Previous History of Steroid Use Does Not Preclude Treatment with Mesalamine in Ulcerative Colitis (UC)

Abstract

Purpose: To determine effect of high dose delayed-release oral mesalamine (4.8 g/d) in patients with moderately active UC previously treated with oral or IV steroids. Methods: Data from 2 multi-center, randomized, double-blind, active-controlled studies of similar design (ASCEND I&II) were combined and analyzed. Efficacy and safety of delayed-release mesalamine 4.8 g/d (investigational 800 mg tab) was compared with 2.4 g/d (Asacol, marketed 400 mg tab) for treatment of mildly and moderately active UC. The primary efficacy variable in the combined analysis was treatment success in patients with moderately active UC (defined as baseline Physician's Global Assessment [PGA] score = 2). Treatment success was defined as improvement from baseline at week 6 in PGA accompanied by improvement in at least one clinical assessment (stool frequency, rectal bleeding, patient functional assessment [PFA], or sigmoidoscopy findings) and no worsening in any of the remaining clinical assessments. Improvement was defined as a decrease from baseline of at least 1 point based on a 4-point scale (0–3). Improvement in the individual clinical assessments was also assessed. Results: A total of 423 analyzable patients with moderate UC were randomized in the 2 studies, of which 137 patients had received previous oral or IV steroid therapy. The incremental benefit of 4.8 g/d over 2.4 g/d was apparent in patients previously treated with steroids:Table: Treatment Success at Week 6 in Moderate UC PatientsImprovement in the individual clinical assessments further support the response of 4.8 g/d in patients previously treated with steroids:Table: Improvement at Week 6 In Moderate UC Patients Previously Treated with SteroidsThe 4.8 g/d dose of mesalamine was well tolerated, with adverse events comparable to 2.4 g/d. Conclusion: A previous history of steroid use does not preclude treatment with mesalamine. There is a role for mesalamine in moderate UC patients previously treated with steroids. UC patients with moderately active disease previously treated with oral or IV steroids respond better to higher initial doses (4.8 g/d) of mesalamine.