A SHORT-TERM STUDY OF CHIMERIC MONOCLONAL-ANTIBODY CA2 TO TUMOR-NECROSIS-FACTOR-ALPHA FOR CROHNS-DISEASE

Background Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor alpha, specifically chim eric monoclonal antibody cA2, in the treatment of Crohn's disease. Met hods We conducted a 12-week multicenter, double-blind, placebo-control led trial of cA2 in 108 patients with moderate-to-severe Crohn's disea se that was resistant to treatment. All had scores on the Crohn's Dise ase Activity Index between 220 and 400 (scores can range from 0 to abo ut 600, with higher scores indicating more severe illness). Patients w ere randomly assigned to receive a single two-hour intravenous infusio n of either placebo or cA2 in a dose of 5 mg per kilogram of body weig ht, 10 mg per kilogram, or 20 mg per kilogram. Clinical response, the primary end point, was defined as a reduction of 70 or more points in the score on the Crohn's Disease Activity Index at four weeks that was not accompanied by a change in any concomitant medications. Results A t four weeks, 81 percent of the patients given 5 mg of cA2 per kilogra m (22 of 27 patients), 50 percent of those given 10 mg of cA2 per kilo gram (14 of 28), and 64 percent of those given 20 mg of cA2 per kilogr am (18 of 28) had had a clinical response, as compared with 17 percent of patients in the placebo group (4 of 24) (P<0.001 for the compariso n of the cA2 group as a whole with placebo). Thirty-three percent of t he patients given cA2 went into remission (defined as a score below 15 0 on the Crohn's Disease Activity Index), as compared with 4 percent o f the patients given placebo (P=0.005). At 12 weeks, 41 percent of the cA2-treated patients (34 of 83) had had a clinical response, as compa red with 12 percent of the patients in the placebo group (3 of 25) (P= 0.008). The rates of adverse effects were similar in the groups. Concl usions A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe, treatment-resistant Crohn's disease. (C) 1997, Massachusetts Medical Society.