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Mesalazine
Selected AbstractsPharmacokinetics of mesalazine pellets in children with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 5 2004Heleen Wiersma MD Abstract Mesalazine is a first-line drug in pediatric inflammatory bowel disease (IBD), and is customarily used to induce and maintain remission in mild to moderate disease. In children, pharmacokinetic data are scarce, and dosage recommendations are largely extrapolated from studies in adults. Aim of the study was to obtain the pharmacokinetic profile of a new mesalazine pellet formulation in children with ulcerative colitis and Crohn's colitis. A single oral dose of 20 mg/kg mesalazine was administered to 13 patients (age 6,16 years). Serial blood and urine sampling for determination of mesalazine and acetylmesalazine was performed before and during 24 hours following ingestion. Maximum plasma concentration of mesalazine (Cmax) was 1332 ng/mL (geometric mean, geometric coefficient of variation [CV]: 0.57), obtained 3.7 hours (tmax; CV: 0.31) after drug administration. Systemic exposure as determined by area under the plasma concentration-time curve (AUC0,, ) was 8712 ng/ml*h (CV: 0.44). Terminal half-life of elimination of mesalazine was 3.5 hours (t1/2; CV: 1.43). This study presents extensive pharmacokinetic data on mesalazine in children with mild-moderately active ulcerative colitis and Crohn's colitis. In comparison with previous experience in adults, pharmacokinetics of mesalazine administered as pellets appear to be similar in both populations. [source] Mesalazine 4 g daily given as prolonged-release granules twice daily and four times daily is at least as effective as prolonged-release tablets four times daily in patients with ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 3 2001Dr. Per G. Farup Abstract Background High doses of mesalazine usually result in an inconvenient dosage schedule and reduced compliance. The goal of this trial was to compare the effects of mesalazine 4 g daily given as prolonged-release granules in packets of 1 g with that of prolonged-release tablets of 0.5 g. Methods Two hundred twenty-seven patients with mild-to-moderate ulcerative colitis were randomized to treatment with two packets twice daily (Gr-b.i.d.), 1 packet four times daily (Gr-q.i.d.) or 2 tablets four times daily (Ta-q.i.d.) for 8 weeks. A disease activity index (ulcerative colitis disease activity index; UC-DAI) was calculated, and the granules were defined as noninferior to the tablets if the lower limit of the 95% CI for the differences was more than ,1 UC-DAI score unit. Results Noninferiority of the granules compared with the tablets was demonstrated. The mean improvement in the UC-DAI in the treatment groups Gr-b.i.d., Gr-q.i.d., and Ta-q.i.d. were 3.2, 2.9, and 2.4, respectively; the proportion of complete responders in the three groups 39%, 37%, and 31%, respectively. There were no differences in side effects. Conclusion Mesalazine 4 g daily given as prolonged-release granules twice and four times daily is at least as effective as prolonged-release tablets four times daily in patients with mild to moderate ulcerative colitis. The patients preferred the twice daily dosing. [source] Mesalazine with or without cholestyramine in the treatment of microscopic colitis: Randomized controlled trialJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2007Carlo Calabrese Abstract Background:, Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory diseases of the colon with a benign and sometimes relapsing course. Frequency among patients with chronic diarrhea and normal looking colonoscopy is around 10,15%. To date, treatment of CC and LC is not well defined. Data about these conditions are mostly derived from retrospective studies. The aim of the present study was to evaluate the response to treatment and the clinical course of CC and LC in a large group of patients prospectively diagnosed. Methods and Results:, A total of 819 patients underwent a colonoscopy because of chronic watery diarrhea and among them we found 41 patients with LC and 23 with CC. These patients were later randomized and assigned to treatment with mesalazine or mesalazine + cholestyramine for 6 months. Fifty-four patients (84.37%) had resolved diarrhea in less than 2 weeks. After 6 months a colonoscopy with biopsies was repeated. Clinical and histological remission was achieved in 85.36% of patients with LC and in 91.3% with CC, with a better result in patients with CC treated with mesalazine + cholestyramine. During a mean period of 44.9 months, 13% of patients relapsed; four with LC and three with CC. They were retreated for another 6 months. At the end of this period one patient with CC was still symptomatic and persistence of CC was confirmed at histology. Conclusions:, Treatment with mesalazine seems to be an effective therapeutic option for LC to date, while mesalazine + cholestyramine seems to be more useful in the treatment of CC. [source] Systematic review: molecular chemoprevention of colorectal malignancy by mesalazineALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010A. LYAKHOVICH Summary Background, Mesalazine (mesalamine) (5-ASA) is considered an anti-inflammatory drug for the treatment of inflammatory bowel disease. It is well tolerated by most patients and induces mucosal healing specifically in ulcerative colitis. Besides its anti-inflammatory properties, 5-ASA has been studied for cancer inhibitory activities as it seems to reduce colorectal cancer incidence in patients using this drug for long periods of time. However, detailed molecular mechanisms of drug action are vague. Aims, To evaluate known molecular mechanisms of 5-ASA on chemoprevention of colorectal malignancy. Methods, Systematic review with search terms ,5 aminosalicylic acid, mesalazine, 5-ASA, mesalazine, molecular mechanisms, chemoprevention' between 2006 and August 2009. Results, A total of 48 studies were retrieved that link 5-ASA chemopreventive properties to five distinct pathways. These include interference with cell cycle progression (12 references), scavenging of reactive oxygen- or nitrogen-derived metabolites (16 references), TNF-,/TGF-ß signalling (11 references), WNT/,-catenin signalling (5 references) and anti-bacterial properties (4 references). Conclusions, In the recent years, a large amount of molecular data has accumulated supporting the notion that 5-ASA biological effects interfere with colorectal cancer development. These molecular pathways are of special interest in the search for 5-ASA's molecular target(s) and development of novel chemopreventive compounds. Aliment Pharmacol Ther,31, 202,209 [source] Mesalazine inhibits the , -catenin signalling pathway acting through the upregulation of ,-protocadherin gene in colo-rectal cancer cellsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010S. PARENTI Summary Background, Several reports indicate that mesalazine (5-aminosalicylic acid, 5-ASA) is a promising candidate for the chemoprevention of colo-rectal cancer because of its ability to reach the purpose avoiding the unwanted side effects usually associated with prolonged administration of nonsteroidal anti-inflammatory drugs. This activity of 5-ASA is probably the consequence of a number of effects determined on colo-rectal cancer cells, consisting of reduced proliferation, increased apoptosis and activation of cell cycle checkpoints and DNA repair processes. A recent observation has suggested that inhibition of ,-catenin signalling could induce these cellular effects. Aim, To characterize better the capacity of 5-ASA to inhibit the ,-catenin signalling pathway. Methods, Genes belonging to the ,-catenin signalling pathway were analysed in colo-rectal cancer cell lines treated with 5-ASA using a combination of laboratory assays that are able to detect their phenotypic expression and functional activity. Results, The results obtained indicated that 5-ASA induces the expression of a protein called ,-protocadherin that belongs to the cadherin superfamily and is able to sequester ,-catenin on the plasmatic membrane of treated cells hampering its function. Conclusion, These findings suggest that ,-protocadherin might be employed as a biological marker to monitor the chemopreventive efficacy of 5-ASA. [source] Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009R. CORINALDESI Summary Background, Intestinal immune infiltration contributes to symptoms in patients with irritable bowel syndrome (IBS). Aim, To assesses the effect of mesalazine (mesalamine) on mucosal immune cells in patients with IBS, through a pilot study. Methods, A randomized, double-blind, placebo-controlled trial in 20 patients with IBS in tertiary care setting. Patients were randomized to receive placebo or 800 mg mesalazine three times daily for 8 weeks. The primary endpoint was a significant reduction in total colonic immune cells on biopsies obtained at the end of treatment compared to baseline. Secondary endpoints included effects on subsets of immune cells, inflammatory mediators and symptom severity. Intention-to-treat analysis was performed. Results, Mesalazine markedly reduced immune cells as compared with placebo (P = 0.0082); this effect was ascribed to a marked inhibition of mast cells (P = 0.0014). Mesalazine significantly increased general well-being (P = 0.038), but had no significant effects on abdominal pain (P = 0.084), bloating (P = 0.177) or bowel habits. No serious drug-related adverse events were reported during the study. Conclusions, Mesalazine is an effective and safe approach to reduce mast cell infiltration and may improve general well-being in patients with IBS. These results support the hypothesis that immune mechanisms represent potential therapeutic targets in IBS. [source] Mesalazine downregulates c-Myc in human colon cancer cells.ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2007A key to its chemopreventive action? Summary Background, Dysplasia and malignant transformation of colonocytes in ulcerative colitis are associated with overexpression of c-Myc and genes regulating cell survival. 5-Aminosalicylates such as mesalazine may reduce the development of colorectal cancer in ulcerative colitis, but the mechanisms of its chemopreventive action are not clear. Aims, To examine whether mesalazine affects the expression of c-Myc in human colon cancer cell lines. Methods, Human colon cancer cells were treated with vehicle or mesalazine (4 mm or 40 mm). We examined: (i) mRNA expression by gene array, (ii) protein expression by Western blotting and immunohistochemistry and (iii) apoptosis by Annexin V labelling. Results, Mesalazine significantly reduced expression of c-Myc mRNA and protein. Conclusions, Mesalazine downregulates gene and protein expression of c-Myc. The apoptotic and growth inhibitory effects of mesalazine are dose-dependent. Expression of c-Myc is significantly reduced by mesalazine 40 mm. [source] Review article: uncomplicated diverticular disease of the colonALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006L. PETRUZZIELLO Summary Diverticular disease of the colon is the fifth most important gastrointestinal disease in terms of direct and indirect healthcare costs in western countries. Uncomplicated diverticular disease is defined as the presence of diverticula in the absence of complications such as perforation, fistula, obstruction and/or bleeding. The distribution of diverticula along the colon varies worldwide being almost always left-sided and directly related to age in western countries and right-sided where diet is rich in fibre. The pathophysiology of diverticular disease is complex and relates to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation, imbalance in colonic microflora and visceral hypersensitivity. Moreover, there can be genetic factors involved in the development of colonic diverticula. The use of non-absorbable antibiotics is the mainstay of therapy in patients with mild to moderate symptoms, and the effect of fibre-supplementation alone does not appear to be significantly different from placebo, although no definite data are available. More recently, alternative treatments have been reported. Mesalazine acts as a local mucosal immunomodulator and has been shown to improve symptoms and prevent recurrence of diverticulitis. In addition, probiotics have also been shown to be beneficial by re-establishing a normal gut microflora. In this study, the current literature on uncomplicated diverticular disease of the colon is reviewed. [source] Systematic review: the use of mesalazine in inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2006R. BERGMAN Summary Background, Mesalazine is among the medications most commonly prescribed by gastroenterologists, having to a large extent superseded sulfasalazine (sulphasalazine). However, there are still a number of aspects regarding its use which provoke debate and controversy. Aim, To provide a systematic assessment of the evidence for the use of mesalazine in ulcerative colitis and Crohn's disease. Methods, References were identified using PubMed database. Additional references were identified with related article searches. Results, Mesalazine has a clear role in the maintenance of remission in ulcerative colitis and management of mild to moderately active disease, although the efficacy of topical preparations or combined topical and oral is clearly superior to oral alone. Evidence that increasing the dose of oral mesalazine improves efficacy is not clear-cut. The benefits of mesalazine in the management of acute Crohn's disease and the maintenance of remission are questionable and alternative treatments are usually more appropriate. Emerging evidence suggests that maintenance mesalazine reduces the risk of neoplastic progression in chronic ulcerative colitis. Compliance with therapy is thus important, as is an understanding of individuals most likely to default on this. Conclusion, Evidence for a beneficial effect of mesalazine is largely confined to the management of ulcerative colitis. [source] 5-aminosalicylic acid release from a new controlled-release mesalazine formulation during gastrointestinal transit in healthy volunteersALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2006M. BRUNNER Summary Background Mesalazine (5-aminosalicylic acid, 5-ASA) containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. A novel formulation with an Eudragit L/S mixture coating has been developed to provide selective release of 5-ASA to the ileo-caecal region and the colon. Aim To determine the release of 5-ASA during the gastrointestinal transit. Methods A single oral dose of mesalazine EC 500 mg gastroresistant tablets (Asamax) was administered to eight healthy male volunteers. Gastrointestinal transit and tablet disintegration were monitored by scintigraphy. 5-ASA release was verified by assessing plasma pharmacokinetics. Results Initial tablet disintegration was observed 5.65 ± 0.86 h after dosing, corresponding to the detection of 5-ASA in plasma. This occurred in the ileo-caecal region in three subjects and the ascending colon in the remaining five. The relative percentage of 5-ASA absorption was more pronounced in the ascending colon (41 ± 27.4%) than the ileo-caecal region (6.6 ± 9.2%). Conclusion This mesalazine EC gastroresistant tablets release locally active 5-ASA specifically in the ileo-caecal region and the ascending colon. [source] 5-Aminosalicylic acid (mesalazine) use in Crohn's disease: A survey of the opinions and practice of Australian gastroenterologistsINFLAMMATORY BOWEL DISEASES, Issue 8 2007Richard B. Gearry MD Abstract Background: The use of 5-aminosalicylate (5-ASA) drugs in Crohn's disease (CD) is controversial, with their continuing apparent widespread use despite high-level evidence indicating marginal benefit at best and international guidelines recommending limited indications. Methods: In order to understand how clinicians translate the evidence base into clinical practice, we surveyed a cross-section of Australian gastroenterologists to determine opinions and prescribing patterns of 5-ASA drugs in CD. Results: In all, 42% of 285 gastroenterologists who were sent a questionnaire by e-mail responded. Five (4%) never use 5-ASA drugs in CD. The drugs are most commonly prescribed for patients with colonic (96%) or ileocolonic (92%) disease location, inflammatory disease behavior (80%), and mild disease activity (97%). The majority (64%) use a dose of 1,3 g/day, but only 6% use over 4.5 g/day. Less than one-half use 5-ASA drugs as maintenance following surgical resection, but most use it for inducing remission alone (70%) or in combination with other drugs (90%), and continue its use for maintenance. Side effects are thought to be infrequent (62%) or rare (20%) and few common side effects are believed to be serious. Respondents estimated that over 90% of patients were nonadherent to prescribed 5-ASA regimens at least 50% of the time. While 84% believed that 5-ASA drugs were effective in CD, only 58% believed that they were cost-effective. Conclusions: In Australia 5-ASA drugs are extensively prescribed for CD at relatively low doses without expectation of patient adherence. Current evidence and guidelines has had little apparent impact on clinical practice. The cost implications are considerable. (Inflamm Bowel Dis 2007) [source] Medical management of left-sided ulcerative colitis and ulcerative proctitis: Critical evaluation of therapeutic trialsINFLAMMATORY BOWEL DISEASES, Issue 10 2006Miguel Regueiro MD Abstract Background: The goal of this work was to critically evaluate the published studies on the treatment of ulcerative proctitis (UP) and left-sided ulcerative colitis (L-UC). The results of this review provided the content for the accompanying treatment guidelines, Clinical Guidelines for the Medical Management of Left-sided Ulcerative Colitis and Ulcerative Proctitis: Summary Statement. Methods: All English language articles published between 1995 and September 2005 were identified through a comprehensive literature search using OVID and PubMed. The quality of the data supporting or rejecting the use of specific therapies was categorized by a data quality grading scale. An "A+" grade was assigned to treatment supported by multiple high-quality randomized controlled trials with consistent results, whereas a "D" grade was given to therapy supported only by expert opinion. The therapeutic efficacy of a treatment was defined by its success in treating UP and L-UC compared with placebo. A medication was ranked as "excellent" if it was specifically studied for UP and L-UC and had consistently positive results compared with placebo or another agent. Quality and efficacy scores were agreed on by author consensus. Results: For the acute treatment of UP or L-UC, the rectally administered corticosteroids and mesalazine (5-ASA), either alone or in combination with oral 5-ASAs, are the most effective therapy: evidence quality, A+; efficacy, excellent. Only rectally administered 5-ASA received an A+/excellent rating for maintenance of remission. Infliximab received an A+ grade for induction and maintenance of remission but only a "good" rating because the studies were performed in all UC, not specifically UP or L-UC. Conclusions: This critical evaluation of treatment provides a "report card" on medications available for the management of patients with UP and L-UC. The guidelines should provide a useful reference and supplement for physicians treating UC patients. [source] Myopericarditis and mitral insufficiency associated with ulcerative colitis treated with mesalazineINFLAMMATORY BOWEL DISEASES, Issue 4 2006Sara García-Morán MD No abstract is available for this article. [source] A new oral delivery system for 5-ASA: Preliminary clinical findings for MMxINFLAMMATORY BOWEL DISEASES, Issue 5 2005Cosimo Prantera MD Abstract Background: Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how the therapy would compare with topical 5-ASA. Methods: Patients received either 1.2 g of 5-ASA MMx three times per day plus placebo enema or 4 g of 5-ASA enema plus placebo tablets for 8 weeks. The primary endpoint was clinical remission (clinical activity index ,4) at 8 weeks. Secondary endpoints were endoscopic and histologic remissions. Results: Seventy-nine patients were enrolled. Clinical remission rates at 4 and 8 weeks were 57.5% and 60.0% for patients treated with MMx and 68.4% and 50.0% for patients randomized to 5-ASA enemas, respectively (95% confidence interval for the difference at 8 weeks, ,12 to +32). Endoscopic remission was achieved by 45.0% of patients on 5-ASA MMx and by 36.8% of those on enema, whereas 15.0% and 8% of patients, respectively, showed histologic remission. Compliance was 97.0% for oral and 87.5% for topical therapy. In the enema group, compliance was 88.0% for the patients in remission and 65.5% for those with active disease. Conclusions: Preliminary studies suggest that similar rates for induction of remission can be expected from 5-ASA enemas and MMx for patients with left-sided ulcerative colitis. [source] Pharmacokinetics of mesalazine pellets in children with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 5 2004Heleen Wiersma MD Abstract Mesalazine is a first-line drug in pediatric inflammatory bowel disease (IBD), and is customarily used to induce and maintain remission in mild to moderate disease. In children, pharmacokinetic data are scarce, and dosage recommendations are largely extrapolated from studies in adults. Aim of the study was to obtain the pharmacokinetic profile of a new mesalazine pellet formulation in children with ulcerative colitis and Crohn's colitis. A single oral dose of 20 mg/kg mesalazine was administered to 13 patients (age 6,16 years). Serial blood and urine sampling for determination of mesalazine and acetylmesalazine was performed before and during 24 hours following ingestion. Maximum plasma concentration of mesalazine (Cmax) was 1332 ng/mL (geometric mean, geometric coefficient of variation [CV]: 0.57), obtained 3.7 hours (tmax; CV: 0.31) after drug administration. Systemic exposure as determined by area under the plasma concentration-time curve (AUC0,, ) was 8712 ng/ml*h (CV: 0.44). Terminal half-life of elimination of mesalazine was 3.5 hours (t1/2; CV: 1.43). This study presents extensive pharmacokinetic data on mesalazine in