Complete Endoscopic Healing in IBD Linked to Lower Relapse Risk

Patients with inflammatory bowel disease (IBD) have a high risk of relapse after stopping tumor necrosis factor (TNF) inhibitors, but those who achieved complete endoscopic healing had a far lower risk, according to a prospective study from the Netherlands.

Among 81 patients, 70% of those who achieved partial endoscopic healing relapsed at 1 year, as compared with 35% of those who achieved complete endoscopic healing (adjusted HR 3.28, 95% CI 1.43-7.50), reported Bas Oldenburg, MD, PhD, of the University Medical Center Utrecht, and colleagues.

Moreover, for patients with ulcerative colitis or unclassified IBD, the use of mesalamine was linked to fewer relapses (aHR 0.08, 95% CI 0.01-0.67), they noted in Clinical Gastroenterology and Hepatology.

“Risk of relapse was lower among patients with complete endoscopic healing, compared with partial endoscopic healing,” Oldenburg and team concluded. “This large difference underscores the clinical importance of this finding.”

Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute at the Cleveland Clinic in Ohio, noted that “despite these encouraging results, I would not suggest stopping therapy in a patient in remission.”

“We have not yet found a cure for IBD and it is improbable to think that a lifelong remission would be achieved off of therapy,” Regueiro told MedPage Today. “Additionally, there are patients who may have a more severe disease relapse after stopping therapy.”

“Still, the concept of withdrawing therapy in IBD patients in deep remission is appealing,” he added.

IBD patients in clinical remission who discontinue TNF inhibitors may experience fewer adverse events, but remain at high risk for relapse, for which endoscopic activity at the time of discontinuation may play a role, Oldenburg’s group noted. Although those who achieve endoscopic healing may be at lower risk for relapse, the degree of endoscopic healing that needs to be achieved prior to de-escalating treatment is not well understood.

Of note, time between baseline endoscopy and TNF inhibitor discontinuation — less than 6 months for 95% of patients — was not a predictor for the risk of relapse. In addition, for those with complete endoscopic healing, subtherapeutic anti-TNF trough levels or the use of immunomodulators were not predictors for relapse risk.

For this study, Oldenburg and colleagues examined data on 81 patients with IBD across 13 hospitals in the Netherlands from 2018 to 2020. Of these patients, 41 had Crohn’s disease and 40 had ulcerative colitis or unclassified IBD. Participants were in corticosteroid-free clinical remission and endoscopic remission for at least 6 months, and electively discontinued maintenance TNF inhibitors.

Median age was 40, and 52% were women. The average age at diagnosis was 28.5; average disease duration was 9 years, and duration of remission was 3.5 years. Nearly three-quarters of patients had received infliximab (Remicade).

Overall, 88% had complete endoscopic healing, which was defined by a Mayo score of 0 and a Simple Endoscopic Score for Crohn’s disease (SES-CD) of 0-2 without any large ulcers, while 12% had partial endoscopic healing, defined by a Mayo score of 1 and an SES-CD score of 3-4.

Of the 81 patients, 40 relapsed over a median follow-up of 2 years, with comparable rates among patients with Crohn’s disease, ulcerative colitis, and unclassified IBD, and between TNF inhibitors– infliximab or adalimumab (Humira).

After stopping TNF inhibitors, 20% were taking mesalamine. At relapse, the preferred strategy was to reintroduce TNF inhibitors, with most restarting the same agent (87%).

Of the 30 patients who restarted TNF inhibitors, clinical remission was regained in 73% at 3 months.

“Furthermore, patient-reported quality of life and general well-being declined at the time of relapse, but was restored with reintroduction of treatment. As a result, quality of life and general well-being were similar between patients who relapsed versus those who maintained remission, when considering the entire follow-up on a population level,” Oldenburg and colleagues wrote.

Three patients were hospitalized for IBD, and one with Crohn’s disease required ileocecal resection for symptomatic stenosis.

Oldenburg and team acknowledged that the number of patients with partial endoscopic healing in their study was small, “resulting in wide confidence intervals for this parameter.” Furthermore, the findings may not be generalizable to those with more severe IBD phenotypes, since only a few with stricturing or penetrating Crohn’s disease were included.