LOW-DOSE CYCLOSPORINE FOR THE TREATMENT OF CROHNS-DISEASE

Background. Long-term corticosteroid therapy for Crohn's disease is as sociated with important types of morbidity, such as osteoporosis. Safe and effective alternative treatments are required. Although a short-t erm benefit of cyclosporine in active Crohn's disease has been suggest ed, the long-term safety and efficacy of this treatment have not been established. Methods. We conducted a randomized, double-blind, placebo -controlled evaluation of the effect of 18 months of low-dose cyclospo rine treatment on the course of Crohn's disease. Adult patients whose disease had been active within the previous two years were randomly as signed to receive cyclosporine (151 patients) or placebo (154 patients ) in addition to their usual therapy. Randomization was stratified acc ording to center and score on the Crohn's Disease Activity Index (193 patients had scores of 150 or less, and 112 had scores greater than 15 0). The primary outcome measure was clinically important worsening of Crohn's disease, defined as a 100-point increase in the Crohn's Diseas e Activity Index from the patient's base-line value. Secondary outcome s were the use of prednisone and 5-aminosalicylates, mean score on the Crohn's Disease Activity Index and mean quality-of-life score, and th e need for surgery. Results. The condition of more patients worsened w ith cyclosporine than with placebo (91 of 151, or 60.3 percent, vs. 80 of 154, or 51.9 percent; P = 0.10). The median time to worsening of d isease in patients receiving cyclosporine was 338 days, as compared wi th 492 days in patients receiving placebo (P = 0.25; relative risk, 1. 22; 95 percent confidence interval, 0.86 to 1.72). Analyses of the mea n Crohn's Disease Activity Index and quality-of-life scores and of the use of prednisone and 5-aminosalicylates also failed to demonstrate b enefit. Conclusions. In our patient population, the addition of low-do se cyclosporine to conventional treatment for Crohn's disease did not improve symptoms or reduce requirements for other forms of therapy.