Infliximab Maintenance Therapy for Fistulizing Crohn's Disease
Bruce E. Sands, M.D., Frank H. Anderson, M.D., Charles N. Bernstein, M.D., William Y. Chey, M.D., D.Sc., Brian G. Feagan, M.D., Richard N. Fedorak, M.D., Michael A. Kamm, M.D., Joshua R. Korzenik, M.D., Bret A. Lashner, M.D., Jane E. Onken, M.D., Daniel Rachmilewitz, M.D., Paul Rutgeerts, M.D., Ph.D., Gary Wild, M.D., Ph.D., Douglas C. Wolf, M.D., Paul A. Marsters, M.S., Suzanne B. Travers, M.D., Marion A. Blank, Ph.D., and Sander J. van Deventer, M.D., Ph.D.
Background Infliximab, a monoclonal antibody against tumor necrosisfactor, is an effective maintenance therapy for patients withCrohn's disease without fistulas. It is not known whether infliximabis an effective maintenance therapy for patients with fistulas.
Methods We performed a multicenter, double-blind, randomized,placebo-controlled trial to evaluate the efficacy of infliximabmaintenance therapy in 306 adult patients with Crohn's diseaseand one or more draining abdominal or perianal fistulas of atleast three months' duration. Patients received 5 mg of infliximabper kilogram of body weight intravenously on weeks 0, 2, and6. A total of 195 patients who had a response at weeks 10 and14 and 87 patients who had no response were then randomly assignedto receive placebo or 5 mg of infliximab per kilogram everyeight weeks and to be followed to week 54. The primary analysiswas the time to the loss of response among patients who hada response at week 14 and underwent randomization.
Results The time to loss of response was significantly longerfor patients who received infliximab maintenance therapy thanfor those who received placebo maintenance (more than 40 weeksvs. 14 weeks, P<0.001). At week 54, 19 percent of patientsin the placebo maintenance group had a complete absence of drainingfistulas, as compared with 36 percent of patients in the infliximabmaintenance group (P=0.009).
Conclusions Patients with fistulizing Crohn's disease who havea response to induction therapy with infliximab have an increasedlikelihood of a sustained response over a 54-week period ifinfliximab treatment is continued every 8 weeks.
Source Information
From the Gastrointestinal Unit, Massachusetts General Hospital, and Harvard Medical School, Boston (B.E.S.); Department of Medicine, Vancouver Hospital, Vancouver, B.C., Canada (F.H.A.); Section of Gastroenterology, Health Sciences Centre, University of Manitoba, Winnipeg, Canada (C.N.B.); Rochester Institute for Digestive Diseases and Sciences, Rochester, N.Y. (W.Y.C.); Robarts Research Institute, University of Western Ontario, London, Canada (B.G.F.); Division of Gastroenterology, University of Alberta, Edmonton, Canada (R.N.F.); Physiology Unit, St. Mark's Hospital, London, (M.A.K.); Division of Gastroenterology, Washington University School of Medicine, St. Louis (J.R.K.); Department of Gastroenterology, Center for Inflammatory Bowel Disease, Cleveland Clinic Foundation, Cleveland (B.A.L.); Department of Gastroenterology, Duke University Medical Center, Durham, N.C. (J.E.O.); Division of Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (D.R.); Division of Gastroenterology, University Hospital Leuven, Leuven, Belgium (P.R.); Division of Gastroenterology, Montreal General Hospital, Montreal (G.W.); Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Centocor, Malvern, Pa. (P.A.M., S.B.T., M.A.B.); and Afdeling Gastroenterologie, Academisch Medisch Centrum, Amsterdam (S.J.D.).
Address reprint requests to Dr. Sands at the Gastrointestinal Unit, Massachusetts General Hospital, 55 Fruit St., GRJ 7, Boston, MA 02114.
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