Ulcerative Colitis Maintenance Treatment With 5-ASA
Ulcerative Colitis Maintenance Treatment With 5-ASA
Background 5-ASA-MMX (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis.
Aim To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study.
Methods In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for ≥1 month prior to the trial, with ≥1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months' treatment.
Results In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission (P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission (P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated.
Conclusions Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis.
5-aminosalicylic acid (5-ASA) is the recommended therapy for the induction and maintenance of remission of ulcerative colitis (UC). The drug acts topically at the colonic mucosa to reduce mucosal inflammation, yet because the active drug is rapidly absorbed in the stomach and small intestine, a number of oral formulations have been developed to deliver 5-ASA to the colon.
Whilst achieving effective delivery to the colon is vital, compliance with prescribed medication has been shown to be an important factor in UC treatment. Indeed, compliant patients substantially reduce their risk of disease flares. In a pilot trial to assess compliance rates following once-daily or multiple-daily 5-ASA dosing schedules in patients with quiescent UC, significantly higher compliance rates were demonstrated in the once-daily group compared with multiple-daily dosing groups (100 vs. 70%, respectively; P = 0.04). Indeed, compliance with prescribed medication was emphasized in a recent Cochrane meta-analysis, which concluded that future trials investigating UC treatment should examine enhancing patient adherence with their medication, rather than comparing the efficacy of various 5-ASA agents.
Mesalazine with MMX Multi Matrix System (MMX) technology (Mesavancol, Giuliani, S.p.A., Milan, Italy; hereafter referred to as 5-ASA-MMX) is a novel, high-strength (1.2 g/tablet) formulation of 5-ASA, designed for once-daily dosing, that has been approved for the induction and maintenance of clinical and endoscopic remission in patients with mild-to-moderate UC in Europe and for the induction of remission of active mild-to-moderate UC in the US. This formulation of 5-ASA utilizes MMX technology comprising lipophilic and hydrophilic excipients enclosed within a gastro-resistant, pH-dependent coating. The gastro-resistant coating is thought to delay the release of 5-ASA until the tablet is exposed to a pH of 7 or higher, (normally in the terminal ileum). The tablet core consists of hydrophilic excipients (that are thought to cause the tablet to swell to a viscous gel mass, slowing the release of 5-ASA) and lipophilic excipients (that are thought to slow the penetration of aqueous fluids into the tablet core), which are believed to prolong exposure of the colonic mucosa to 5-ASA. As the tablet core and surrounding gel mass progress through the colon, it is thought that pieces of the gel mass gradually break away from the core, slowly releasing 5-ASA. Previous trials have demonstrated the efficacy of 5-ASA-MMX over placebo for both the induction and maintenance of remission.
The present study is the first comparative, 12-month maintenance trial to examine efficacy as the primary endpoint. In this study, we evaluated the efficacy and safety of 5-ASA-MMX 2.4 g/day administered once daily, compared with Asacol delayed-release mesalazine (Giuliani, S.p.A., Milan, Italy; 2.4 g/day) administered twice daily, over 12 months, for the maintenance of left-sided UC.
Abstract and Introduction
Abstract
Background 5-ASA-MMX (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis.
Aim To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study.
Methods In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for ≥1 month prior to the trial, with ≥1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months' treatment.
Results In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission (P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission (P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated.
Conclusions Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis.
Introduction
5-aminosalicylic acid (5-ASA) is the recommended therapy for the induction and maintenance of remission of ulcerative colitis (UC). The drug acts topically at the colonic mucosa to reduce mucosal inflammation, yet because the active drug is rapidly absorbed in the stomach and small intestine, a number of oral formulations have been developed to deliver 5-ASA to the colon.
Whilst achieving effective delivery to the colon is vital, compliance with prescribed medication has been shown to be an important factor in UC treatment. Indeed, compliant patients substantially reduce their risk of disease flares. In a pilot trial to assess compliance rates following once-daily or multiple-daily 5-ASA dosing schedules in patients with quiescent UC, significantly higher compliance rates were demonstrated in the once-daily group compared with multiple-daily dosing groups (100 vs. 70%, respectively; P = 0.04). Indeed, compliance with prescribed medication was emphasized in a recent Cochrane meta-analysis, which concluded that future trials investigating UC treatment should examine enhancing patient adherence with their medication, rather than comparing the efficacy of various 5-ASA agents.
Mesalazine with MMX Multi Matrix System (MMX) technology (Mesavancol, Giuliani, S.p.A., Milan, Italy; hereafter referred to as 5-ASA-MMX) is a novel, high-strength (1.2 g/tablet) formulation of 5-ASA, designed for once-daily dosing, that has been approved for the induction and maintenance of clinical and endoscopic remission in patients with mild-to-moderate UC in Europe and for the induction of remission of active mild-to-moderate UC in the US. This formulation of 5-ASA utilizes MMX technology comprising lipophilic and hydrophilic excipients enclosed within a gastro-resistant, pH-dependent coating. The gastro-resistant coating is thought to delay the release of 5-ASA until the tablet is exposed to a pH of 7 or higher, (normally in the terminal ileum). The tablet core consists of hydrophilic excipients (that are thought to cause the tablet to swell to a viscous gel mass, slowing the release of 5-ASA) and lipophilic excipients (that are thought to slow the penetration of aqueous fluids into the tablet core), which are believed to prolong exposure of the colonic mucosa to 5-ASA. As the tablet core and surrounding gel mass progress through the colon, it is thought that pieces of the gel mass gradually break away from the core, slowly releasing 5-ASA. Previous trials have demonstrated the efficacy of 5-ASA-MMX over placebo for both the induction and maintenance of remission.
The present study is the first comparative, 12-month maintenance trial to examine efficacy as the primary endpoint. In this study, we evaluated the efficacy and safety of 5-ASA-MMX 2.4 g/day administered once daily, compared with Asacol delayed-release mesalazine (Giuliani, S.p.A., Milan, Italy; 2.4 g/day) administered twice daily, over 12 months, for the maintenance of left-sided UC.