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Pharmacological Research 20085-Aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azo-bond... (Review)
Review
5-Aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azo-bond pro-drugs such as sulfasalazine, olsalazine and balsalazide, and delayed- and controlled-release forms of mesalazine. In addition, the effectiveness of oral therapy relies on good compliance, which may be adversely affected by frequent daily dosing and a large number of tablets. Furthermore, poor adherence 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 low pill burden and may contribute to increased long-term compliance and treatment success in clinical practice and might potentially further contribute to a decline in the risk for UC-associated colon cancers. In this systematic review, the authors summarize 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; Chemistry, Pharmaceutical; Colitis, Ulcerative; Humans; Mesalamine; Patient Compliance
PubMed: 18801439
DOI: 10.1016/j.phrs.2008.08.003 -
Expert Review of Gastroenterology &... Jan 2017Ulcerative colitis (uc) is a chronic condition and for the vast majority of patients, life-long treatment is required. low adherence to therapy is an emerging issue.... (Review)
Review
Ulcerative colitis (uc) is a chronic condition and for the vast majority of patients, life-long treatment is required. low adherence to therapy is an emerging issue. since low adherence is associated with poor clinical outcomes and increased costs, it is becoming crucial to identify strategies in order to improve it. Areas covered: We performed literature searches in PubMed using the terms 'adherence', 'mesalamine', 'budesonide MMX', 'MMX technology' in combination with 'ulcerative colitis'. Firstly, we present the key-concepts of therapy for UC and discuss the problem of the adherence and how to measure it. Then, we provide data on the extent of the problem and the causes and consequences from clinical and economic point of views. Finally, we focus on treatment-related variables associated with non-adherence and treatment-related strategies to improve adherence, paying particular attention to Multi Matrix system (MMX) technology applied to mesalazine and budesonide. Expert commentary: The pharmaceutical industry and scientific community are making efforts to simplify treatments for UC. MMX technology, which allows a reduction in the number of pills to be taken and daily administrations, may facilitate adherence to treatment and carry further clinical benefits.
Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Therapy, Combination; Gastrointestinal Agents; Humans; Medication Adherence; Mesalamine; Polymers; Remission Induction; Treatment Outcome
PubMed: 27805459
DOI: 10.1080/17474124.2017.1256200 -
European Journal of Pharmaceutics and... Oct 2021Inflammatory bowel disease incidence has been constantly rising for the past few decades. Current therapies attempt to mitigate its symptoms since no cure is... (Review)
Review
Inflammatory bowel disease incidence has been constantly rising for the past few decades. Current therapies attempt to mitigate its symptoms since no cure is established. The most commonly prescribed drug for these patients is 5-aminosalicylic acid (5-ASA). Due to the low rate and seriousness of side effects compared to other therapies, 5-ASA is still largely prescribed in many stages of inflammatory bowel disease, including scenarios where evidence suggests low effectiveness. Although commercialized formulations have come a long way in improving pharmacokinetics, it is still necessary to design and develop novel delivery systems capable of increasing effectiveness at different stages of the disease. In particular, micro- and nano-sized particles might be the key to its success in Crohn's disease and in more serious disease stages. This review provides an overview on the clinical significance of 5-ASA formulations, its limitations, challenges, and the most recent micro- and nanoparticle delivery systems being designed for its controlled release. Emergent alternatives for 5-ASA are also discussed, as well as the future prospects for its application in inflammatory bowel disease therapies.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Delayed-Action Preparations; Drug Delivery Systems; Humans; Inflammatory Bowel Diseases; Mesalamine; Microspheres; Nanoparticles; Particle Size
PubMed: 34329709
DOI: 10.1016/j.ejpb.2021.07.014 -
World Journal of Gastroenterology Mar 2009Data from both basic research and clinical experience continue to suggest that mesalamines and thiopurines are effective and efficient for the maintenance of remission... (Review)
Review
Data from both basic research and clinical experience continue to suggest that mesalamines and thiopurines are effective and efficient for the maintenance of remission of inflammatory bowel diseases. Several decades following the formalization of their indications, attention on these two drugs has been fostered by recent achievements. Demonstration of the ability of mesalamine to activate a colonocyte differentiation factor has shed light on its chemopreventive effects on colorectal cancer; in addition to their anti-proliferative efficacy, thiopurines have been shown to be specific regulators of apoptosis. The two drugs are often co-administered in clinical practice. Recent advancements have shown that mesalamines exert a positive synergism in this context, insofar as they can inhibit side-methylation of thiopurines and hasten the function of the main immunosuppressive pathways. Considering that up to 40% of patients cannot tolerate thiopurines, such renovated targets have stimulated efforts to improve compliance by research on the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes of thiopurine metabolism, and the uncovering of synergistic drug interactions, such as that with allopurinol, are just two of the results of such efforts. Interaction between basic research and clinical practice has continued to inform indications and refine the prescriptions of mesalamines and thiopurines; these have not been restrained (they have been implemented in some cases) by the advent of the novel biological molecules with anti-cytokine activity.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Crohn Disease; Drug Synergism; Humans; Inflammatory Bowel Diseases; Mesalamine; Prescription Drugs; Purines; Sulfhydryl Compounds
PubMed: 19322913
DOI: 10.3748/wjg.15.1420 -
Alimentary Pharmacology & Therapeutics May 2011The use of topical therapy in the treatment of ulcerative colitis has declined in recent years despite evidence of good efficacy. (Comparative Study)
Comparative Study Review
BACKGROUND
The use of topical therapy in the treatment of ulcerative colitis has declined in recent years despite evidence of good efficacy.
