Effect of allopurinol on clinical outcomes in inflammatory bowel disease nonresponders to azathioprine or 6-mercaptopurine.
OBJECTIVE
Many IBD patients not responding to azathioprine (AZA) or 6-mercaptopurine (6-MP) preferentially metabolize 6-MP to 6-methylmercaptopurine (6-MMP). We describe the use of allopurinol in AZA/6-MP nonresponders to deliberately shunt metabolism of 6-MP toward 6-thioguanine (6-TGN) and improve clinical responses.


METHODS
Twenty outpatients who were AZA/6-MP nonresponders and had high 6-MMP metabolite levels were included. Subjects were commenced on allopurinol 100 mg daily, and the dose of 6-MP/AZA was reduced to 25%-50% of the original dose.


RESULTS
After allopurinol was started, mean 6-TGN levels increased from 191.3 (+/- standard error of the mean) +/- 17.1 to 400.3 +/- 36.9 pmol/8 x 10(8) red blood cells (P < .001), whereas mean 6-MMP levels decreased from 10,604.7 +/- 1278.2 to 2000.6 +/- 437.1 pmol/8 x 10(8) red blood cells (P < .001). The addition of allopurinol led to a reduction in the mean partial Harvey Bradshaw Index in Crohn's disease patients from 4.9 +/- 1.0 to 1.5 +/- 0.3 points (P = .001), and in ulcerative colitis patients mean Mayo Scores decreased from 4.1 +/- 0.7 to 2.9 +/- 0.7 points (P = .13). The addition of allopurinol enabled a reduction in mean daily prednisone dosage from 17.6 +/- 3.9 to 1.8 +/- 0.7 mg (P < .001) and led to normalization of transaminase levels, with mean AST levels reducing from 42.5 +/- 8.1 to 23.5 +/- 1.6 IU (P = .12) and mean ALT levels reducing from 101.6 +/- 26.9 to 33.9 +/- 5.2 IU (P = .01).


CONCLUSIONS
The addition of allopurinol to thiopurine nonresponders with high 6-MMP metabolite levels is an effective and safe means of optimizing 6-TGN production, leading to improved disease activity scores, reduced corticosteroid requirements, and normalization of liver enzymes.
Sparrow
Miles P
MP
Section of Gastroenterology and Nutrition, University of Chicago Medical Center, Chicago, Illinois, USA. miles.sparrow@med.monash.edu.au
Hande
Scott A
SA
Friedman
Sonia
S
Cao
Dingcai
D
Hanauer
Stephen B
SB
D000493:Allopurinol / Q000378:metabolism / Q000627:therapeutic use*; D001379:Azathioprine / Q000378:metabolism / Q000627:therapeutic use*; D004357:Drug Synergism; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D015122:Mercaptopurine / Q000378:metabolism / Q000627:therapeutic use*; D013866:Thioguanine / Q000378:metabolism; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D000493:Allopurinol; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine