Colon to Rectum
J Crohns Colitis. 2023;17(7):1055–65
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.