Long-Term Benefit of Mesalamine Granules for Patients Who Achieved Corticosteroid-Induced Ulcerative Colitis Remission

Gary R Lichtenstein, Glenn L Gordon, Salam Zakko, Uma Murthy, Shahriar Sedghi, Ron Pruitt, Andrew C Barrett, Enoch Bortey, Craig Paterson, William P Forbes, Gary R Lichtenstein, Glenn L Gordon, Salam Zakko, Uma Murthy, Shahriar Sedghi, Ron Pruitt, Andrew C Barrett, Enoch Bortey, Craig Paterson, William P Forbes

Abstract

Background: Patients with ulcerative colitis (UC) who achieve remission with corticosteroids often relapse after tapering or discontinuation; alternative treatments limiting steroid exposure and UC relapse would be beneficial. It remains uncertain whether patients with corticosteroid-induced remission experience benefit with mesalamine granules (MG), a locally acting aminosalicylate extended-release capsule formulation for maintenance of UC remission in adults.

Aims: Efficacy and safety of MG 1.5 g once daily was evaluated in patients with UC in corticosteroid-induced remission.

Methods: Data from patients with previous corticosteroid use to achieve baseline UC remission were analyzed from two 6-month randomized, double-blind, placebo-controlled trials and a 24-month open-label extension (OLE). Six-month relapse-free rates were assessed using the revised Sutherland Disease Activity Index. UC-related adverse events (AEs) were recorded during the 30 months.

Results: Included were 158 steroid-treated patients in UC remission (MG, n = 105; placebo, n = 53) and 74/105 MG-treated patients who continued MG in the OLE. A significantly larger percentage of patients remained relapse-free at 6 months with MG (77.1 %) versus placebo (54.7 %; P = 0.006), with a 55 % reduction in relapse risk (hazard ratio [HR] 0.45; 95 % CI 0.25-0.79). There was a similar (49.2 %) reduction in risk of UC-related AEs at 6 months (HR 0.51; 95 % CI 0.31-0.84; P = 0.009) that was sustained during the OLE.

Conclusions: MG 1.5 g once daily administered for maintenance of corticosteroid-induced remission was associated with low risk of relapse and UC-related AEs. CLINICALTRIALS.GOV: NCT00744016, NCT00767728, and NCT00326209.

Keywords: Inflammatory bowel diseases; Mesalamine; Remission; Steroids; Ulcerative colitis.

Figures

Fig. 1
Fig. 1
Patient disposition for subpopulation of patients previously treated with corticosteroids for induction or maintenance of remission of ulcerative colitis during the two double-blind Phase 3 trials (MPUC3003 and MPUC3004) and the open-label extension trial (MPUC3005). MG mesalamine granules, OLE open-label extension. aSafety data not available for 4 patients (3 in the MG group and 1 in the placebo group)
Fig. 2
Fig. 2
Probability of remaining relapse-free during 6 months of treatment in patients previously treated with corticosteroids (MPUC3003 and MPUC3004, pooled). P value determined using Poisson regression analysis. MG mesalamine granules
Fig. 3
Fig. 3
Probability of remaining free from ulcerative colitis (UC)-related adverse events (AEs; defined as UC, hematochezia, or frequent bowel movements) during short-term treatment (MPUC3003 and MPUC3004, pooled) and long-term treatment (MPUC3005). MG mesalamine granules

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