Clinical trial: Combination allopurinol-thiopurine versus standard thiopurine in patients with IBD escalating to immunomodulators (the DECIDER study)

Abstract

Background: Thiopurines are established treatments for inflammatory bowel disease (IBD), yet concerns remain regarding their safety.

Aim: To evaluate the use of thiopurine-allopurinol combination therapy compared to standard thiopurine therapy in IBD.

Methods: We performed a multicentre, randomised, placebo-controlled trial to compare the efficacy and safety of thiopurine-allopurinol versus thiopurine with placebo for adults commencing a thiopurine for IBD. Patients had active disease at baseline; dosing of therapy was based on a pre-specified regimen and subsequent metabolites. The primary outcome was the proportion of patients achieving a composite of symptomatic disease activity remission (Harvey Bradshaw Index <5 for Crohn's disease, Simple Clinical Colitis Activity Index <4 for ulcerative colitis) and a faecal calprotectin <150 μg/g after 26 weeks of treatment.

Results: The trial was terminated early due to slow recruitment. We randomised 102 participants (54 thiopurine-allopurinol, 48 thiopurine with placebo) with similar age (median 42 vs 48 years) and sex distribution (46% women per group). A higher proportion achieved the primary outcome in the thiopurine-allopurinol group (50% vs 35%, p = 0.14) and fewer participants stopped their allocated therapy due to adverse events (11% vs 29%, p = 0.02). Also, within the thiopurine-allopurinol group, thiopurine dose adjustments were less frequent (69% vs 92%, p = 0.03), a higher proportion achieved an early therapeutic 6-TGN level at week 6 (71% vs 53%, p = 0.19), and adverse events attributed to therapy were less frequent (15% vs 44%, p = 0.002).

Conclusion: Thiopurine-allopurinol therapy is safe and mitigates thiopurine adverse effects, thus enhancing tolerability without compromising efficacy (ACTRN12613001347752).