Prolonged-release mesalazine - A review of its therapeutic potential in ulcerative colitis and Crohn's disease

Prolonged-release mesalazine (Pentasa(R)(2)) consists of ethylcellulose-coa ted microgranules from which mesalazine (known in the US as mesalamine) is released in the small and large intestine in a diffusion-dependent manner. Dose-dependent improvements in clinical and endoscopic parameters have been reported with prolonged-release mesalazine 2 and 4 g/day in clinical trial s in patients with mild to moderately active ulcerative colitis. Induction of clinical and endoscopic remission was achieved in more patients receivin g a daily dosage of 4 g/day than in those receiving placebo. In patients with ulcerative colitis in remission, prolonged-release mesalaz ine is effective in reducing the rate of relapse. Higher dosages tend to be more effective, and a 12-month remission rate of 64% has been reported for patients treated with a 4g daily dosage of this formulation. Comparative d ata indicate that prolonged-release mesalazine has similar efficacy in main taining remission to molar equivalent doses of sulfasalazine. Data from a study in patients with mild to moderately active Crohn's diseas e indicates that higher dosages (4 g/day) of prolonged-release mesalazine a re more effective than placebo in reducing disease activity. After 16 weeks ' treatment, 64% of patients receiving a 4 g/day dosage experienced clinica l improvement and 43% attained remission. In studies of patients in remissi on of Crohn's disease, the formulation appears to be more effective in prev enting relapse in patients with isolated small bowel disease than in those with colonic involvement. The tolerability profile of oral prolonged-release mesalazine is similar to that of placebo and the incidence of adverse events does not appear to be dose-related. Nausea/vomiting. diarrhoea, abdominal pain and dyspepsia occu r most frequently, although their incidence is low. Reports of nephrotoxici ty during prolonged-release mesalazine treatment are rare. Conclusions: Oral prolonged-release mesalazine is effective for maintenance and induction of remission of mild to moderately active colitis, both in p atients with distal disease and in those with pancolitis. The formulation h as similar efficacy to that of equimolar concentrations of sulfasalazine. P rolonged-release mesalazine also appears to be effective in the treatment o f Crohn's disease, and maintenance therapy is of particular value in patien ts with isolated small bowel involvement. Evidence suggests that higher dos ages (3 to 4 g/day) of prolonged-release mesalazine have additional therape utic benefits over lower dosages in patients with inflammatory bowel diseas e without increasing the incidence of adverse events.