A Short-Term Study of Chimeric Monoclonal Antibody cA2 to Tumor Necrosis Factor for Crohn's Disease
Stephan R. Targan, M.D., Stephen B. Hanauer, M.D., Sander J.H. van Deventer, M.D., Ph.D., Lloyd Mayer, M.D., Daniel H. Present, M.D., Tanja Braakman, M.D., Kimberly L. DeWoody, M.S., Thomas F. Schaible, Ph.D., Paul J. Rutgeerts, M.D., Ph.D., for The Crohn's Disease cA2 Study Group
Background Studies in animals and an open-label trial have suggesteda role for antibodies to tumor necrosis factor , specificallychimeric monoclonal antibody cA2, in the treatment of Crohn'sdisease.
Methods We conducted a 12-week multicenter, double-blind, placebo-controlledtrial of cA2 in 108 patients with moderate-to-severe Crohn'sdisease that was resistant to treatment. All had scores on theCrohn's Disease Activity Index between 220 and 400 (scores canrange from 0 to about 600, with higher scores indicating moresevere illness). Patients were randomly assigned to receivea single two-hour intravenous infusion of either placebo orcA2 in a dose of 5 mg per kilogram of body weight, 10 mg perkilogram, or 20 mg per kilogram. Clinical response, the primaryend point, was defined as a reduction of 70 or more points inthe score on the Crohn's Disease Activity Index at four weeksthat was not accompanied by a change in any concomitant medications.
Results At four weeks, 81 percent of the patients given 5 mgof cA2 per kilogram (22 of 27 patients), 50 percent of thosegiven 10 mg of cA2 per kilogram (14 of 28), and 64 percent ofthose given 20 mg of cA2 per kilogram (18 of 28) had had a clinicalresponse, as compared with 17 percent of patients in the placebogroup (4 of 24) (P<0.001 for the comparison of the cA2 groupas a whole with placebo). Thirty-three percent of the patientsgiven cA2 went into remission (defined as a score below 150on the Crohn's Disease Activity Index), as compared with 4 percentof the patients given placebo (P = 0.005). At 12 weeks, 41 percentof the cA2-treated patients (34 of 83) had had a clinical response,as compared with 12 percent of the patients in the placebo group(3 of 25) (P = 0.008). The rates of adverse effects were similarin the groups.
Conclusions A single infusion of cA2 was an effective short-termtreatment in many patients with moderate-to-severe, treatment-resistantCrohn's disease.
Source Information
From the Cedars–Sinai Medical Center, Los Angeles (S.R.T.); the University of Chicago, Chicago (S.B.H.); Academisch Medisch Centrum, Amsterdam (S.J.H.D.); Mt. Sinai Medical Center, New York (L.M., D.H.P.); Centocor, Inc., Malvern, Pa. (T.B., K.L.D., T.F.S.); and Academisch Ziekenhuis Gasthuisberg, Leuven, Belgium (P.J.R.).
Address reprint requests to Dr. Targan at Cedars–Sinai Medical Center, Division of Gastroenterology and Inflammatory Bowel Disease Center D4063, 8700 Beverly Blvd., Los Angeles, CA 90048.
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for Crohn's Disease
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