CHICAGO — Active ulcerative colitis responds to the drug infliximab, according to results of two multicenter phase III trials reported at the annual Digestive Disease Week.
Active Colitis Trial (ACT) 1 and ACT 2 each enrolled 364 patients with moderate or severe ulcerative colitis, refractory to at least one standard therapy.
Investigators randomized patients to receive infliximab at a 5 mg/kg dosage, a 10 mg/kg dosage, or placebo at baseline and at weeks 2 and 6, and then every 8 weeks through week 46.
After 8 weeks of infliximab therapy at either dosage, more than 60% of patients in each trial demonstrated improvement in their symptoms vs. approximately 29% and 37% of placebo-treated patients in ACT 1 and 2, respectively, the authors reported. At 30 weeks, the clinical response was still significantly better in the infliximab groups.
Infliximab also effectively induced remission and led to mucosal healing in patients with active ulcerative colitis, both studies showed.
“This is very encouraging news for a patient population that has few treatment options,” said William Sandborn, M.D., principal investigator of ACT 2 and head of the Mayo Clinic College of Medicine's irritable bowel disease interest group and clinical research unit.
Both ACT 1 and 2 trials had similar results and patient populations, according to Dr. Sandborn, whose institution was one of 55 study centers. He described subjects as outpatients with relatively stable disease.
At enrollment, ACT 1 patients had not responded to treatment with corticosteroids and/or immunosuppressive therapy, whereas patients in ACT 2 had experienced treatment failure with 5-aminosalicylates, steroids, and/or immunosuppressives. The duration of ACT 1 also was longer (54 vs. 30 weeks).
Clinical response was defined as a decrease in the Mayo score of at least 30% and 3 or more points, plus either a reduction of 1 or more points in the rectal bleeding score or a score of 0 or 1 at week 8.
In addition to clinical response, both trials studied clinical remission—a Mayo score of 2 or less, with no individual subscores greater than 1—and mucosal healing, characterized as an endoscopy subscore of 0 or 1.
Remission rates for the drug-treated patients were as high as 39% in ACT 1 (5 mg/kg) at week 8, compared with 15% for placebo. In ACT 1, the difference in the patients' 8-week remission rates between the 10 mg/kg infliximab dosage (32%) and placebo was highly statistically significant, said that trial's lead investigator, Paul Rutgeerts, M.D., from the University Hospital, Leuven, Belgium. Dr. Rutgeerts is a grant recipient of Centocor, the manufacturer of infliximab (Remicade).
Significant differences in remission rates between infliximab and placebo also were evident in ACT 2 and continued at 30 weeks in both trials.
Mucosal healing occurred at week 30 in a higher percentage of patients receiving 10 mg/kg of infliximab than in those with the smaller dosage (50% vs. 49% in ACT 1; 57% vs. 46% in ACT 2). Healing rates for both dosages were significantly higher than for placebo (25% in ACT 1; 30% in ACT 2).
In each study, the proportion of patients who were in remission and able to stop use of corticosteroids after 30 weeks of infliximab therapy was significantly greater for both dosages, compared with placebo.
Dr. Sandborn is also a grant recipient of Centocor.