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 ulcerative 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. Patients 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 Ulcerative Colitis Disease Activity Index score of 0. The Inflammatory Bowel Disease Questionnaire was obtained at each visit. White blood cell concentrations and erythrocyte 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. Response 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 patients had transient leukopenia and one had transient hepatotoxicity.


CONCLUSIONS
Intravenous azathioprine appears to be safe and of clinical benefit in inducing response and avoiding colectomy in severe steroid refractory ulcerative colitis. Data from an i.v. azathioprine trial in Crohn's disease suggests oral dosing alone may obtain the same results. The role of oral dosing alone in severe ulcerative colitis and the role of azathioprine metabolite levels in monitoring efficacy should be investigated further.
Mahadevan
U
U
Division of Gastroenterology and Hepatology, University of California, San Francisco, USA.)
Tremaine
W J
WJ
Johnson
T
T
Pike
M G
MG
Mays
D C
DC
Lipsky
J J
JJ
Sandborn
W J
WJ
D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008780:Methyltransferases / Q000097:blood; D010865:Pilot Projects; D013866:Thioguanine / Q000097:blood
D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine