Long term efficacy and safety of allopurinol and azathioprine or 6-mercaptopurine in patients with inflammatory bowel disease

Background and aims: We previously reported that IBD patients who are non-responders to thiopurines with preferential shunting of metabolites to hepatotoxic 6-methylmercaptopurine ribonucleotides compared to 6-thioguanine nucleotides can reverse the ratio of 6-MMP/6-TGN and respond to thiopurines with the addition of allopurinol. The objective of this study is to report long term efficacy and safety, along with results for an additional 11 patients. Methods: Retrospective chart review of patients at the University of Chicago IBD Center treated with allopurinol in addition to thiopurines. Results: Twenty five patients with Crohn's disease or ulcerative colitis were enrolled. Within the first month of therapy 6-TGN metabolite levels increased from a mean of 186.5 ± 17.4 (SE) to 352.8 ± 37.8 pmol/8 × 10⁸ (p = 0.0001). Over the same period 6-MMP levels decreased from a mean of 11,966 ± 1697 to 2004 ± 536 pmol/8 × 10⁸ (p < 0.0001). The mean daily dosage of prednisone decreased from 19.8 ± 3.8 mg to 5.3 ± 2.7 mg (p = 0.03). Thirteen patients have a minimum of one year follow-up. Nine of these thirteen patients have continued on therapy for at least 2 years. All thirteen of these patients continue to be in clinical remission at the last follow-up visit. No patients have had evidence of sustained thrombocytopenia or abnormal liver enzymes. Conclusions: In AZA/6-MP non-responders with increased 6-MMP/6-TGN ratios, addition of allopurinol continues to demonstrate safety and efficacy for long-term maintenance and steroid-sparing in IBD.