Infliximab for the treatment of fistulas in patients with Crohn's disease.

BACKGROUND Enterocutaneous fistulas are a serious complication of Crohn's disease and are difficult to treat. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor alpha, has recently been developed as a treatment for Crohn's disease. We conducted a randomized, multicenter, double-blind, placebo-controlled trial of infliximab for the treatment of fistulas in patients with Crohn's disease. METHODS The study included 94 adult patients who had draining abdominal or perianal fistulas of at least three months' duration as a complication of Crohn's disease. Patients were randomly assigned to receive one of three treatments: placebo (31 patients), 5 mg of infliximab per kilogram of body weight (31 patients), or 10 mg of infliximab per kilogram (32 patients); all three were to be administered intravenously at weeks 0, 2, and 6. The primary end point was a reduction of 50 percent or more from base line in the number of draining fistulas observed at two or more consecutive study visits. A secondary end point was the closure of all fistulas. RESULTS Sixty-eight percent of the patients who received 5 mg of infliximab per kilogram and 56 percent of those who received 10 mg per kilogram achieved the primary end point, as compared with 26 percent of the patients in the placebo group (P=0.002 and P=0.02, respectively). In addition, 55 percent of the patients assigned to receive 5 mg of infliximab per kilogram and 38 percent of those assigned to 10 mg per kilogram had closure of all fistulas, as compared with 13 percent of the patients assigned to placebo (P=0.001 and P=0.04, respectively). The median length of time during which the fistulas remained closed was three months. More than 60 percent of patients in all the groups had adverse events. For patients treated with infliximab, the most common were headache, abscess, upper respiratory tract infection, and fatigue. CONCLUSIONS Infliximab is an efficacious treatment for fistulas in patients with Crohn's disease.

[1]  S. V. van Deventer.  Tumour necrosis factor and Crohn's disease. , 1997, Gut.

[2]  R M Centor,et al.  Choice of long-term strategy for the management of patients with severe esophagitis: a cost-utility analysis. , 1997, Gastroenterology.

[3]  T. Hendrix,et al.  Gastroduodenal Crohn's disease: the focus is on focality. , 1997, Gastroenterology.

[4]  S. Targan,et al.  A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. , 1997, The New England journal of medicine.

[5]  M. Feldmann,et al.  Rheumatoid Arthritis , 1996, Cell.

[6]  D. Hommes,et al.  Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). , 1995, Gastroenterology.

[7]  E. Irvine.  Usual therapy improves perianal Crohn's disease as measured by a new disease activity index. McMaster IBD Study Group. , 1995, Journal of clinical gastroenterology.

[8]  G. Kollias,et al.  The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo. , 1995, Cytokine.

[9]  B. Scallon,et al.  Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. , 1995, Cytokine.

[10]  G. Fick,et al.  Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. , 1995, Annals of internal medicine.

[11]  O. Nielsen,et al.  Cytokines (immunoinflammatory hormones) and their natural regulation in inflammatory bowel disease (Crohn's disease and ulcerative colitis): a review. , 1994, Digestive diseases.

[12]  T. Macdonald,et al.  Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease. , 1994, Gastroenterology.

[13]  B. Scallon,et al.  Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. , 1993, Molecular immunology.

[14]  Z. Cohen,et al.  Combination of Ciprofloxacin and Metronidazole in Severe Perianal Crohn’s Disease , 1993 .

[15]  S. Hanauer,et al.  Rapid closure of Crohn's disease fistulas with continuous intravenous cyclosporin A. , 1993, The American journal of gastroenterology.

[16]  G. Mullin,et al.  Lymphoma in inflammatory bowel disease , 2010, Cancer.

[17]  S. Stephens,et al.  Tumour necrosis factor alpha in stool as a marker of intestinal inflammation , 1992, The Lancet.

[18]  M. Buyse,et al.  Cancer Clinical Trials: Methods and Practice. , 1985 .

[19]  E. Gehan,et al.  Cancer Clinical Trials: Methods and Practice , 1985 .

[20]  L. Brandt,et al.  Metronidazole therapy for perineal Crohn's disease: a follow-up study. , 1982, Gastroenterology.

[21]  J. Coller,et al.  Anal complications in Crohn's disease , 1981, Diseases of the colon and rectum.

[22]  B. Pasternack,et al.  Treatment of Crohn's disease with 6-mercaptopurine. A long-term, randomized, double-blind study. , 1980, The New England journal of medicine.

[23]  L. Brandt,et al.  Healing of perineal Crohn's disease with metronidazole. , 1980, Gastroenterology.

[24]  F Kern,et al.  Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. , 1976, Gastroenterology.