Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis.
OBJECTIVE
Cyclosporine A is highly effective in severe attacks of ulcerative colitis (UC) but is associated with important adverse effects that are mainly dose dependent. Our single center, randomized, double-blind, controlled trial aimed to evaluate the additional clinical benefit of 4 mg/kg over 2 mg/kg IV cyclosporine in the acute treatment of severe UC.


METHODS
Primary end point was the proportion of patients with a clinical response. Secondary end points included time to response, colectomy rate, and adverse effects.


RESULTS
Seventy-three patients were included. Day-8 response rates were 84.2% (32 of 38, 4 mg/kg) and 85.7% (32 of 35, 2 mg/kg) after a median of 4 days in both groups. Short-term colectomy rates were 13.1% (4 mg/kg) and 8.6% (2 mg/kg). Mean cyclosporine blood levels were 237 +/- 33 in the 2-mg/kg group and 332 +/- 43 ng/mL in the 4-mg/kg group. Active smoking was inversely correlated with clinical response (odds ratio, 0.06), but concomitant azathioprine or steroids were not predictive. A trend toward a higher incidence of hypertension was observed in the 4-mg/kg group (23.7% vs. 8.6%, 2 mg/kg, P < 0.08).


CONCLUSIONS
High-dose IV cyclosporine has no additional clinical benefit over low dose in the treatment of severe UC. Although we did not observe differences in adverse effects on the short term, the use of 2 mg/kg IV cyclosporine should provide an improved toxicity profile for medical treatment of severe UC.
D000208:Acute Disease; D000328:Adult; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy*; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004311:Double-Blind Method; D016145:Endoscopy, Digestive System; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine