ORAL MESALAMINE DOSING AND RESPONSE RATES IN ULCERATIVE COLITIS: A SYSTEMATIC REVIEW AND DOSE-RESPONSE META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract Objective Oral mesalamine remains the cornerstone of treatment for mild-to-moderate ulcerative colitis (UC), yet the optimal dose for induction and maintenance of remission remains uncertain, with clinical guidelines suggesting diminishing benefits above 2.4-3 g/day. We aimed to evaluate the association between daily oral mesalamine dose and clinical efficacy using continuous dose-response meta-regression. METHODS We performed a systematic review and dose-response meta-analysis of randomized controlled trials assessing oral mesalamine in adult UC patients. Arm-level data from 55 study arms across 22 RCTs (n = 5,528) were analyzed. A one-stage random-effects meta-regression model was used to analyze the relationship between dose (g/day) and remission, partial improvement, and efficacy for induction and maintenance therapy. Linear and restricted cubic spline models were fitted. The risk of bias and certainty of evidence was assessed using RoB 2.0 and GRADE. RESULTS No statistically significant association was observed between increasing mesalamine dose and induction of overall remission (β = -0.14; p = 0.073), clinical remission (β = -0.16; p = 0.077), or maintenance of remission (β = 0.08; p = 0.456). However, a significant inverse association was found for clinical response during induction (β = -0.20; p = 0.004), suggesting higher doses may be linked to lower reported response rates, potentially due to measurement variability or reporting bias. Spline modelling did not improve model fit. Certainty of evidence was moderate for induction and low for maintenance. CONCLUSIONS Our findings support the use of standard-dose oral mesalamine (2-3 g/day) for most patients with UC. Higher doses may offer minimal additional benefit and should be individualized based on clinical context.