Endoscopically Measured Mucosal Healing Correlated with Response to Therapy in Moderately Active UC

Abstract

Purpose: Examine the correlation between endoscopically measured mucosal healing and response to therapy with delayed-release oral mesalamine 4.8g/day (investigational 800mg tab) and 2.4g/day (marketed 400mg tab) in patients with moderately active UC. Methods: Data from 2 Phase III, multi-center, randomized, double-blind, 6-week, controlled studies of similar design (ASCEND I&II) were pooled and analyzed. The primary endpoint was treatment success, pre-defined as improvement from baseline in the Physician's Global Assessment (PGA) accompanied by improvement in at least one other clinical assessment (stool frequency, rectal bleeding, patient functional assessment (PFA), or endoscopy findings) and no worsening in any of the remaining clinical assessments. Mucosal healing was defined as an endoscopy score of 0 or 1. PFA was based on a 4-point scale, 0 = “generally well” to 3 = “terrible.” Patients with moderately active UC (baseline PGA = 2) and baseline endoscopy score ≥2 were included in this analysis. The correlation between mucosal healing and treatment response and PFA was determined. Results: 423 analyzable patients with moderate UC were randomized in the 2 studies, of which 391 patients met the criteria for these analyses. The 2 treatment groups were balanced at baseline with regard to demographic characteristics, disease history, and disease state characteristics. Overall at 6 weeks, 67% of moderate UC patients who achieved treatment success also had mucosal healing (Kappa = 0.6938). This finding was consistent regardless of dose of 2.4g/day or 4.8g/day (Kappa = 0.7452 and 0.6046, respectively). This finding was also consistently present at 3-weeks (Kappa = 0.7173). An endoscopic score of 0 alone was poorly correlated with treatment success but did improve from 3 to 6 weeks (Kappa = 0.1176 and 0.2252 respectively). Regardless of dose or time, PFA correlated poorly with mucosal healing. Both doses of mesalamine were well tolerated, with adverse events comparable between 4.8g/day and 2.4g/day. Conclusions: This analysis demonstrates that successful treatment of moderately active UC with mesalamine is associated with improved mucosal integrity as early as 3 and 6 weeks. The lack of association between endoscopic improvement and PFA may be due to the fact that UC patients' general well-being involves more than mucosal healing.