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Drugs 2007* Mesalazine appears to act locally on the mucosa of the colon and reduces the inflammation associated with ulcerative colitis. * Following oral administration, the... (Review)
Review
* Mesalazine appears to act locally on the mucosa of the colon and reduces the inflammation associated with ulcerative colitis. * Following oral administration, the majority (*78%) of a dose of delayed-release Multi Matrix System (MMX) mesalazine passes unabsorbed through the upper gastrointestinal tract to reach and traverse the entire length of the colon. * In a well designed phase III trial in patients with active, mild to moderate ulcerative colitis (n = 262), significantly (p < 0.01) more MMX mesalazine 2.4 (34%) or 4.8 g/day (29%) recipients than placebo recipients (13%) achieved clinical and endoscopic remission after 8 weeks of treatment.* In a second phase III trial (n = 341), clinical and endoscopic remission rates with MMX mesalazine 2.4 (40.5%) and 4.8 g/day (41.2%) were significantly (p < 0.01) greater than with placebo (22.1%) after 8 weeks, while the remission rate with non-MMX delayed-release mesalazine (Asacol) [32.6%] did not differ from placebo.* Overall, MMX mesalazine was generally well tolerated in controlled clinical trials, with a similar incidence of treatment-emergent adverse events in placebo (66%) and MMX mesalazine (56%) recipients in a pooled analysis; most adverse events were of mild or moderate severity. Two of 434 MMX mesalazine recipients experienced serious adverse events that were considered treatment related (pancreatitis caused by mesalazine sensitivity).
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Delayed-Action Preparations; Drug Tolerance; Humans; Mesalamine; Remission Induction; Sensitivity and Specificity; Treatment Outcome
PubMed: 18034594
DOI: 10.2165/00003495-200767170-00010 -
Scandinavian Journal of... 2002Sulfasalazine, consisting of 5-aminosalicylic acid bound to sulfapyridine by a diazo bond, was first used for treatment of ulcerative colitis in the early 1940s and... (Review)
Review
BACKGROUND
Sulfasalazine, consisting of 5-aminosalicylic acid bound to sulfapyridine by a diazo bond, was first used for treatment of ulcerative colitis in the early 1940s and later found effective in placebo-controlled trials for acute disease and for long-term maintenance of remission. Later studies found that the active moiety is 5-ASA (mesalazine, mesalamine) and the sulfapyridine moiety acts as a carrier molecule but causes many of the symptomatic adverse reactions.
METHODS
Review of the literature.
RESULTS
The finding that 5-ASA in the active motility led to the development of mesalazine prodrugs, olsalazine (Dipentum) and balsalazide (Colazide, Colazal), and targeted release mesalazine preparations, such as Asacol, Pentasa, and Salofalk, as well as enemas and suppository preparations for distal disease. Most patients with adverse effects from sulfasalazine will tolerate mesalazine. Mesalazine has been shown equivalent or superior to sulfasalazine, and superior to placebo, with a dose-response benefit, in inducing remission of acute disease. and comparable to sulfasalazine and superior to placebo for long-term maintenance of remission. Better tolerance of mesalazine and the ability to use higher doses favor its use in patients intolerant of sulfasalazine and in patients failing to respond to usual doses of sulfasalazine. Adverse effects from mesalazine are uncommon, but include idiosyncratic worsening of the colitis symptoms and renal toxicity. Mesalazine is safe to use during pregnancy and for nursing mothers. As maintenance therapy, mesalazine may reduce the risk of developing colorectal carcinoma.
CONCLUSION
Mesalazine represents effective and well-tolerated first-line therapy for mildly to moderately acute disease as well as for the long-term maintenance treatment in the patient with ulcerative colitis.
Topics: Acute Disease; Administration, Oral; Administration, Rectal; Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Enema; Humans; Mesalamine; Phenylhydrazines; Prodrugs; Sulfasalazine; Time Factors
PubMed: 12408503
DOI: 10.1080/003655202320621445 -
World Journal of Gastroenterology Apr 20095-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azobond...
5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azobond pro-drugs, as well as delayed- and controlled-release forms of mesalazine. However, poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine, including the unique multi-matrix delivery system and mesalazine granules, were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice. This editorial summarizes the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Colitis, Ulcerative; Drug Administration Schedule; Humans; Medication Adherence; Mesalamine; Patient Compliance; Placebos; Remission Induction; Treatment Outcome
PubMed: 19370774
DOI: 10.3748/wjg.15.1799 -
Alimentary Pharmacology & Therapeutics Jun 2007To evaluate the effectiveness of pH 6-/pH 7-dependent and controlled-release mesalazines in maintaining medically and surgically induced Crohn's disease remission. (Review)
Review
AIM
To evaluate the effectiveness of pH 6-/pH 7-dependent and controlled-release mesalazines in maintaining medically and surgically induced Crohn's disease remission.
METHODS
A systematic search identified 13 randomized controlled trials (RCTs). The rate of symptomatic relapse (Crohn's disease activity index >150, or an increase in baseline by at least 60-100 points) was extracted from each randomized controlled trial. Pooled odds ratios (OR), the number needed to treat (NNT), and percentage therapeutic benefit (absolute risk reduction) were calculated.
RESULTS
Treatment with pH 7-dependent mesalazine significantly reduced the risk of relapse in patients with either surgically [OR 0.28; 95% confidence interval (CI) 0.12-0.65; P = 0.0032] or medically induced remission (OR 0.38; 95% CI 0.17-0.85; P = 0.0113). However, treatment with controlled-release mesalazine and pH 6-dependent mesalazine failed to show any significant advantage over placebo. The NNT to maintain surgically or medically induced remission was lowest for pH 7-dependent mesalazine (NNT = 4 and 5, respectively; NNT = 15 and 16 for controlled-release mesalazine and NNT = 11 and 23 for pH 6-dependent mesalazine). Therapeutic benefit was highest for pH 7-dependent mesalazine (surgical = 30.6%, medical = 22.8%). This compared with 6.9% (surgical) and 6.4% (medical) for controlled-release mesalazine, and 9.8% and 4.4%, respectively, for pH 6-dependent mesalazine.
CONCLUSION
Further trials of pH 7-dependent mesalazine formulations are warranted in the maintenance of remission in Crohn's disease.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Crohn Disease; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Evaluation; Humans; Mesalamine; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Treatment Outcome
PubMed: 17539978
DOI: 10.1111/j.1365-2036.2007.03324.x -
Alimentary Pharmacology & Therapeutics Mar 2009With greater use of immunomodulators in inflammatory bowel disease (IBD), it is uncertain whether concurrent therapy with both 5-aminosalicylic acid [5-ASA, mesalazine... (Review)
Review
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.
Topics: Aminosalicylic Acids; Drug Therapy, Combination; Humans; Immunologic Factors; Inflammatory Bowel Diseases; Mesalamine; Treatment Outcome
PubMed: 19077129
DOI: 10.1111/j.1365-2036.2008.03915.x -
Medizinische Klinik (Munich, Germany :... Feb 1999Sulfasalazine (SASP), since 60 years standard in the treatment of ulcerative colitis, is a double molecule where 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) are... (Comparative Study)
Comparative Study Review
Sulfasalazine (SASP), since 60 years standard in the treatment of ulcerative colitis, is a double molecule where 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) are linked together by an azobond. Bacterial splitting of SASP within the colon allows delivery of 5-ASA for its topical action (prodrug system). To target 5-ASA without the less tolerable SP down to the lower intestine new prodrugs have been developed and, in addition, mesalazine is offered which contains 5-ASA prepared as a delayed release preparation. A clinical comparison (metaanalysis) tended towards superiority of the new prodrugs and mesalazine over SASP for inducing remission, while SASP was more effective in maintaining remission. Only few studies exist comparing the efficacy of the new drugs and mesalazine. To date a slight superiority of the new prodrugs is implied. With the exception of SASP safety profiles do not significantly differ between the different drugs containing 5-ASA.
