Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared to 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial

Abstract

Background: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease.

Patients and methods: A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline.

Results: Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated.

Conclusions: Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day.

Figure 1)

Patient disposition. Patients who could not be analyzed at week 6 included those who completed week 6 but were missing at least one symptom score (one patient in each treatment group), and patients who did not complete the study due to voluntary withdrawal (two patients in the 2.4 g/day delayed-release oral mesalamine group and six patients in the 4.8 g/day group) or to protocol deviations (one patient in the 2.4 g/day delayed-release oral mesalamine group and four patients in the 4.8 g/day group). ITT Intention-to-treat

Figure 2)

Asacol (Proctor & Gamble Pharmaceuticals, USA) treatment outcomes at weeks 3 and 6 in all patients with mildly to moderately active ulcerative colitis

Figure 3)

The total Inflammatory Bowel Disease Questionnaire (IBDQ) scores and all subcategory scores for patients with mildly to moderately active ulcerative colitis improved significantly from baseline to weeks 3 and 6 in both treatment groups (Asacol, Proctor & Gamble Pharmaceuticals, USA). *Significant difference in the between-treatment comparison using Wilcoxon’s signed rank test (P≤0.05)

Figure 4)

Treatment success in the subgroup of patients with moderately active ulcerative colitis who were administered delayed-release oral mesalamine (Asacol, Proctor & Gamble Pharmaceuticals, USA) at a dose of either 2.4 g/day or 4.8 g/day. *Significant difference in between-treatment comparison using Wilcoxon’s signed rank test (P=0.0384)

Figure 5)

Mean change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) scores at weeks 3 and 6 in the subgroup of patients with moderately active ulcerative colitis who were administered delayed-release oral mesalamine (Asacol, Proctor & Gamble Pharmaceuticals, USA) at doses of either 2.4 g/day or 4.8 g/day. *Significant difference in between-treatment comparison using Wilcoxon’s signed rank test (P≤0.05)