Combination of thiopurines and allopurinol: adverse events and clinical benefit in IBD.
OBJECTIVE
Allopurinol has been presented as a safe and effective adjunct to thiopurine therapy in inflammatory bowel disease (IBD). We aimed to determine the rate of infectious complications and clinical successes with a combination of thiopurine/allopurinol in IBD, and to identify which variables predict 6-thioguanine, 6-methylmercaptopurine, and white blood cell levels. Additionally we aimed to identify which variables predict complications.


METHODS
A retrospective database search identified patients with inflammatory bowel disease on both thiopurines and allopurinol. Regression modeling was used to identify which variables predicted metabolite levels, white blood cell levels, and complications.


RESULTS
Twenty-seven subjects were found, with 20 treated intentionally and 7 inadvertently after a concurrent gout diagnosis. Thirteen of 20 patients had a major clinical improvement and 7 of 16 stopped steroids. Five infectious complications occurred. These included 2 cases of shingles, and one each of PCP, EBV, and viral meningitis. Significant predictors of metabolite levels included the dose of thiopurine and allopurinol, age, and BMI. Low white blood cell count levels were associated with increased doses, high BMI, and older age. Despite having only 5 events, there was a difference in absolute lymphocyte count between patients with and without infection (median 200 per mm³ vs 850 per mm³ respectively, p=0.0503).


CONCLUSIONS
Adjunctive allopurinol therapy in shunting patients produced major clinical improvement in 48% of patients. However, a surprising number of opportunistic infections have occurred. Low absolute lymphocyte count may be a previously unrecognized indicator of risk of opportunistic infections.
University of Michigan, Department of Internal Medicine, Division of General Medicine, United States.
Shail M
SM
Govani
Peter D R
PD
Higgins
D000328:Adult; D000493:Allopurinol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy; D003424:Crohn Disease / Q000188:drug therapy; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D008875:Middle Aged; D009894:Opportunistic Infections / Q000139:chemically induced; D012189:Retrospective Studies; D055815:Young Adult
D007166:Immunosuppressive Agents; D000493:Allopurinol; D015122:Mercaptopurine; D001379:Azathioprine