Efficacy and Safety of Discontinuing 5-ASA in Patients With Inflammatory Bowel Disease

In inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) is widely used as a first-line treatment for ulcerative colitis (UC) and is still prescribed for Crohn's disease (CD). However, for patients who do not respond to conventional therapy, anti-tumor necrosis factor (anti-TNF) agents have become an effective alternative. This has led to ongoing debate about whether continued use of 5-ASA is necessary after transitioning to anti-TNF therapy.

Recent retrospective studies have reported that discontinuing 5-ASA after initiating anti-TNF therapy in UC and CD patients does not increase the risk of clinical adverse outcomes such as new steroid use, hospitalization, or bowel surgery. However, a study based on U.S. data had a median follow-up period of less than one year, making it difficult to assess long-term effects. Additionally, studies on relapse risk after discontinuing 5-ASA have identified younger age, extensive disease, and frequent relapses as risk factors, but detailed analyses for patients receiving anti-TNF therapy remain insufficient.

Another critical issue is the economic burden of continued 5-ASA treatment. In South Korea, the annual cost of the most commonly used 5-ASA formulations constitutes a significant portion of overall healthcare expenses. Discontinuing 5-ASA could reduce treatment costs, simplify therapy, improve patient adherence, and minimize adverse effects associated with polypharmacy. Regarding colorectal cancer (CRC) prevention, recent trends indicate a decreasing incidence of CRC in IBD patients. Since mucosal inflammation is considered a primary driver of CRC, additional 5-ASA use may not be necessary if mucosal healing is achieved through biologics or small-molecule therapies.

Accordingly, this study aims to evaluate the long-term outcomes of discontinuing 5-ASA in UC and CD patients receiving stable biologic or immunomodulator therapy.

Inclusion criteria

• Diagnosis

o Patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) based on standard diagnostic criteria, including clinical, endoscopic, and histologic findings.

• Treatment Status

• Patients who have been continuously treated with biologic agents (e.g., anti-TNF agents, integrin inhibitors, JAK inhibitors) or immunomodulators (e.g., azathioprine, methotrexate) for at least three months.
• Patients who have been on a stable dose of 5-ASA (mesalamine) for at least three months before study enrollment.
• Disease Activity

o Patients in clinical remission for at least three months, as defined by the Mayo score for UC or the Crohn's Disease Activity Index (CDAI) for CD.

• Age

o Adults aged 19 years or older.

• Informed Consent

o Patients capable of providing written informed consent for study participation.

• Compliance with Study Protocol

o Patients who can adhere to the study protocol and visit schedule.

• General Health Condition

o Patients without severe medical conditions that could impact the study or patient safety, such as significant cardiac, renal, or hepatic diseases.

• No recent medication changes
• Patients who have not had any new prescriptions or dose adjustments of corticosteroids, antibiotics, or other medications that could affect IBD within a specified period (e.g., four weeks) before enrollment.

Exclusion criteria

• Patients with severe active UC or CD at the time of study enrollment.
• Patients who have been recently hospitalized for IBD-related reasons or undergone IBD-related surgery within three months before enrollment.
• Patients who have had dose modifications of biologics, immunomodulators, or corticosteroids for IBD within three months before enrollment.
• Patients receiving concomitant therapy with other medications that may affect disease activity (e.g., additional anti-inflammatory agents, IBD-related antibiotics).
• Patients with severe cardiac, renal, or hepatic disease or other medical conditions that could interfere with the study.
• Pregnant or breastfeeding women.
• Patients with known allergies or intolerance to 5-ASA or related medications.
• Patients currently participating in another clinical study that may interfere with this study.
• Patients unable to provide informed consent or unlikely to comply with the study protocol and visit schedule.
• Patients with a history of non-response or intolerance to their current biologic or immunomodulator therapy.
• Patients with a history of severe psychiatric disorders that may affect their ability to participate in the study.