Colon to Rectum

J Crohns Colitis. 2023;17(7):1055–65

Löwenberg M, Volkers A, van Gennep S, Mookhoek A, Montazeri N, Clasquin E, Duijvestein M, van Bodegraven A, Rietdijk S, Jansen J, van Asseldonk D, van der Zanden E, Dijkgraaf M, West R, de Boer N, D’Haens G

Mercaptopurine for the treatment of ulcerative colitis: A randomized placebo-controlled trial


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 end point 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 6 centers. In the mercaptopurine group, 16 of 29 patients (55.2%) completed the 52-week study, compared to 13 of 30 (43.3%) on placebo. The primary end point was achieved by 14 of 29 patients (48.3%) on mercaptopurine and 3 of 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, 4 on mercaptopurine and 1 on placebo. TDM-based dose adjustments were executed in 22 of 29 patients (75.9%), 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 ulcerative colitis patients. More adverse events occurred in the mercaptopurine group.

Dr. Dr. M. Löwenberg, Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands, E-Mail: m.lowenberg@amsterdamumc.nl

DOI: 10.1093/ecco-jcc/jjad022

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