CYCLOSPORINE IN SEVERE ULCERATIVE-COLITIS REFRACTORY TO STEROID-THERAPY

Background. There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced a lmost 40 years ago. In an uncontrolled study, 80 percent of 32 patient s with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy. Methods. We conducted a random ized, double-blind, controlled trial in which cyclosporine (4 mg per k ilogram of body weight per day) or placebo was administered by continu ous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least seven days of intrave nous corticosteroid therapy. A response to therapy was defined as an i mprovement in a numerical symptom score (0 indicated no symptoms, and 21 severe symptoms) leading to discharge from the hospital and treatme nt with oral medications. Failure to respond to therapy resulted in co lectomy, but some patients in the placebo group who had no response an d no urgent need for surgery were subsequently treated with cyclospori ne. Results. Nine of 11 patients (82 percent) treated with cyclosporin e had a response within a mean of seven days, as compared with 0 of 9 patients who received placebo (P<0.001). The mean clinical-activity sc ore fell from 13 to 6 in the cyclosporine group, as compared with a de crease from 14 to 13 in the placebo group. All five patients in the pl acebo group who later received cyclosporine therapy had a response. Co nclusions. Intravenous cyclosporine therapy is rapidly effective for p atients with severe corticosteroid-resistant ulcerative colitis.