Progression to Colorectal Neoplasia in Ulcerative Colitis: Effect of Mesalamine

Background & Aims: Some studies have suggested that mesalamine can prevent the development of colorectal cancer in patients with ulcerative colitis (UC). The aim of this study was to compare rates of progression with advanced neoplasia in patient cohorts with UC taking low and high doses of mesalamine and to determine where in the process of neoplastic progression mesalamine might act. Methods: Three cohorts of UC patients were identified from an institutional database: 311 patients with no dysplasia (NoD), 56 with indefinite dysplasia (IND), and 26 with flat low-grade dysplasia (fLGD). The impact of mesalamine exposure on the subsequent development of advanced neoplasia (high-grade dysplasia or colorectal cancer) was assessed using life-table methods. Results: Seventeen of 311 patients with NoD progressed to advanced neoplasia (5-year rate, 1.1%). This rate was lower than the 5-year rate for the IND (9%; P = .02 vs NoD) and fLGD (45%; P < .001 vs NoD and P = .001 vs IND) cohorts. Among the NoD cohort, the hazard ratio for mesalamine users versus nonusers was 0.70 (95% confidence interval, 0.20-2.44), and for each 1 g/d increase in dose, the hazard ratio was 0.92 (95% confidence interval, 0.58-1.47). For patients with IND, no patients on greater than 2 g/d progressed versus 13.8% on low-dose mesalamine (P = .11). For fLGD, 62.5% on high dose progressed, versus 27.8% on low dose (P = .054). Conclusions: In long-standing UC, patients with fLGD have a higher rate of progression to advanced neoplasia than those with NoD or IND. However, at none of these stages of disease did mesalamine use show definitive chemopreventive activity.