TY - JOUR
T1 - Effect of Allopurinol on Clinical Outcomes in Inflammatory Bowel Disease Nonresponders to Azathioprine or 6-Mercaptopurine
AU - Sparrow, Miles P.
AU - Hande, Scott A.
AU - Friedman, Sonia
AU - Cao, Dingcai
AU - Hanauer, Stephen B.
PY - 2007/2
Y1 - 2007/2
N2 - Background & Aims: 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 × 108 red blood cells (P < .001), whereas mean 6-MMP levels decreased from 10,604.7 ± 1278.2 to 2000.6 ± 437.1 pmol/8 × 108 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.
AB - Background & Aims: 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 × 108 red blood cells (P < .001), whereas mean 6-MMP levels decreased from 10,604.7 ± 1278.2 to 2000.6 ± 437.1 pmol/8 × 108 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.
UR - http://www.scopus.com/inward/record.url?scp=33846820178&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2006.11.020
DO - 10.1016/j.cgh.2006.11.020
M3 - Article
C2 - 17296529
AN - SCOPUS:33846820178
SN - 1542-3565
VL - 5
SP - 209
EP - 214
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 2
ER -