Treatment withdrawal with near-normal histology in UC tied to clinical relapse

A normal or near-normal histology in ulcerative colitis (UC) is associated with moderate rates of clinical relapse, suggests a study.

“Physicians should be cautious when considering withdrawing inflammatory bowel disease (IBD) therapy as this was associated with an increased risk of clinical relapse,” the investigators said.

A retrospective single-centre study was conducted in patients with UC who were in endoscopic remission with normal histology. A gastrointestinal expert pathologist reread the pathology slides and scored both the right and left colon using the Geboes score. Time to clinical relapse was the primary outcome, while episodes of dysplasia and colectomy were secondary.

Of the 78 UC patients who had normal histology reported, only two were found to have a completely normal histology on expert review. [J Clin Gastroenterol 2025;59:1018-1023]

Clinical relapse occurred at a mean of 4.7 years in approximately one-fifth of participants. Neither right- nor left-sided colon histology predicted the occurrence of future clinical relapse. Notably, 43 percent of patients who stopped IBD therapy had a clinical relapse and showed a greater chance of relapse than those who did not withdraw therapy (hazard ratio, 4.89, 95 percent confidence interval, 1.32‒18.08).

No episodes of dysplasia were reported during follow-up. Furthermore, two participants who had a relapse ended up receiving a colectomy.

“We found that histologic near-normalization, as defined by Geboes score, is associated with no risk for dysplasia over a mean of 7.3 years. Hence, surveillance colonoscopy intervals can be lengthened in persons with such histology,” the investigators said.

“Even when a person with UC achieves normal or near-normal histology, physicians should be cautious when considering withdrawing their therapy,” they added.

Withdrawal

Recently, treatment withdrawal has been gaining momentum as a means to reduce the long-terms risks of immunomodulators or advanced therapies, including increased risk of infection and malignancies. [Clin Gastroenterol Hepatol 2020;18:69-81e3; Inflamm Bowel Dis 2023;29:1047-1056; JAMA 2017;318:1679-1686]

For instance, a study by Cassinotti and colleagues on azathioprine withdrawal in UC patients showed that half of the participants had a relapse at 2 years and two-thirds by 5 years. However, the only criteria used for inclusion was steroid-free clinical remission. [Am J Gastroenterol 2009;104:2760-2767]

A systematic review by Torres and colleagues reported relapse rates involving immunomodulator withdrawal ranging from 11 percent to 77 percent at 1 year and 21 percent to 100 percent at 2 years. The data used to assess the risk in withdrawing biological or novel oral small molecules mostly involved anti-TNF therapies. [Gastroenterology 2015;149:1716-1730]

Discontinuation of anti-TNF therapy in UC patients had a cumulative risk of relapse ranging from 35 percent to 45 percent, with median follow-up of 16‒29 months. [Gastroenterology 2015;149:1716-1730]

Moreover, another study assessing clinical relapse rates in persons with UC in steroid-free remission who withdrew off infliximab found that only 40 percent remained in remission at 4.5 years. [Scand J Gastroenterol 2012;47:518-527]

“Our study also revealed higher relapse rates in those who withdrew off therapy, with a slightly longer time to relapse rate of 4.2 years,” the researchers said.