children with mild-moderately active ulcerative colitis and Crohn's colitis. In comparison with previous experience in adults, pharmacokinetics of mesalazine administered as pellets appear to be similar in both populations. [source] Mesalazine 4 g daily given as prolonged-release granules twice daily and four times daily is at least as effective as prolonged-release tablets four times daily in patients with ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 3 2001Dr. Per G. Farup Abstract Background High doses of mesalazine usually result in an inconvenient dosage schedule and reduced compliance. The goal of this trial was to compare the effects of mesalazine 4 g daily given as prolonged-release granules in packets of 1 g with that of prolonged-release tablets of 0.5 g. Methods Two hundred twenty-seven patients with mild-to-moderate ulcerative colitis were randomized to treatment with two packets twice daily (Gr-b.i.d.), 1 packet four times daily (Gr-q.i.d.) or 2 tablets four times daily (Ta-q.i.d.) for 8 weeks. A disease activity index (ulcerative colitis disease activity index; UC-DAI) was calculated, and the granules were defined as noninferior to the tablets if the lower limit of the 95% CI for the differences was more than ,1 UC-DAI score unit. Results Noninferiority of the granules compared with the tablets was demonstrated. The mean improvement in the UC-DAI in the treatment groups Gr-b.i.d., Gr-q.i.d., and Ta-q.i.d. were 3.2, 2.9, and 2.4, respectively; the proportion of complete responders in the three groups 39%, 37%, and 31%, respectively. There were no differences in side effects. Conclusion Mesalazine 4 g daily given as prolonged-release granules twice and four times daily is at least as effective as prolonged-release tablets four times daily in patients with mild to moderate ulcerative colitis. The patients preferred the twice daily dosing. [source] Mesalazine with or without cholestyramine in the treatment of microscopic colitis: Randomized controlled trialJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2007Carlo Calabrese Abstract Background:, Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory diseases of the colon with a benign and sometimes relapsing course. Frequency among patients with chronic diarrhea and normal looking colonoscopy is around 10,15%. To date, treatment of CC and LC is not well defined. Data about these conditions are mostly derived from retrospective studies. The aim of the present study was to evaluate the response to treatment and the clinical course of CC and LC in a large group of patients prospectively diagnosed. Methods and Results:, A total of 819 patients underwent a colonoscopy because of chronic watery diarrhea and among them we found 41 patients with LC and 23 with CC. These patients were later randomized and assigned to treatment with mesalazine or mesalazine + cholestyramine for 6 months. Fifty-four patients (84.37%) had resolved diarrhea in less than 2 weeks. After 6 months a colonoscopy with biopsies was repeated. Clinical and histological remission was achieved in 85.36% of patients with LC and in 91.3% with CC, with a better result in patients with CC treated with mesalazine + cholestyramine. During a mean period of 44.9 months, 13% of patients relapsed; four with LC and three with CC. They were retreated for another 6 months. At the end of this period one patient with CC was still symptomatic and persistence of CC was confirmed at histology. Conclusions:, Treatment with mesalazine seems to be an effective therapeutic option for LC to date, while mesalazine + cholestyramine seems to be more useful in the treatment of CC. [source] Clinical trial: once-daily mesalamine granules for maintenance of remission of ulcerative colitis , a 6-month placebo-controlled trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010G. R. Lichtenstein Aliment Pharmacol Ther 2010; 32: 990,999 Summary Background, Ulcerative colitis (UC) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder. Aim, To evaluate once-daily mesalamine (mesalazine) granules (MG) for maintenance of remission of UC. Methods, Randomized, double-blind, placebo-controlled trial of patients (n = 209 MG, n = 96 placebo) with UC in remission [revised Sutherland Disease Activity Index (SDAI) rectal bleeding = 0, mucosal appearance <2] who took MG 1.5 g or placebo once-daily for up to 6 months. Primary efficacy endpoint: the percentage of patients who remained relapse-free at month 6/end of treatment. Relapse was defined as SDAI rectal bleeding score ,1 and a mucosal appearance score ,2, a UC flare, or initiation of medication to treat a UC flare. Results, The percentage of relapse-free patients at month 6/end of treatment was higher with MG than placebo (78.9% vs. 58.3%, P < 0.001) in the intent-to-treat analysis. Significant differences (P , 0.025) favouring MG were observed for most secondary endpoints including improvement in rectal bleeding, physician's disease activity rating, stool frequency, the SDAI at month 6/end of treatment, patients classified as a treatment success and relapse-free duration. The incidence of adverse events was similar between groups. Conclusions, Once-daily mesalamine (mesalazine) was effective in maintaining remission of UC for 6 months. [source] Systematic review: molecular chemoprevention of colorectal malignancy by mesalazineALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010A. LYAKHOVICH Summary Background, Mesalazine (mesalamine) (5-ASA) is considered an anti-inflammatory drug for the treatment of inflammatory bowel disease. It is well tolerated by most patients and induces