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- W2793469548 abstract "Summary Background Thiopurine hypermethylation towards 6‐methylmercaptopurine (6 MMP ) instead of 6‐thioguanine nucleotides (6 TGN ) is associated with inefficacy in patients with IBD. Allopurinol reverses such hypermethylation. Aims To prospectively determine efficacy of allopurinol‐thiopurine combination and to compare 2 doses of allopurinol. Design In a multicentre, double‐blind trial, patients with clinically active or steroid‐dependent IBD and thiopurine shunting were randomised to 50 or 100 mg/d allopurinol and 25% of their screening thiopurine dose, which was subsequently optimised, aiming for 6 TGN of 260‐500 pmol/8x10 8 RBC s. The primary endpoint was steroid‐free clinical remission at 24 weeks. Results Of 73 patients, 39 (53% [95% CI 42‐65]) achieved steroid‐free remission, (54% with 50 mg/d and 53% with 100 mg/d). 81% were able to discontinue steroids. Therapeutic 6 TGN levels were achieved in both groups. Final thiopurine doses were lower with 100 mg/d allopurinol ( P < 0.005). 6 MMP : 6 TGN ratio decreased from mean 64 to 4 ( P < 0.001), being higher with 50 mg/d (6 ± 1.83) than for 100 mg/d ([1 ± 0.16], P = 0.003). Three patients on 50 mg/d failed to sustain low ratios at 24 weeks. Toxicity was minimal; three patients on 50 mg/d allopurinol developed transient leukopenia. Alanine aminotransferase concentrations decreased ( P < 0.001) similarly in both arms. Faecal calprotectin levels at study end were lower in patients who achieved the primary endpoint (median 171 [85‐541] vs 821[110‐5892] ug/g, P = 0.03). Conclusions Low‐dose allopurinol‐thiopurine combination safely reverses shunting and optimises 6 TGN with associated improvement in disease activity. 100 mg/d allopurinol is preferable due to greater metabolite profile stability and lower thiopurine dose without additional toxicity." @default.
- W2793469548 created "2018-03-29" @default.
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- W2793469548 date "2018-02-21" @default.
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- W2793469548 title "Randomised clinical trial: efficacy, safety and dosage of adjunctive allopurinol in azathioprine/mercaptopurine nonresponders (<scp>AAA</scp> Study)" @default.
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- W2793469548 doi "https://doi.org/10.1111/apt.14571" @default.
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