The Risk of Relapse Associated With Discontinuation of 5-Aminosalicylates in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

BACKGROUND: Mesalamine (5-aminosalicylic acid, [5-ASA]) is the first-line therapeutic agent in mild-to-moderate ulcerative colitis (UC). The continuous use of 5-ASA involves costs, adverse effects, and delayed treatment escalation. In certain circumstances, such as in patients with Crohn disease (CD) or patients escalated to advanced therapies, discontinuation of 5-ASA may be feasible. However, the implications of withdrawal on disease outcomes remain unclear. AIMS: We sought to assess the relative risk (RR) of relapse in patients with quiescent UC or CD who discontinue 5-ASA compared with those who maintain treatment with 5-ASA. METHODS: A search of 5 databases was conducted from inception until July 2024. Eligible studies were selected and subjected to quality assessment. The studies were categorized into 6 clinically relevant cohorts, and the RR of relapse was analysed. RESULTS: A total of 7203 studies were identified, with 29 meeting inclusion criteria. The discontinuation of oral 5-ASA monotherapy was associated with a 60% increase in the risk of relapse in patients with UC (relative risk, 1.60; 95% C, 1.25-2.05; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] level of certainty, low). The withdrawal of rectal 5-ASA resulted in a RR of relapse of 2.03 (95% CI, 1.58-2.61; GRADE level of certainty, moderate). In contrast, in patients receiving immunomodulators and/or biologics, the cessation of 5-ASA was not associated with an increased risk of relapse (very low and low GRADE level of certainty, respectively). CONCLUSIONS: The discontinuation of oral or rectal 5-ASA monotherapy in patients with UC is associated with an increased risk of relapse. The data for discontinuation of 5-ASA in patients with UC or CD who are on immunomodulators and/or biologics is marginal for a meta-analysis; considering this limitation, these patients do not seem to have an increased risk of relapse upon discontinuation of 5-ASA, suggesting that monitored withdrawal may be a viable strategy.