mucosal healing specifically in ulcerative colitis. Besides its anti-inflammatory properties, 5-ASA has been studied for cancer inhibitory activities as it seems to reduce colorectal cancer incidence in patients using this drug for long periods of time. However, detailed molecular mechanisms of drug action are vague. Aims, To evaluate known molecular mechanisms of 5-ASA on chemoprevention of colorectal malignancy. Methods, Systematic review with search terms ,5 aminosalicylic acid, mesalazine, 5-ASA, mesalazine, molecular mechanisms, chemoprevention' between 2006 and August 2009. Results, A total of 48 studies were retrieved that link 5-ASA chemopreventive properties to five distinct pathways. These include interference with cell cycle progression (12 references), scavenging of reactive oxygen- or nitrogen-derived metabolites (16 references), TNF-,/TGF-ß signalling (11 references), WNT/,-catenin signalling (5 references) and anti-bacterial properties (4 references). Conclusions, In the recent years, a large amount of molecular data has accumulated supporting the notion that 5-ASA biological effects interfere with colorectal cancer development. These molecular pathways are of special interest in the search for 5-ASA's molecular target(s) and development of novel chemopreventive compounds. Aliment Pharmacol Ther,31, 202,209 [source] Mesalazine inhibits the , -catenin signalling pathway acting through the upregulation of ,-protocadherin gene in colo-rectal cancer cellsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010S. PARENTI Summary Background, Several reports indicate that mesalazine (5-aminosalicylic acid, 5-ASA) is a promising candidate for the chemoprevention of colo-rectal cancer because of its ability to reach the purpose avoiding the unwanted side effects usually associated with prolonged administration of nonsteroidal anti-inflammatory drugs. This activity of 5-ASA is probably the consequence of a number of effects determined on colo-rectal cancer cells, consisting of reduced proliferation, increased apoptosis and activation of cell cycle checkpoints and DNA repair processes. A recent observation has suggested that inhibition of ,-catenin signalling could induce these cellular effects. Aim, To characterize better the capacity of 5-ASA to inhibit the ,-catenin signalling pathway. Methods, Genes belonging to the ,-catenin signalling pathway were analysed in colo-rectal cancer cell lines treated with 5-ASA using a combination of laboratory assays that are able to detect their phenotypic expression and functional activity. Results, The results obtained indicated that 5-ASA induces the expression of a protein called ,-protocadherin that belongs to the cadherin superfamily and is able to sequester ,-catenin on the plasmatic membrane of treated cells hampering its function. Conclusion, These findings suggest that ,-protocadherin might be employed as a biological marker to monitor the chemopreventive efficacy of 5-ASA. [source] Review article: the current and evolving treatment of colonic diverticular diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009A. TURSI Summary Background, Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis and consequently diverticular disease. Diverticular disease can be associated with numerous debilitating abdominal and gastrointestinal symptoms (including pain, bloating, nausea, constipation and diarrhoea). Aims, To review the state of treatment for diverticular disease and its complications, and briefly discuss potential future therapies. Methods, PubMed and recent conference abstracts were searched for articles describing the treatment of diverticular disease. Results, Many physicians will recommend alterations to lifestyle and increasing fibre consumption. Empirical antibiotics remain the mainstay of therapy for patients with diverticular disease and rifaximin seems to be the best choice. In severe or relapsing disease, surgical intervention is often the only remaining treatment option. Although novel treatment options are yet to become available, the addition of therapies based on mesalazine (mesalamine) and probiotics may enhance treatment efficacy. Conclusions, Data suggest that diverticular disease may share many of the hallmarks of other, better-characterized inflammatory bowel diseases; however, treatment options for patients with diverticular disease are scarce, revolving around antibiotic treatment and surgery. There is a need for a better understanding of the fundamental mechanisms of diverticular disease to design treatment regimens accordingly. [source] In vivo effects of mesalazine or E. coli Nissle 1917 on microsatellite instability in ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009A. GOEL Summary Background, Microsatellite instability (MSI) occurs in chronically inflamed colorectal tissue and may evolve to colitis-associated cancer. In vitro data suggest that mesalazine (5-ASA) improves MSI. Aim, To analyse the changes in MSI in 156 distal colonic biopsies of 39 patients with ulcerative colitis that had been treated within a randomized, double-blind trial comparing 5-ASA with E. coli Nissle (EcN). Methods, Two biopsies had been collected before and after 1 year of treatment. MSI testing was performed using a panel of eight markers, including 3 dinucleotide and 5 mononucleotide repeats. Results, No MSI was observed with any of the mono-repeats, and among dinucleotide repeats, only D5S346 (maps to APC) and D17S250 (p53) were consistently informative. Overall, 31/156 (20%) biopsies displayed MSI. After 1 year, 3/11 patients displayed MSI improvement [change to