MMX Mesalamine to Maintain Remission of Ulcerative Colitis
MMX Mesalamine to Maintain Remission of Ulcerative Colitis
OBJECTIVES: Treatment with mesalamine to maintain endoscopic remission (mucosal healing) of ulcerative colitis (UC) has been shown to reduce the risk of relapse and is the recommended first-line maintenance therapy. To improve treatment adherence, a mesalamine formulation that can be administered once-daily, MMX® mesalamine (Lialda; Shire Pharmaceuticals LLC, Wayne, PA), was developed. This study was conducted to determine the efficacy and safety of once-daily MMX mesalamine compared with twice-daily delayed-release mesalamine (Asacol; Warner Chilcott, Dublin, Ireland) for maintaining endoscopic remission in patients with UC.
METHODS: A multicenter, randomized, double-blind, 6-month, active-control trial was conducted to assess the non-inferiority of once-daily MMX mesalamine 2.4 g/day compared with twice-daily delayed-release mesalamine at a total daily dose of 1.6 g/day in patients with UC in endoscopic remission. The primary end point was maintenance of endoscopic remission at month 6 in the per-protocol (PP) population.
RESULTS: Overall, 826 patients were randomized and dosed. The primary objective (non-inferiority) was met. At month 6, 83.7 and 77.8% of patients receiving MMX mesalamine in the PP and intent-to-treat (ITT) populations, respectively, had maintained endoscopic remission compared with 81.5% (PP) and 76.9% (ITT) of patients receiving delayed-release mesalamine (95% confidence interval for difference: –3.9%, 8.1% (PP); –5.0%, 6.9% (ITT)). Time to relapse was not significantly different between the two treatment groups (log-rank test, P=0.5116 (PP); P=0.5455 (ITT)). The proportion of patients with adverse events was 37.1 and 36.0% in patients receiving MMX mesalamine and delayed-release mesalamine, respectively.
CONCLUSIONS: Once-daily dosing of MMX mesalamine 2.4 g/day was shown to be well tolerated and non-inferior to twice-daily dosing with delayed-release mesalamine 1.6 g/day for maintenance of endoscopic remission in patients with UC.
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, which extends from the anal verge and can involve progressive contiguous segments of the colon up to and including the entire colon. The incidence of UC is estimated at six to eight new cases per 100,000 people per year in Western countries, and has also been rising in other parts of the world. Patients with active UC typically present with signs and symptoms of bloody diarrhea, abdominal pain, general malaise, and sometimes iron deficiency anemia, all of which can lead to an impaired quality of life and absence from work.
The cornerstone of treatment for mild-to-moderate UC is mesalamine, a topically acting anti-inflammatory agent that is administered orally and/or rectally via enemas, foams, or suppositories. Mesalamine is the first-line treatment of choice for UC because of its favorable toxicity profile, relatively rapid onset of action, and probable chemoprevention properties against the development of colorectal dysplasia and cancer.
While patients with more severe UC may need treatment with corticosteroids, immunosuppressive agents and/or antitumor necrosis factor antibody therapy with infliximab, the majority of patients with mild-to-moderate disease can be managed successfully with mesalamine alone. The medical treatment of UC has traditionally been divided into two parts: the induction of clinical remission (defined as the point that the patient becomes free from symptoms); and maintenance of remission (defined as a continuation of a symptom-free state and a healed colonic mucosa). The gold standard for demonstrating maintenance of remission is maintenance of endoscopic remission, also defined in the protocol for this study as maintenance of mucosal healing.
The efficacy of mesalamine to maintain clinical remission and/or mucosal healing has been established in several randomized controlled trials.
The current trial was designed to examine the efficacy of a once-daily formulation of mesalamine (MMX (MMX is a registered trademark of Cosmo Technologies, Wicklow, Ireland) mesalamine) 2.4 g/day as compared with twice-daily delayed-release mesalamine for a total daily dose of 1.6 g/day for maintenance of endoscopic remission (mucosal healing) in patients with UC who had been treated for acute relapse in the past 12 months. The primary end point of this trial differs from most other mesalamine maintenance trials that have predominantly focused on maintenance of clinical remission. Maintenance of mucosal healing, as documented by endoscopy, has become an important goal in the treatment of patients with UC. Indeed, several recent studies have demonstrated that remission with mucosal healing is associated with a significant reduction in the number of relapses compared with clinical remission alone.
