Mercaptopurine for the treatment of ulcerative colitis - a randomised placebo-controlled trial.

Löwenberg, Mark; Volkers, Adriaan; van Gennep, Sara; Mookhoek, Aart; Montazeri, Nahid; Clasquin, Esmé; Duijvestein, Marjolijn; van Bodegraven, Adriaan; Rietdijk, Svend; Jansen, Jeroen; van Asseldonk, Dirk; van der Zanden, Esmerij; Dijkgraaf, Marcel; West, Rachel; de Boer, Nanne; D'Haens, Geert (2023). Mercaptopurine for the treatment of ulcerative colitis - a randomised placebo-controlled trial. Journal of Crohn's & Colitis, 17(7), pp. 1055-1065. Elsevier 10.1093/ecco-jcc/jjad022

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BACKGROUND AND AIMS

Scepticism about the efficacy of thiopurines for ulcerative colitis (UC) is rising.This study aimed to evaluate mercaptopurine treatment for UC.

METHODS

In this prospective, randomised, double-blind, placebo-controlled trial, patients with active UC, despite treatment with 5-aminosalicylates (5-ASA), were randomised for therapeutic drug monitoring (TDM)-guided mercaptopurine treatment or placebo for 52 weeks. Corticosteroids were given in the first eight weeks and 5-ASA was continued. Proactive metabolite-based mercaptopurine and placebo dose adjustments were applied from week six onwards by unblinded clinicians. The primary endpoint was corticosteroid-free clinical remission and endoscopic improvement (total Mayo score ≤2 points and no item >1) at week 52 in an intention-to-treat analysis.

RESULTS

Between December 2016 and April 2021, 70 patients were screened and 59 were randomised at six centres. In the mercaptopurine group, 16/29 (55.2%) patients completed the 52-week study, compared to 13/30 (43.3%) on placebo. The primary endpoint was achieved by 14/29 (48.3%) patients on mercaptopurine and 3/30 (10%) receiving placebo (Δ=38.3%, 95% CI 17.1-59.4, p=0.002). Adverse events occurred more frequently with mercaptopurine (808.8 per 100 patient years) compared to placebo (501.4 per 100 patient years). Five serious adverse events occurred; four on mercaptopurine and one on placebo. TDM-based dose adjustments were executed in 22/29 (75.9%) patients, leading to lower mercaptopurine doses at week 52 compared to baseline.

CONCLUSIONS

Optimised mercaptopurine treatment was superior to placebo in achieving clinical, endoscopic and histological outcomes at one year following corticosteroid induction treatment in UC patients. More adverse events occurred in the mercaptopurine group.

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