Randomized clinical trial: a pilot study comparing efficacy of low-dose azathioprine and allopurinol to azathioprine on clinical outcomes in inflammatory bowel disease.

Background: Treating inflammatory bowel diseases (IBD) using thiopurines is effective; however, a high rate of adverse effects and lack of efficacy limit its use. Retrospective studies have suggested that treatment with low-dose thiopurines in combination with allopurinol is associated with higher remission rates and lower incidence of adverse events.Aim: To compare the rates of clinical remission and the rates of adverse events in IBD patients treated with either standard treatment with azathioprine or low-dose azathioprine in combination with allopurinol.Methods: A prospective, open-label study, randomizing thiopurine-naive IBD patients with normal thiopurine methyltransferase to 24 weeks of treatment with either standard azathioprine dose or low-dose azathioprine and allopurinol.Results: A total of 46 patients with ulcerative colitis or Crohn's disease were randomized. We conducted an intention to treat analysis and found a significant (69.6%) proportion of the patients treated with low-dose azathioprine in combination with allopurinol was in clinical remission without the need for steroid or biologic treatment at week 24 compared to 34.7% of the patients treated with azathioprine monotherapy (RR, 2.10 [95% CI: 1.07-4.11]). In the azathioprine group, 47.8% of the patients compared to 30.4% of the patients in the azathioprine-allopurinol group had to withdraw from the study due to adverse events (RR, 1.47 [95% CI: 0.76-2.85])Conclusions: This study indicated that by changing the treatment strategy from standard weight-based dosing of azathioprine to weight-based low-dose azathioprine in combination with allopurinol, we can increase remission rates in patients with IBD.