Short-term efficacy and long-term outcome of cyclosporine treatment in patients with severe ulcerative colitis

Cyclosporine A (CyA) has been recommended for the treatment of severe steroid-resistant ulcerative colitis, however, long-term results are scarce. We prospectively followed a treatment plan in 14 patients with severe ulcerative colitis receiving intravenous CyA after failure to respond to at least eight days of standard therapy 14 with prednisolone (1-1.5 mg/kg/day). CyA was delivered in a daily dose of 5 mg/kg i. v. for a mean of 14 days (range 7-28) in addition to ongoing medical therapy CyA whole blood levels were monitored by HPLC and maintained between 100 ng/ml and 400 ng/ml. Responders were switched to oral CyA (5-7.5 mg/kg/day) for a mean of two months, and steroids were gradually tapered. Eleven patients (79%) initially responded to i. v. CyA, three patients failed to respond and underwent urgent colectomy. Time until response averaged seven days (range 3-13). Four of the eleven responders underwent colectomy because of severe relapse after one, eleven, twelve and 13 months of follow-up. The remaining seven patients were followed for a median of 48 months. During the first year of follow-up three out of seven had a severe relapse and responded to steroids (two patients) or to a further course of i. v. CyA (one patient). During CyA therapy one patient developed staphylococcal sepsis, other adverse events were mild and reversible. The results confirm that CyA is effective in severe steroid-refractory ulcerative colitis. Severe relapse and colectomy are uncommon after the first year of follow-up and the colon preserving effect of CYA can be maintained in up to 50% of patients over a period of four years.