Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis
Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis
Abstract & Commentary
By Malcolm Robinson, MD, FACP, FACG, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City. Dr. Robinson serves as a consultant for TAP, Pfizer, Janssen, Eisai, J&J-Merck, and Procter & Gamble, is on the speaker's bureau of Janssen, Eli Lilly, Solvay, TAP, and Aventis, and does research for Forest Labs, Wyeth-Ayerst, AstraZeneca, and Centocor.
Synopsis: Infliximab, an antibody against tumor necrosis factor, is effective in ulcerative colitis.
Source: Rutgeerts P, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462-2476.
Infliximab is a humanized antibody against tumor necrosis factor (TNF) that has been widely utilized in the treatment of rheumatic disorders and Crohn's disease (CD). As is true in CD, large amounts of TNF are found in the blood, colonic lumen, and stools of ulcerative colitis (UC) patients. This international study (conducted in 2 nearly identical parts), authored by a virtual Who's Who in inflammatory bowel disease, involved a total of 728 patients with moderate-to-severe active UC (verified by biopsies). Disease was not controlled in these patients despite steroid and/or immunosuppressive therapy. Patients with positive TB skin tests were excluded. Infliximab was administered IV at weeks 0, 2, 6, 14, and 22 in the second study and also at weeks 30, 38, and 46 in the first of these studies. Combining data from the 2 sub-studies, 67% of patients had a sustained clinical response to 5 mg doses of infliximab vs 33.25% of placebo recipients. 10 mg doses produced sustained clinical response in 65.35% of patients. Remissions were attained in 13.15% of placebo recipients at week 30 compared to about 33% of pooled infliximab recipients. As expected, some patients developed antibodies to infliximab and there were some mostly mild infusion reactions. Mucosal healing occurred in about 60% of infliximab recipients vs about 30% of placebo recipients. Approximately 22% of patients were able to discontinue steroid therapy by the end of the respective study periods. One case of tuberculosis occurred, and one fatal case of histoplasmosis was noted in relation to infliximab treatment.
Commentary
UC can be a dreadful disease with striking morbidity and significant mortality. However, unlike CD, UC can be permanently cured by proctocolectomy. Moreover, a large number of UC patients respond well to conventional therapy including topical and systemic aminosalicylates, topical corticosteroids, brief systemic steroid use, and immunosuppressive agents such as azathioprine and 6-mercaptopurine. There has been great enthusiasm for the use of infliximab in CD, and there is no doubt that it has proved extremely helpful in many seriously ill patients. However, the short and long-term complications of infliximab are still uncertain but nonetheless worrisome. In addition to infusion reactions and life-threatening infections, risk of future malignancy is suspected.
Infliximab therapy is extremely expensive, and it may be likened to having a tiger by the tail in that it may be difficult or impossible to discontinue infliximab therapy once initiated. So, in conclusion, it is good to have yet another option for the treatment of severe and refractory UC. However, let us hope that far better therapies are on the way.
Infliximab, an antibody against tumor necrosis factor, is effective in ulcerative colitis.Subscribe Now for Access
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