Sa1917 Efficacy of Allopurinol Added to 6MP or Azathioprine for Inflammatory Bowel Disease

Abstract

INTRODUCTION Azathioprine (AZA) and 6-mercaptopurine (6MP) are indicated for the induction and maintenance of remission in patients with IBD. A drawback is their narrow therapeutic window. Therapeutic levels of the metabolite 6-thioguanine (6TGN) are associated with clinical remission. Adverse effects of 6-methylmercaptopurine ribonucleotide (6MMPN) include hepatotoxicity. Patients who selectively metabolize 6MP to 6MMPN can be identified and co-treated with allopurinol (allo), which shifts metabolism to 6TGN. The use of these measurements remains controversial as some experts maintain that outcomes are unchanged from standard therapy. We retrospectively reviewed charts of patients with toxic levels of 6MMPN who were treated with allo to determine if goals of therapy were achieved. METHODS A list of all patients who had 6MP/AZA metabolites measured in the last 4 years was obtained from Prometheus laboratory. The list included 32 patients, 14 met our criteria. Data was collected regarding age, sex, diagnosis, ESR, CRP, 6MMPN and 6TGN levels and need for anti-TNF therapy before and after initiation of allo, subjective improvement of patient's symptoms. RESULTS 14 patients were treated with allo due to toxic levels of 6MMPN (mean 11175 pmol/8X10^8RBC range 5936-22398). The average age was 49 yrs (range 22-90). 7(50%) were men. 8(57%) had Crohn's, 5(35%) had UC, and 1(7.1%) had indeterminate colitis. Following initiation of allo, all patients had normalization of 6MMPN levels (mean 996.5 range 979-1014). 4(25%) patients had therapeutic 6TGN levels prior to initiating allo. Following allo, 11(79%) reached therapeutic 6TGN levels, 1 achieved near therapeutic level (223) and 2 did not have follow up data. The average levels before and after therapy with allo was 191(range 117-355) and 330.1 pmol/8X10^8RBC (range 223-498), respectively. The average ESR before and after the initiation of allo was 24.7(range 1-111) and 18.7(range 1-76), respectively with an average decrease of 6 mm/ hr. 50% of the patients had a greater than 30% decrease in ESR. The average CRP before and after allo was 3.2 mg/L (range 0.1-18.6) and 0.56(range 0.1-2.4), respectively with an average decrease of 2.66. 57% of the patients had a greater than 40% decrease in CRP. 12 (86%) reported improvement in global symptoms following initiation of allo. 2 of the 3 patients who were on anti-TNF therapy prior to initiation of allo were able to discontinue it, 1 patient had to be switched to biologics due to pancytopenia and 1 required biologics due to lack of response to 6MP/allo . CONCLUSION Our study shows that initiation of allo in patients with elevated 6MMPN level results in normalization of 6MMPN level, achieves therapeutic levels of 6TGN, improvement of subjective symptoms, lab parameters used to assess inflammatory activity(ESR, CRP) and decrease in need for anti-TNF therapy.