microsatellite stability (MSS); 1 on 5-ASA, 2 on EcN] at D5S346 and 4/11 showed MSI worsening (change from MSS to MSI; all 5-ASA). For D17S250, the corresponding data were for 3/9 patients (2 on 5-ASA, 1 on EcN) and 2/9 (both on 5-ASA), respectively. Conclusions, In the set of biopsies taken from patients treated with 1.5 g 5-ASA for 1 year, there was no improvement in the prevalence of MSI in the distal colon. [source] Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009R. CORINALDESI Summary Background, Intestinal immune infiltration contributes to symptoms in patients with irritable bowel syndrome (IBS). Aim, To assesses the effect of mesalazine (mesalamine) on mucosal immune cells in patients with IBS, through a pilot study. Methods, A randomized, double-blind, placebo-controlled trial in 20 patients with IBS in tertiary care setting. Patients were randomized to receive placebo or 800 mg mesalazine three times daily for 8 weeks. The primary endpoint was a significant reduction in total colonic immune cells on biopsies obtained at the end of treatment compared to baseline. Secondary endpoints included effects on subsets of immune cells, inflammatory mediators and symptom severity. Intention-to-treat analysis was performed. Results, Mesalazine markedly reduced immune cells as compared with placebo (P = 0.0082); this effect was ascribed to a marked inhibition of mast cells (P = 0.0014). Mesalazine significantly increased general well-being (P = 0.038), but had no significant effects on abdominal pain (P = 0.084), bloating (P = 0.177) or bowel habits. No serious drug-related adverse events were reported during the study. Conclusions, Mesalazine is an effective and safe approach to reduce mast cell infiltration and may improve general well-being in patients with IBS. These results support the hypothesis that immune mechanisms represent potential therapeutic targets in IBS. [source] Systematic review: does concurrent therapy with 5-ASA and immunomodulators in inflammatory bowel disease improve outcomes?ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009J. M. ANDREWS Summary Background, With greater use of immunomodulators in inflammatory bowel disease (IBD), it is uncertain whether concurrent therapy with both 5-aminosalicylic acid [5-ASA, mesalazine (mesalamine)] and an immunomodulator is necessary. Aim, To determine whether concurrent therapy with both 5-ASA and immunomodulator(s) improves outcomes in IBD. Methods, Systematic review with search terms ,azathioprine, 6-mercaptopurine, thiopurine(s), 5 aminosalicylic acid, mesalazine, inflammatory bowel disease, ulcerative colitis, Crohn's disease, immunosuppressant(s), immunomodulator and methotrexate' in November 2007 to identify clinical trials on concurrent 5-ASA and immunomodulator therapy. Results, Two small controlled studies were found. Neither showed a benefit on disease control beyond immunomodulator monotherapy. Potential pharmacological interactions exist between 5-ASA and thiopurines. Whilst circumstantial, epidemiological and laboratory evidence suggests that 5-ASA may assist colorectal cancer (CRC) chemoprevention, it may simply be via anti-inflammatory effects. With changes in practice, ethical issues and the long lead-time needed to demonstrate or disprove an effect, no clinical studies can/will directly answer this. The costs of avoiding one CRC in IBD may be as low as 153 times the annual cost of 5-ASA therapy. Conclusions, It is unclear whether concurrent 5-ASA and immunomodulator therapy improves outcomes of disease control, drug toxicity or compliance. Concurrent therapy of 5-ASA and immunomodulators may decrease CRC risk at ,acceptable' cost. [source] Review article: medication non-adherence in ulcerative colitis , strategies to improve adherence with mesalazine and other maintenance therapiesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2008A. B. HAWTHORNE Summary Background, Significant number of patients with ulcerative colitis (UC) fail to comply with treatment. Aims, To review issues surrounding medication non-adherence in inflammatory bowel disease (IBD), including the clinical and health service implications in the UK, and discuss strategies for optimizing medication adherence. Methods, Articles cited were identified via a PubMed search, utilizing the words IBD, adherence, compliance, medication and UC. Results, Medication non-adherence is multifactorial involving factors other than dosing frequency. Male gender (OR: 2.06), new patient status (OR: 2.14), work and travel pressures (OR: 4.9) and shorter disease duration (OR: 2.1), among others are proven predictors of non-adherence in UC. These indicators can identify ,at-risk' patients and allow an individually tailored treatment approach to be introduced that optimizes medication adherence. A collaborative relationship between physician and patient is important; several strategies for improving adherence have been proven effective including open dialogue that takes into consideration the patient's health beliefs and concerns, providing educational (e.g. verbal/written information, self-management programmes) and behavioural interventions (e.g. calendar blister packs, cues/reminders). Conclusions, Educational and behavioural interventions tailored to individual patients can optimize medication adherence. Additional studies combining educational and behavioural interventions may provide further strategies for improving medication adherence rates in UC. [source] Review article: increasing the dose of oral mesalazine therapy for active ulcerative colitis does not improve remission ratesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2007A. V. SAFDI Summary Background, Oral mesalazine (mesalamine, 5-aminosalicylic acid) formulations are effective in the treatment of active ulcerative colitis. All formulations contain the same active drug but differ with regard to mechanisms to deliver the drug to the colon. Patients who fail to respond to initial therapy are often administered higher doses of the same formulation. Aim, To review published trials of oral mesalazine formulations in treating active ulcerative colitis and to examine the effect of dose escalation on remission rates. Results, Increasing the doses of oral mesalazine formulations does not result in higher remission rates, although increasing the doses of some formulations has been effective in increasing symptomatic improvement and/or response to treatment. Conclusions, Because oral mesalazine formulations do not demonstrate a significant dose response with regard to induction of remission of active ulcerative colitis, simple dose escalation may not be the most effective course for patients who fail to respond to initial mesalazine treatment. [source] Mesalazine downregulates c-Myc in human colon cancer cells.ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2007A key to its chemopreventive action? Summary Background, Dysplasia and malignant transformation of colonocytes in ulcerative colitis are associated with overexpression of c-Myc and genes regulating cell survival. 5-Aminosalicylates such as mesalazine may reduce the development of colorectal cancer in ulcerative colitis, but the mechanisms of its chemopreventive action are not clear. Aims, To examine whether mesalazine affects the expression of c-Myc in human colon cancer cell lines. Methods, Human colon cancer cells were treated with vehicle or mesalazine (4 mm or 40 mm). We examined: (i) mRNA expression by gene array, (ii) protein expression by Western blotting and immunohistochemistry and (iii) apoptosis by Annexin V labelling. Results, Mesalazine significantly reduced expression of c-Myc mRNA and protein. Conclusions, Mesalazine downregulates gene and protein expression of c-Myc. The apoptotic and growth inhibitory effects of mesalazine are dose-dependent. Expression of c-Myc is significantly reduced by mesalazine 40 mm. [source] Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2006M. A. ZOCCO Summary Background Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder. Aim To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis. Patients and methods 187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 × 109 viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission. Results Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse-free time (P < 0.05). Conclusions Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients. [source] Systematic review: the use of mesalazine in inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2006R. BERGMAN Summary Background, Mesalazine is among the medications most commonly prescribed by gastroenterologists, having to a large extent superseded sulfasalazine (sulphasalazine). However, there are still a number of aspects regarding its use which provoke debate and controversy. Aim, To provide a systematic assessment of the evidence for the use of mesalazine in ulcerative colitis and Crohn's disease. Methods, References were identified using PubMed database. Additional references were identified with related article searches. Results, Mesalazine has a clear role in the maintenance of remission in ulcerative colitis and management of mild to moderately active disease, although the efficacy of topical preparations or combined topical and oral is clearly superior to oral alone. Evidence that increasing the dose of oral mesalazine improves efficacy is not clear-cut. The benefits of mesalazine in the management of acute Crohn's disease and the maintenance of remission are questionable and alternative treatments are usually more appropriate. Emerging evidence suggests that maintenance mesalazine reduces the risk of neoplastic progression in chronic ulcerative colitis. Compliance with therapy is thus important, as is an understanding of individuals most likely to default on this. Conclusion, Evidence for a beneficial effect of mesalazine is largely confined to the management of ulcerative colitis. [source] Comparison of the efficacy and safety of Eudragit-L-coated mesalazine tablets with ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2006P. R. GIBSON Summary Background, There are no comparative studies of coated mesalazine. Aim, To compare the efficacy and tolerability of Eudragit-L- and ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitis. Methods, A double-blind, double-dummy, randomized parallel group trial was performed across 18 centres in Australia, and 20 in Eastern Europe. Patients were treated with 3 g mesalazine for 8 weeks with the primary efficacy end point being clinical remission. Results, Of 215 patients, 69% achieved clinical remission in both treatment groups (P < 0.001; chi-square test) with no differences in frequency of adverse events. In the Australian cohort (n = 63), the Eudragit-L group had a higher remission rate (73% vs. 36%) and responded 13 days faster, compared with those in the European group (67% vs. 84%, and 2 days respectively). No clear reasons for differences in treatment responses were identified. Conclusions, Eudragit-L and ethylcellulose-coated mesalazine tablets are well tolerated and equally effective in achieving remission in mild-moderately active ulcerative colitis over 8 weeks. [source] | ||||||||||