliximab group, 18 in the 10 mg/kg group, and 36 in the placebo group. Combined data on all infliximab patients demonstrated a colectomy rate of 9.5% compared with 14.8% for the placebo group (P=0.035). Treatment with infliximab significantly delayed the time to colectomy compared with placebo (P=0.015).
Infliximab therapy was associated with a 50% reduction in hospitalizations related to ulcerative colitis, and the difference from placebo was similar whether infliximab dose groups were considered individually or combined (P=0.019 to P=0.003).
The number of colitis-related operations or procedures was 35% to 45% lower among infliximab patients. The difference was statistically significant compared with placebo for the higher dose (P=0.022) and for the two dose groups combined (P=0.026).
Adverse event data for ACT 1 and ACT 2 have been reported previously (N Engl J Med 2005;353:2462-2476). No new or unexpected adverse events have occurred with longer follow-up, said Dr. Feagan.