Mercaptopurine for the Treatment of Ulcerative Colitis: A Randomized Placebo-Controlled Trial.

Abstract

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, randomized, double-blind, placebo-controlled trial, patients with active UC, despite treatment with 5-aminosalicylates [5-ASA], were randomized for therapeutic drug monitoring [TDM]-guided mercaptopurine treatment or placebo for 52 weeks. Corticosteroids were given in the first 8 weeks and 5-ASA was continued. Proactive metabolite-based mercaptopurine and placebo dose adjustments were applied from week 6 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 randomized 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% confidence interval [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:

Optimized mercaptopurine treatment was superior to placebo in achieving clinical, endoscopic and histological outcomes at 1 year following corticosteroid induction treatment in UC patients. More adverse events occurred in the mercaptopurine group.

• Authors: Mark Löwenberg, Adriaan Volkers, Sara van Gennep, Aart Mookhoek, Nahid Montazeri, Esmé Clasquin, Marjolijn Duijvestein, Adriaan van Bodegraven, Svend Rietdijk, Jeroen Jansen, Dirk van Asseldonk, Esmerij van der Zanden, Marcel Dijkgraaf, Rachel West, Nanne de Boer, Geert D'Haens
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 17 Issue 7 Pg. 1055-1065 (Jul 05 2023) ISSN: 1876-4479 [Electronic] England
• PMID: 36847130 (Publication Type: Randomized Controlled Trial, Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Mercaptopurine
• Mesalamine

Topics

• Humans
• Colitis, Ulcerative (drug therapy, chemically induced)
• Mercaptopurine (therapeutic use)
• Prospective Studies
• Mesalamine
• Remission Induction