Intravenous azathioprine in severe ulcerative colitis: A pilot study

OBJECTIVE: Azathioprine use in acute ulcerative colitis has been limited by its perceived long onset of action. The aim of this study was to determine the safety and clinical effect of an i.v. loading dose of azathioprine in the setting of severe steroid refractory ulcerative colitis. METHODS: Nine hospitalized patients with severe steroid refractory ulcerati ve colitis were enrolled. Patients 1-3 received 20 mg/kg i.v. azathioprine over 36 h. Patients 4-6 received 40 mg/kg i.v. azathioprine over 36 h. Pati ents 7-9 received 40 mg/kg i.v. azathioprine as three 8-h infusions over 3 days. Clinical remission was defined as steroid withdrawal and an Ulcerativ e Colitis Disease Activity Index score of 0. The Inflammatory Bowel Disease Questionnaire was obtained at each visit. White blood cell concentrations and erthyrocyte concentrations of 6-thioguanine were obtained. RESULTS: Five of nine patients (56%) had a response and avoided colectomy. Three of nine patients (33%) met the definition for clinical remission. Res ponse was seen within 4 wk. The mean 6-thioguanine concentration for those five patients at 12 wk after infusion was 148.2 pmol/8 X 10(8). Two patient s had transient leukopenia and one had transient hepatotoxicity. CONCLUSIONS: Intravenous azathioprine appears to be safe and of clinical be nefit in inducing response and avoiding colectomy in severe steroid refract ory ulcerative colitis. Data from an i.v. azathioprine trial in Crohn's dis ease suggests oral dosing alone may obtain the same results. The role of or al dosing alone in severe ulcerative colitis and the role of azathioprine m etabolite levels in monitoring efficacy should be investigated further. (C) 2000 by Am. Cell. of Gastroenterology.