Topics: Clinical Trials as Topic; Colitis, Ulcerative; Delayed-Action Preparations; Drug Delivery Systems; Humans; Mesalamine; Treatment Outcome
PubMed: 10194945
DOI: 10.1007/BF03042030 -
Alimentary Pharmacology & Therapeutics Jan 20005-Aminosalicylic acid (5-ASA) has replaced sulphasalazine as first line therapy for mild to moderately active inflammatory bowel disease and is widely used. A number of... (Review)
Review
5-Aminosalicylic acid (5-ASA) has replaced sulphasalazine as first line therapy for mild to moderately active inflammatory bowel disease and is widely used. A number of reports have linked oral 5-ASA therapy to chronic tubulo-interstitial nephritis and this relationship is now well established. Despite increasing recognition of the potential for this serious adverse event, guidelines for monitoring renal function in patients prescribed 5-ASA preparations are not widely employed. Whilst the incidence of this adverse event in the population of patients with inflammatory bowel disease treated with mesalazine is low, the morbidity in an affected individual is high with some cases progressing to end-stage renal disease. Routine monitoring of renal function is simple and inexpensive and could prevent this outcome. Based on the available data, serum creatinine should be estimated prior to commencing treatment, monthly for the first 3 months, 3-monthly for the next 9 months, 6-monthly thereafter and annually after 5 years of treatment.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Inflammatory Bowel Diseases; Mesalamine; Nephritis, Interstitial
PubMed: 10632639
DOI: 10.1046/j.1365-2036.2000.00683.x -
Journal of Clinical Gastroenterology Oct 2016Symptomatic uncomplicated diverticular disease (SUDD) is a common gastrointestinal disease, because it affects about one fourth of the patient harboring colonic... (Review)
Review
Mesalazine for the Treatment of Symptomatic Uncomplicated Diverticular Disease of the Colon and for Primary Prevention of Diverticulitis: A Systematic Review of Randomized Clinical Trials.
BACKGROUND
Symptomatic uncomplicated diverticular disease (SUDD) is a common gastrointestinal disease, because it affects about one fourth of the patient harboring colonic diverticula.
GOAL
To assess the effectiveness of mesalazine in improving symptoms (namely abdominal pain) and in preventing diverticulitis occurrence in patients with SUDD.
STUDY
Only randomized clinical trials (irrespective of language, blinding, or publication status) that compared mesalazine with placebo or any other therapy in SUDD were evaluated. The selected endpoints were symptom relief and diverticulitis occurrence at maximal follow-up. Absolute risk reduction (ARR, with 95% confidence interval) and the number needed to treat were used as measures of the therapeutic effect.
RESULTS
Six randomized clinical trials enrolled 1021 patients: 526 patients were treated with mesalazine and 495 with placebo or other therapies. Symptom relief with mesalazine was always larger than that with placebo and other therapies. However, absolute risk reduction was significant only when mesalazine was compared with placebo, a high-fiber diet, and low-dose rifaximin. The incidence of diverticulitis with mesalazine was lower than that observed with placebo and other treatments, being significant only when compared with placebo.
CONCLUSIONS
Mesalazine is effective in achieving symptom relief and primary prevention of diverticulitis in patients with SUDD.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diverticulitis, Colonic; Diverticulosis, Colonic; Female; Humans; Male; Mesalamine; Middle Aged; Primary Prevention; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27622370
DOI: 10.1097/MCG.0000000000000669 -
Gastroenterology Apr 2010The practice of dosing mesalamines in divided doses for the treatment of ulcerative colitis (UC) began with sulfasalazine and was driven by sulfapyridine toxicity. This... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
The practice of dosing mesalamines in divided doses for the treatment of ulcerative colitis (UC) began with sulfasalazine and was driven by sulfapyridine toxicity. This convention and the assumption that dosing multiple times a day is necessary to treat UC had not been challenged until recently. This study was conducted to determine the efficacy and safety of once-daily dosing of delayed-release mesalamine (Asacol 400-mg tablets) compared with twice-daily dosing for maintaining remission in UC patients.
METHODS
A multicenter, randomized, investigator-blinded, 12-month, active-control trial was conducted to assess the noninferiority of delayed-release mesalamine 1.6-2.4 g/day administered once daily compared with twice daily in patients with mild-to-moderate UC currently in clinical remission. The primary end point was maintenance of clinical remission at month 6.
RESULTS
A total of 1023 patients were randomized and dosed. The primary objective of noninferiority was met. At month 6, 90.5% of patients receiving once-daily dosing had maintained clinical remission, compared with 91.8% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -2.3 to 4.9). At month 12, 85.4% of patients receiving once-daily dosing had maintained clinical remission, compared with 85.4% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -4.6 to 4.7). Both regimens had low rates of withdrawals as a result of adverse events and serious adverse events.
CONCLUSIONS
Once-daily dosing of delayed-release mesalamine at doses of 1.6-2.4 g/day was shown to be as effective as twice-daily dosing for maintenance of clinical remission in patients with UC.
Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Delayed-Action Preparations; Drug Administration Schedule; Female; Humans; Male; Mesalamine; Middle Aged
PubMed: 20064514
DOI: 10.1053/j.gastro.2009.12.054 -
Revista Espanola de Enfermedades... Aug 2001
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Male; Mesalamine; Middle Aged; Nephritis, Interstitial
PubMed: 11692787
DOI: No ID Found