Abstract and Introduction
Abstract
OBJECTIVES: Treatment with mesalamine to maintain endoscopic remission (mucosal healing) of ulcerative colitis (UC) has been shown to reduce the risk of relapse and is the recommended first-line maintenance therapy. To improve treatment adherence, a mesalamine formulation that can be administered once-daily, MMX® mesalamine (Lialda; Shire Pharmaceuticals LLC, Wayne, PA), was developed. This study was conducted to determine the efficacy and safety of once-daily MMX mesalamine compared with twice-daily delayed-release mesalamine (Asacol; Warner Chilcott, Dublin, Ireland) for maintaining endoscopic remission in patients with UC.
METHODS: A multicenter, randomized, double-blind, 6-month, active-control trial was conducted to assess the non-inferiority of once-daily MMX mesalamine 2.4 g/day compared with twice-daily delayed-release mesalamine at a total daily dose of 1.6 g/day in patients with UC in endoscopic remission. The primary end point was maintenance of endoscopic remission at month 6 in the per-protocol (PP) population.
RESULTS: Overall, 826 patients were randomized and dosed. The primary objective (non-inferiority) was met. At month 6, 83.7 and 77.8% of patients receiving MMX mesalamine in the PP and intent-to-treat (ITT) populations, respectively, had maintained endoscopic remission compared with 81.5% (PP) and 76.9% (ITT) of patients receiving delayed-release mesalamine (95% confidence interval for difference: –3.9%, 8.1% (PP); –5.0%, 6.9% (ITT)). Time to relapse was not significantly different between the two treatment groups (log-rank test, P=0.5116 (PP); P=0.5455 (ITT)). The proportion of patients with adverse events was 37.1 and 36.0% in patients receiving MMX mesalamine and delayed-release mesalamine, respectively.
CONCLUSIONS: Once-daily dosing of MMX mesalamine 2.4 g/day was shown to be well tolerated and non-inferior to twice-daily dosing with delayed-release mesalamine 1.6 g/day for maintenance of endoscopic remission in patients with UC.
Introduction
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, which extends from the anal verge and can involve progressive contiguous segments of the colon up to and including the entire colon. The incidence of UC is estimated at six to eight new cases per 100,000 people per year in Western countries, and has also been rising in other parts of the world. Patients with active UC typically present with signs and symptoms of bloody diarrhea, abdominal pain, general malaise, and sometimes iron deficiency anemia, all of which can lead to an impaired quality of life and absence from work.
The cornerstone of treatment for mild-to-moderate UC is mesalamine, a topically acting anti-inflammatory agent that is administered orally and/or rectally via enemas, foams, or suppositories. Mesalamine is the first-line treatment of choice for UC because of its favorable toxicity profile, relatively rapid onset of action, and probable chemoprevention properties against the development of colorectal dysplasia and cancer.
While patients with more severe UC may need treatment with corticosteroids, immunosuppressive agents and/or antitumor necrosis factor antibody therapy with infliximab, the majority of patients with mild-to-moderate disease can be managed successfully with mesalamine alone. The medical treatment of UC has traditionally been divided into two parts: the induction of clinical remission (defined as the point that the patient becomes free from symptoms); and maintenance of remission (defined as a continuation of a symptom-free state and a healed colonic mucosa). The gold standard for demonstrating maintenance of remission is maintenance of endoscopic remission, also defined in the protocol for this study as maintenance of mucosal healing.
The efficacy of mesalamine to maintain clinical remission and/or mucosal healing has been established in several randomized controlled trials.
The current trial was designed to examine the efficacy of a once-daily formulation of mesalamine (MMX (MMX is a registered trademark of Cosmo Technologies, Wicklow, Ireland) mesalamine) 2.4 g/day as compared with twice-daily delayed-release mesalamine for a total daily dose of 1.6 g/day for maintenance of endoscopic remission (mucosal healing) in patients with UC who had been treated for acute relapse in the past 12 months. The primary end point of this trial differs from most other mesalamine maintenance trials that have predominantly focused on maintenance of clinical remission. Maintenance of mucosal healing, as documented by endoscopy, has become an important goal in the treatment of patients with UC. Indeed, several recent studies have demonstrated that remission with mucosal healing is associated with a significant reduction in the number of relapses compared with clinical remission alone.
Source...