A Placebo-Controlled, Double-Blind, Randomized Trial of Cyclosporine Therapy in Active Chronic Crohn's Disease

We randomly assigned 71 patients with active chronic Crohn's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohn's Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) In the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn's disease and resistance to or intolerance of corticosteroids. (N Engl J Med 1989; 321:845–50.) CROHN'S disease is a chronic inflammatory bowel disease of unknown origin and pathogenesis. The failure to demonstrate a causal infectious agent and the proved efficacy of corticosteroids 1 , 2 and immunosuppressive agents such as 6-mercaptopurine 3 suggest it is an immunologic disorder. Epidemiologic studies generally indicate that Crohn's disease is relatively mild in about 75 percent of patients. In a minority, however, it has a severe course, in which disease activity continues despite intensive treatment. 4 For patients who are resistant to corticosteroids, sulfasalazine, and metronidazole or who cannot tolerate these drugs, no medical treatment other than immunosuppressive therapy is available. Cyclosporine is a . . .