Mercaptopurine for Ulcerative Colitis Helps Achieve Clinical Remission

Thiopurines like mercaptopurine can lead to clinical, endoscopic, and histological outcomes in ulcerative colitis.

Although more adverse events occurred due to treatment with mercaptopurine, almost half of patients with ulcerative colitis (UC) achieved corticosteroid-free clinical, endoscopic, and histological remission after 52 weeks of treatment compared with placebo, according to study findings published in the Journal of Crohn’s & Colitis.

Researchers conducted a 52-week, prospective, multicenter, randomized, double-blind, placebo-controlled trial between December 2016 and April 2021 to determine the efficacy and safety of mercaptopurine in the treatment of patients with UC between the ages of 18 and 80 years.

For 8 weeks, all study participants received induction therapy with 9 mg/day of budesonide or tapered doses of prednisone of 40 mg/day for 2 weeks reduced to 30 mg/day for 1-week followed by weekly dose decreases of 5 mg/day. Budesonide and prednisone were discontinued by week 12; however, all patients continued treatment with 5-aminosalicylates (5-ASA) throughout the duration of the study, unless it was not tolerated well.

Researchers randomly assigned 59 patients with UC to 2 groups: the treatment group that received therapeutic drug monitoring (TDM)-guided mercaptopurine (n=29) and the placebo group (n=30). These treatments were initiated at week 6 with follow-up monitoring with labs, including a complete blood count and metabolic panel as well as TDM occurring at weeks 12, 18, 24, 36, and 52. Fecal calprotectin levels were also measured at weeks 12 and 52.

We believe that our observations can abate skepticism regarding the efficacy of thiopurines for the treatments of UC.

TDM consisted of measuring concentrations of thiopurine metabolites, 6-thioguaninenucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP), within red blood cells. Clinicians altered the dosage of mercaptopurine based on these measurements. They implemented TDM-based mercaptopurine dosage adjustments in 22 of the 29 patients (75.9%) in the intervention group.

Researchers determined efficacy according to achievement of corticosteroid-free clinical remission of UC and improvements on endoscopy as reflected by total Mayo scores of 2 points or less without any item of more than 1 after 52 weeks.

A clinical pathologist analyzed tissues from rectal biopsies that were obtained when no evidence of endoscopic disease activity was observed at week 52. This allowed for histological assessment of disease activity according to the Geboes score, Robarts histopathology index, and Nancy score.

By the end of the study, 14 of the 29 (48.3%) patients with UC in the mercaptopurine treatment group achieved corticosteroid-free clinical, endoscopic, and histological remission compared with 13 of the 30 (10%) patients in the placebo group (change difference=38.3%; 95% CI, 17.1-59.4; P =.002).

Only 16 patients (55.2%) in the treatment group and 13 patients (43.3%) in the placebo group completed the study. Adverse events occurred more commonly in the mercaptopurine group than the placebo group (808.8 per 100 patient-years vs 501.4 per 100 patient-years).

The 4 serious adverse events that occurred in the mercaptopurine group included acute severe colitis, corticosteroid-induced myopathy, and a perianal abscess. Only 1 serious adverse event, a case of acute severe UC, occurred in the placebo group. Clinicians did not consider any of the serious adverse events related to mercaptopurine.

“We believe that our observations can abate skepticism regarding the efficacy of thiopurines for the treatments of UC,” the study authors wrote. “This is not only relevant for the Western world, but also for developing countries, where UC incidence is rising and therapeutic options are often limited.”

Study limitations include failure to reach the calculated sample size, the COVID-19 pandemic’s interference with trial recruitment, problems with blinding, and allowance of 5-ASA dose escalation during disease flares and continued usage in the placebo group due to ethical reasons.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original reference for a full list of authors’ disclosures.


Löwenberg M, Volkers A, van Gennep S, et al. Mercaptopurine for the treatment of ulcerative colitis – a randomised placebo-controlled trial. J Crohns Colitis. Published online February 27, 2023. doi:10.1093/ecco-jcc/jjad022