TY - JOUR
T1 - Mercaptopurine for the Treatment of Ulcerative Colitis
T2 - A Randomized Placebo-Controlled Trial
AU - Löwenberg, Mark
AU - Volkers, Adriaan
AU - van Gennep, Sara
AU - Mookhoek, Aart
AU - Montazeri, Nahid
AU - Clasquin, Esmé
AU - Duijvestein, Marjolijn
AU - van Bodegraven, Adriaan
AU - Rietdijk, Svend
AU - Jansen, Jeroen
AU - van Asseldonk, Dirk
AU - van der Zanden, Esmerij
AU - Dijkgraaf, Marcel
AU - West, Rachel
AU - de Boer, Nanne
AU - D'Haens, Geert
N1 - Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. All rights reserved.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - 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.
AB - 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.
KW - Ulcerative colitis
KW - immunomodulators
KW - randomized controlled trial
KW - therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=85164237975&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/ecco-jcc/jjad022
DO - https://doi.org/10.1093/ecco-jcc/jjad022
M3 - Article
C2 - 36847130
SN - 1873-9946
VL - 17
SP - 1055
EP - 1065
JO - Journal of Crohn's and Colitis
JF - Journal of Crohn's and Colitis
IS - 7
ER -