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      Once-daily MMX mesalamine for the treatment of mild-to-moderate ulcerative colitis

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          Abstract

          First-line therapies in the treatment of patients with mild-to-moderate ulcerative colitis are sulfasalazine or one of the mesalamine derivatives. Mesalamine is popular given its safety profile and reasonable efficacy in many patients. However, compliance is poor with regimens demanding large number of pills dosed multiple times a day and non-compliance has been correlated with disease relapse. Mesalamine requires direct contact with the inflamed colonic mucosa. To avoid proximal absorption, a variety of delivery systems has been utilized to time the release of active mesalamine to the areas affected by colitis. The most common mesalamine release mechanisms include azo-bond prodrug carriers, pH-dependent dissolution, and moisture-sensitive product dispersion. Novel technology has resulted in the development and FDA-approval of a multi-matrix release (MMX) mesalamine. Pharmacodynamic studies suggest a reliable drug delivery system with homogenous release throughout the entire colon. By incorporating the largest amount of mesalamine (1.2 g) per pill, this new product dramatically decreases the number of pills needed to attain a therapeutic daily dosage, and is the first agent approved at once-daily dosing. These factors are expected to increase patient compliance with prescribed mesalamine dosing, and in turn decrease relapse rates of active ulcerative colitis.

          Most cited references74

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          The risk of colorectal cancer in ulcerative colitis: a meta-analysis.

          Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2-4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8). Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.
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            Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial.

            To assess the safety and efficacy of a preparation of mesalazine (5-aminosalicylic acid) coated with a pH dependent resin (Eudragit L) as compared with sulphasalazine in patients with active mild to moderate ulcerative colitis. Eight week randomised double blind parallel group study. Forty six gastroenterology outpatient clinics in seven countries. Two hundred and twenty patients aged 18-70 who met the following criteria: clinical activity index greater than or equal to 6 and endoscopic index greater than or equal to 4; no concomitant treatment for ulcerative colitis; no hypersensitivity to salicylates or sulphonamides. Of the 164 patients eligible for efficacy analysis, 87 received the coated preparation of mesalazine and 77 sulphasalazine. Most of the remaining patients (28 in each group) were ineligible for the efficacy analysis because of treatment with steroid enemas. All pretrial characteristics were comparable in the two treatment groups. Coated mesalazine (Mesasal) 1.5 g daily or sulphasalazine 3.0 g daily for eight weeks. Compliance monitored by pill counts. Clinical and endoscopic remission. Clinical activity measured by daily diary cards, assessment by investigators, and laboratory findings. Endoscopic evaluation at week 8. After four weeks 50 of 70 patients (71%) taking coated mesalazine and 38 of 58 (66%) taking sulphasalazine had achieved remission of their disease by eight weeks remission rates were 74% (37/50 patients) and 81% (35/43) in the two treatment groups respectively. Endoscopic remission at eight weeks was recorded in 20 of 41 patients (49%) taking coated mesalazine and 18 of 38 (47%) taking sulphasalazine. There was a higher incidence of adverse events among patients taking sulphasalazine (25/105; 24%) than among those taking coated mesalazine (16/115; 14%). Mesalazine coated with Eudragit L is a safe, logical alternative to sulphasalazine.
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              Prevalence of nonadherence with maintenance mesalamine in quiescent ulcerative colitis.

              There are scant data regarding outpatient adherence in quiescent ulcerative colitis aside from patients enrolled in controlled clinical trials. We conducted a prevalence study to determine the medication adherence rate of maintenance therapy and to identify possible risk factors for nonadherence. Outpatients with clinically quiescent ulcerative colitis for >6 months on maintenance mesalamine (Asacol, Procter and Gamble, Cincinnati, OH) were eligible. Patients were interviewed regarding disease history, and demographics were obtained from medical records. Refill information for at least 6 months was obtained from computerized pharmacy records. Adherence was defined as at least 80% consumption of supply dispensed. Using nonadherence as the outcome of interest, stratified analysis and regression modeling were used to identify significant associations. Data were complete for the 94 patients recruited. The overall adherence rate was found to be 40%. The median amount of medication dispensed per patient was 71% (8-130%) of the prescribed regimen. Nonadherent patients were more likely to be male (67% vs 52%, p < 0.05), single (68% vs 53%, p = 0.04), and to have disease limited to the left side of the colon versus pancolitis (83% vs 51%, p < 0.01). Sixty-eight percent of patients who took more than four prescription medications were found to be nonadherent versus only 40% of those patients taking fewer medications (p = 0.05). Age, occupation, a family history of inflammatory bowel disease, length of remission, quality-of-life score, or method of recruitment (telephone interview vs clinical visit) were not associated with nonadherence. Logistic regression identified that a history of more than four prescriptions (odds ratio [OR] 2.5 [1.4-5.7]) and male gender (OR 2.06 [1.17-4.88]) increased the risk of nonadherence. Two statistically significant variables, which were protective against nonadherence, were endoscopy within the past 24 months (OR 0.96 [0.93-0.99]) and being married (OR 0.46 [0.39-0.57]). Nonadherence is associated with multiple concomitant medications, male gender, and single status. These patient characteristics may be helpful in targeting those patients at higher risk for nonadherence.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                October 2007
                October 2007
                : 3
                : 5
                : 919-927
                Affiliations
                [1 ]Pritzker Medical School, The University of Chicago Chicago, IL, USA
                [2 ]Clinical Inflammatory Bowel Disease, Department of Medicine, Section of Gastroenterology, The University of Chicago Medical Center Chicago, IL, USA
                Author notes
                Correspondence: Russell D Cohen 5841 S. Maryland Avenue, MC 4076, Chicago, IL 60637, USA Tel +1 773 702 0719 Fax +1 773 702 2182 Email rcohen@ 123456medicine.bsd.uchicago.edu
                Article
                2376087
                18473016
                fce31e21-5dda-417b-868e-69894ea8c3c2
                © 2007 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Review

                Medicine
                olsalazine,balsalazide,ulcerative colitis,sulfasalazine,mesalamine,inflammatory bowel disease
                Medicine
                olsalazine, balsalazide, ulcerative colitis, sulfasalazine, mesalamine, inflammatory bowel disease

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