Infliximab Cuts Ulcerative Colitis Colectomy Rate
PHILADELPHIA — Patients with moderate to severe ulcerative colitis treated with infliximab had their colectomy rate cut by more than a third during the first year of treatment, compared with control patients, according to a review of more than 600 patients enrolled in two pivotal studies.
The results will likely be important for physicians who must decide whether a patient with advanced ulcerative colitis (UC) should start treatment with a biologic drug that blocks tumor necrosis factor-α (TNF-α).
“These are unique data that show we can alter the natural history of the disease,” Dr. Brian G. Feagan said at the annual meeting of the American College of Gastroenterology. It's increasingly understood that colectomy is not a complete solution for advanced UC because of the risks of pouchitis, reduced fecundity, and other complications, added Dr. Feagan, professor of medicine in the gastroenterology service, University of Western Ontario, London.
UC patients “in remission with their colon have a better quality of life” than patients who undergo colectomy, commented Dr. Stephen B. Hanauer, professor of medicine and chief of gastroenterology at the University of Chicago. “Chronically sick patients benefit from colectomy, but the goal of treatment is to get patients in remission and off steroids. Biologic treatments can do this,” he said in an interview.
The new analysis used data collected in the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2), which together compared two dosages of infliximab (either 5 mg/kg or 10 mg/kg) with placebo in two different protocols that treated patients for as long as 54 weeks. The primary finding was that patients treated with either dosage were more likely than placebo patients to have a clinical response after 8, 30, and 54 weeks of treatment (N. Engl. J. Med. 2005;353:2462–76). This led to Food and Drug Administration approval of infliximab (Remicade) for treating moderately to severely active UC.
The ACT 1 and 2 studies were sponsored by Centocor Inc., which markets infliximab in the United States, and by Schering-Plough, which markets the drug in all other countries. Dr. Feagan and Dr. Hanauer receive research support from, and are consultants to and speakers for Centocor.
Data on the incidence of colectomy during the first year of treatment with infliximab were not collected for all patients in the two studies. This information was available from trial records for about half of the patients. Additional information was collected through retrospective contact with patients. About 14% of patients in the study were excluded because no data on their colectomy status were available, leaving 630 patients in the new analysis.
The incidence of colectomies was 9.5% among all patients treated with infliximab during 54 weeks of treatment, compared with a 14.8% rate in the placebo group, a 5.3% absolute cut in the rate of surgery that was statistically significant and a 43% relative reduction, Dr. Feagan said.
Further analysis showed that several patients who received only 30 weeks of placebo treatment by the study protocol were crossed to infliximab during an extension phase. The incidence of either colectomy or the start of infliximab treatment was cut in half in the infliximab-treated patients, compared with the control group.
Infliximab treatment also was linked to significant reductions in hospitalizations for UC, and in surgical and endoscopic procedures of all kinds.
The adverse event profile for infliximab was similar to what was reported in 2005 for the ACT 1 and 2 studies, with no additional cases of tuberculosis, demyelinating disease, or hematologic events, Dr. Feagan said.
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