Assessing the Clinical and Endoscopic Efficacy of Extended Treatment Duration with Different Doses of Mesalazine for Mild-to-Moderate Ulcerative Colitis beyond 8 Weeks of Induction

Abstract

Introduction: High-strength mesalazine formulations play an important role in providing a convenient option to increase the dose in ulcerative colitis (UC) patients and therefore avoiding the switch to another therapeutic class. Higher doses of mesalazine may be required during periods of remission in order to prevent relapse. Aim: To investigate clinical outcomes of three mesalazine maintenance doses adapted for post induction response. Methods: In this post-hoc analysis, 675 UC patients entered an open label extension study for a total of 38 weeks (including 8-12 week induction period with 3.2 g/day mesalazine). After the induction period they were separated into three groups: remitters (in clinical and endoscopic remission), responders (decrease in Partial Mayo Clinic Score (PMCS) of ≥ 2 points and ≥ 30% from week 0) and non-responders (failed to achieve endoscopic and clinical response at week 8) and received 1.6 g/day, 3.2 g/day or 4.8 g/day of mesalazine (using a new 1600 mg mesalazine tablet), respectively. Results: 133/202 (65.8%), 108/274 (39.4%) and 59/199 (29.6%) patients achieved clinical and endoscopic remission at week 38 with 1.6 g/day, 3.2 g/day and 4.8 g/day, respectively. At week 38, 142/202 (70.3%), 93/274 (33.9%) and 61/199 (30.7%) patients achieved clinical remission (stool score of 0 and rectal bleeding score of 0) with 1.6 g/day, 3.2 g/day and 4.8 g/day, respectively. Conclusions: Patients partially responding or not responding to an initial induction dose of 3.2 g/day mesalazine could benefit from an extended treatment period at the same dose, or an increase to 4.8 g/day in an attempt to achieve combined clinical and endoscopic remission.

Inflammatory Bowel Disease Therapies and Acute Liver Injury

“…Mesalazine is the 5-ASA compound most commonly prescribed to patients with ulcerative colitis (UC) or Crohn's disease for the maintenance of remission and in association with corticosteroids for the induction of remission in mild-moderate active forms. The incidence of mesalazine-associated hepatotoxicity remains low [20,21]. Adverse hepatic effects associated with mesalazine range from a mild asymptomatic increase in hepatic cytolysis rates to idiosyncratic cholestasis and in most cases these events resolve rapidly with discontinuation of the drug [22].…”

Inflammatory Bowel Disease Therapies and Acute Liver Injury

“…Mesalazine is the aminosalicylate most commonly prescribed to patients with ulcerative colitis (UC) or Crohn’s disease for the maintenance of remission and in association with corticosteroids for the induction of remission in mild-moderate active forms. The incidence of mesalazine-associated hepatotoxicity remains low because mesalazine is minimally absorbed and mostly eliminated in the feces [ 23 , 24 ]. Adverse hepatic effects associated with mesalazine range from a mild asymptomatic increase in hepatic cytolysis rates to idiosyncratic cholestasis, and in most cases, these events resolve rapidly with discontinuation of the drug [ 25 ].…”