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.

OBJECTIVE

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-naïve 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.