A Research Team Led by Professor Byong Duk Ye of Asan Medical Center and Professor Jeongkuk Seo of Chung-Ang University Hospital Analyzes 6,235 Patients with Inflammatory Bowel Disease in a Nationwide Study

Discontinuing Immunomodulators Does Not Increase Recurrence Risk in Crohn's Disease, Highlighting the Need for Disease Specific Treatment Strategies

▲ (From left) Professor Byong Duk Ye of the Division of Gastroenterology at Asan Medical Center and Professor Jeongkuk Seo of the Division of Gastroenterology at Chung-Ang University Hospital.

Inflammatory bowel disease (IBD), primarily represented by Crohn's disease and ulcerative colitis, is a chronic condition that requires lifelong treatment. For patients with moderate to severe disease, the standard treatment is combination therapy using an anti-tumor necrosis factor (anti TNF) agent, an injectable biologic that selectively suppresses inflammatory mediators, together with an immunomodulator.

However, long-term use of immunomodulators has been associated with an increased risk of adverse effects, including lymphoma, highlighting the need for evidence on whether immunomodulators can be safely discontinued while maintaining anti TNF therapy.

A recent study found that discontinuing immunomodulators during anti TNF therapy did not increase the risk of disease relapse in patients with Crohn's disease. In contrast, patients with ulcerative colitis experienced a higher risk of relapse after discontinuing immunomodulators. The findings highlight the need for disease specific treatment strategies, even within the same category of inflammatory bowel disease.

A research team led by Professor Byong Duk Ye of the Division of Gastroenterology at Asan Medical Center and Professor Jeongkuk Seo of the Division of Gastroenterology at Chung-Ang University Hospital reported that patients with ulcerative colitis receiving anti TNF therapy may face a 20% higher risk of disease worsening if they discontinue thiopurines, commonly used immunomodulators.

Combination therapy with an anti TNF agent and an oral immunomodulator is currently the standard treatment for patients with moderate to severe inflammatory bowel disease. Compared with anti TNF monotherapy, this approach offers higher rates of mucosal healing and helps maintain long-term treatment efficacy by reducing the formation of anti-drug antibodies.

However, prolonged use of immunomodulators has been associated with an increased risk of lymphoma, other malignancies, and infections. East Asian patients are also known to have a relatively higher risk of bone marrow suppression, including leukopenia, because of genetic susceptibility.

▲ Professor Byong Duk Ye of the Division of Gastroenterology at Asan Medical Center explains inflammatory bowel disease to a patient.

To address this question, the research team analyzed data from the Health Insurance Review and Assessment Service covering the period from 2007 to 2020 to evaluate the real world impact of discontinuing immunomodulators after initiating anti TNF therapy.

The study included 6,235 patients with inflammatory bowel disease who had been receiving immunomodulators and initiated anti TNF therapy between 2008 and 2019. Patients were divided into two groups based on whether they discontinued or continued immunomodulator therapy. The researchers then compared the risk of disease worsening, including the need for new corticosteroid treatment, inflammatory bowel disease related hospitalization, and bowel surgery.

Among patients with ulcerative colitis, those who discontinued immunomodulators had a 20% higher risk of disease worsening than those who continued treatment. They also had an 18% higher risk of requiring corticosteroids to control disease activity.

In contrast, no significant association was observed between immunomodulator discontinuation and the risk of disease worsening in patients with Crohn's disease. Although both conditions are classified as inflammatory bowel disease, the impact of discontinuing immunomodulators differed between patients with ulcerative colitis and those with Crohn's disease.

Co first author Professor Jeongkuk Seo of the Division of Gastroenterology at Chung-Ang University Hospital said, "This study is particularly meaningful because it analyzed nationwide health insurance claims data and followed more than 6,000 patients for over four years. We found that patients with ulcerative colitis faced a significantly higher risk of adverse outcomes, including the need to initiate corticosteroid therapy, after discontinuing immunomodulators."

Corresponding author Professor Byong Duk Ye of the Division of Gastroenterology at Asan Medical Center said, "The key finding of this study is that discontinuing immunomodulators produced different outcomes in Crohn's disease and ulcerative colitis, even though both are classified as inflammatory bowel disease. We expect these findings to provide important evidence for developing more personalized treatment strategies for individual patients."

The study was published in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association, which has an impact factor of 16.2.