{Reference Type}: Randomized Controlled Trial
{Title}: Mercaptopurine for the Treatment of Ulcerative Colitis: A Randomized Placebo-Controlled Trial.
{Author}: 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;
{Journal}: J Crohns Colitis
{Volume}: 17
{Issue}: 7
{Year}: Jul 2023 5
{Factor}: 10.02
{DOI}: 10.1093/ecco-jcc/jjad022
{Abstract}: <B>OBJECTIVE: </B>Scepticism about the efficacy of thiopurines for ulcerative colitis [UC] is rising. This study aimed to evaluate mercaptopurine treatment for UC.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.