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DRUG INFORMATION ROUNDS

Cyclosporine for Severe Ulcerative Colitis

at time of writing, Clinical and Research Fellow, University of Michigan College of Pharmacy, Ann Arbor, MI; now, Clinical Assistant Professor, University of Montréal Faculty of Pharmacy; Clinical Pharmacy Specialist, McGill University Health Centre, Montréal General Hospital, Montréal, Québec, Canada

Carly B Efros, PharmD

at time of writing, PharmD Student, University of Michigan College of Pharmacy

Rosemary R Berardi, PharmD FCCP FASHP FAPHA

Professor of Pharmacy, University of Michigan College of Pharmacy; Clinical Pharmacy Specialist, Gastrointestinal and Liver Diseases, Department of Pharmacy, University of Michigan Health-System, Ann Arbor

Reprints: Dr. Berardi, University of Michigan College of Pharmacy, 428 Church St., Ann Arbor, MI 48109-1065, fax 734/763-4480, rberardi{at}umich.edu

OBJECTIVE: To evaluate evidence for the use of cyclosporine in treating patients with severe ulcerative colitis.

DATA SOURCES: A literature search was performed using MEDLINE, EMBASE, Cochrane Database, and ISI Web of Knowledge (1966-November 2005) with the search terms cyclosporine, cyclosporin A, CsA, ulcerative colitis, UC, inflammatory bowel disease, IBD, steroid-refractory, and immunosuppression. Additional papers were located by hand-searching relevant references. Only human studies in adults and literature published in English were included.

DATA SYNTHESIS: Intravenous cyclosporine has been evaluated for the treatment of severe ulcerative colitis in 4 randomized, controlled trials, as well as in many open-label and retrospective studies. Studies that evaluated cyclosporine for severe ulcerative colitis were reviewed. All 4 controlled trials showed an initial positive clinical response as defined by the Crohn's Activity Index when intravenous cyclosporine 4 mg/kg/day was administered as monotherapy or combined with intravenous corticosteroids. One of the 4 trials indicated that high-dose cyclosporine (4 mg/kg/day) has no additional clinical benefit over the low-dose (2 mg/kg/day) and that the lower dose may improve safety related to dose-dependent adverse effects.

CONCLUSIONS: There is evidence to support the use of intravenous cyclosporine for patients with severe ulcerative colitis who are refractory to corticosteroid therapy. Because most of the adverse effects associated with cyclosporine are dose dependent, therapy should be initiated with the lower 2 mg/kg/day dose. Subsequent doses should be adjusted based on cyclosporine blood concentrations of 150-250 ng/mL. Cyclosporine should be used only to induce remission and serve as a "bridge" to azathioprine or 6-mercaptopurine maintenance therapy. At this time, there are insufficient data to support the long-term use of cyclosporine monotherapy for avoidance of surgery or maintenance of remission.

Key Words: azathioprine, colectomy, corticosteroid-refractory, cyclosporine, inflammatory bowel disease, ulcerative colitis

Published Online, December 20, 2005. www.theannals.com, DOI 10.1345/aph.1G374