Predictors of Ulcerative Colitis Relapse Following 5-ASA Dose Reduction

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Investigators outlined risk factors for ulcerative colitis relapse in patients undergoing dose reduction of oral 5-aminosalicylic acid.

Study data published in PLOS ONE outline risk factors for ulcerative colitis (UC) relapse in patients undergoing dose reduction of oral 5-aminosalicylic acid (5-ASA). In a study of patients whose 5-ASA dose was reduced during the clinical remission phase of UC, relapse was more common in those with a history of acute severe UC (ASUC). Patients without ASUC were significantly more likely to remain in remission over 52 weeks of follow-up.

This retrospective cohort study enrolled consecutive patients with UC in remission from the gastroenterology and hepatology department of Tokyo Medical University in Tokyo, Japan. Eligible patients underwent 5-ASA dose reduction between February 2012 and November 2017. All patients were in clinical remission prior to starting dose reduction.

Clinical disease activity was assessed using the partial Mayo score (pMayo); clinical remission was defined as a pMayo score of ≤1. A pMayo score exceeding 3 constituted clinical relapse. ASUC was defined as the passage of 6 or more bloody stools per day with the presence of 1 or more of the following Truelove and Witts criteria: pulse >90 beats per minute, temperature >37.8˚C, hemoglobin <105 g/L, or erythrocyte sedimentation rate >30 mm/h. Logistic regression was used to identify correlates of relapse within 52 weeks of initial dose reduction. Cumulative relapse-free survival rates were calculated using the Kaplan-Meier method.

The study cohort consisted of 70 patients with UC, among whom 18 (25.7%) relapsed during follow-up. Median age at baseline was 44 (interquartile range [IQR], 20-81) years. Median disease duration was 4.5 (IQR, 0-37) years. Median time in remission was 1 (IQR, 1-10) years. Eight patients (11.4%) had a history of ASUC.

In multivariable regression models, ASUC was identified as an independent predictor of relapse (odds ratio [OR], 21; 95% CI, 1.50-293.2). Per Kaplan-Meier survival analyses, the cumulative relapse-free survival rate within 52 weeks was 22.2% among patients with ASUC compared with 82.0% among patients without ASUC (P <.001). Relapse-free survival in the overall cohort was 74.3%.

Of the 18 patients who experienced relapse, 11 were treated with a high dose of oral 5-ASA, 6 with a high dose of oral 5-ASA and topical therapy, and 1 with oral corticosteroids. All 18 patients subsequently re-entered remission. No patients were hospitalized during follow-up.

Based on these data, 5-ASA dose reductions should be undertaken with caution, particularly in patients with a history of ASUC. This study had limitations, including the small cohort size and the absence of colonoscopy data in many patients. Replication in a larger cohort with endoscopic data is necessary.

“Patients with a history of ASUC have an increased risk of relapse compared with patients without a history of ASUC,” investigators wrote. “Therefore, 5-ASA doses should be reduced with caution in patients with a history of ASUC, as it is more likely to induce a relapse than in patients without a history of ASUC,” they concluded.


Madarame A, Fukuzawa M, Yamauchi Y, et al. Predictive factors of relapse after dose reduction of oral 5-aminosalicylic acid in patients with ulcerative colitis in the remission phase. PLoS One. 2021;16(8):e0255620. doi:10.1371/journal.pone.0255620