AIMS
To review US prescription trends for 5-aminosalicylic acid (5-ASA) since the US approval of Asacol extended-release oral mesalazine (mesalamine) in 1992; to estimate the optimal level of 5-ASA exposure in the distal colon; to determine factors influencing distal colonic exposures; and to compare the effectiveness of different 5-ASA formulations (oral, topical suspension, foam, suppositories) in clinical trials.
METHODS
Review of clinical trials, physiologic studies and prescription trends of various mesalazine formulations for treatment of distal ulcerative colitis.
RESULTS
Between 1992 and 2009, prescriptions for oral mesalazine increased sixfold, whereas topical suspensions declined by 10%. In clinical trials, topical therapy resulted in higher remission and clinical response rates than oral therapy, with trends to earlier improvement. The mucosal concentrations of 5-ASA achieved by topical agents in the distal colon were up to 200-fold higher than those achieved by oral administration alone. Despite active colitis, over 40% of a topically administered 4 g 5-ASA suspension (equal to 1.6 g) reached the sigmoid colon. This likely represents a therapeutic exposure of 5-ASA. Although topical therapies are less convenient than oral medications, treatment algorithms have failed to take into account quality of life improvements resulting from more rapid and complete treatment response.
CONCLUSIONS
Topical mesalazine therapy is superior to oral therapy in distal ulcerative colitis for both therapeutic response and drug delivery. Practice patterns should be re-evaluated in light of this information.
Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Combined Modality Therapy; Drug Delivery Systems; Drug Prescriptions; Humans; Mesalamine; Treatment Outcome
PubMed: 21385194
DOI: 10.1111/j.1365-2036.2011.04619.x -
Inflammatory Bowel Diseases May 2007Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylic acid (5-ASA). Studies with 5-ASA treatment in... (Review)
Review
Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylic acid (5-ASA). Studies with 5-ASA treatment in which serum creatinine or creatinine clearance was measured regularly show that nephrotoxicity is exceptional (mean rate of only 0.26% per patient-year). There have been several case reports, including 46 patients, of renal disease associated with 5-ASA treatment in patients with IBD. 5-ASA treatment-related nephrotoxicity is reported most often within the first 12 months, but also delayed presentation after several years has been shown. The absence of a clear relationship between 5-ASA dose and the risk of nephrotoxicity suggests that this complication is idiosyncratic rather than dose-related. Most of the patients with renal disease associated with 5-ASA treatment suffered interstitial nephritis, with symptoms and signs being nonspecific, which may delay detection for many months. The nephrotoxicity potential of mesalazine and sulfasalazine seems to be similar. The risk with different oral preparations of 5-ASA is probably too small to influence the choice of agent. Mesalazine should be withdrawn when renal impairment manifests in a patient with IBD; if this does not result in a fall in serum creatinine, then renal biopsy should be considered. A trial of high-dose steroid may be recommended in patients whose renal function does not respond to drug withdrawal. The optimal monitoring schedule of serum creatinine in patients receiving 5-ASA treatment remains to be established, as there is no evidence to date that either the test, or the frequency of testing, improves patient outcomes.
Topics: Animals; Dose-Response Relationship, Drug; Humans; Inflammatory Bowel Diseases; Kidney; Kidney Diseases; Mesalamine; Nephritis, Interstitial
PubMed: 17243140
DOI: 10.1002/ibd.20099 -
Alimentary Pharmacology & Therapeutics Nov 2007Oral mesalazine (mesalamine, 5-aminosalicylic acid) formulations are effective in the treatment of active ulcerative colitis. All formulations contain the same active... (Review)
Review
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.
Topics: Acute Disease; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Delayed-Action Preparations; Humans; Mesalamine; Remission Induction; Treatment Outcome
PubMed: 17944732
DOI: 10.1111/j.1365-2036.2007.03471.x -
Expert Opinion on Drug Metabolism &... Oct 20095-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been approved for the... (Review)
Review
BACKGROUND
5-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been approved for the treatment of UC.
OBJECTIVE
To summarize current data on balsalazide and to discuss its impact on management of UC.
METHODS
A systematic review of published literature was performed on PubMed using the search terms 'Balsalazide' and 'Colazal(TM)'. The Cochrane database was also reviewed.
RESULTS
Balsalzide, a 5-ASA prodrug, ulilizes azoreduction by colonic bacteria to achieve a sustained release of active 5-ASA throughout the colon. A recent clinical trial has demonstrated balsalazide 6.7 g/day to be superior to placebo in inducing remission in symptomatic UC. The drug is well tolerated with a safety profile comparable to other oral 5-ASA agents. The current data suggests that symptomatic remission occurs with both greater swiftness and greater frequency when compared with mesalamine.
CONCLUSION
Balsalazide is approved for the treatment of mild-to-moderate active UC. It is efficacious for the induction of remission in mild to moderate UC and has a favorable safety profile, with the added advantages of greater efficacy of remission induction and rapidity of onset.
Topics: Clinical Trials as Topic; Colitis, Ulcerative; Delayed-Action Preparations; Gastrointestinal Agents; Humans; Mesalamine; Phenylhydrazines; Prodrugs; Remission Induction
PubMed: 19743890
DOI: 10.1517/17425250903206996 -
Alimentary Pharmacology & Therapeutics Oct 2006Sulfasalazine was the first aminosalicylate to be used for induction and maintenance therapy of ulcerative colitis (UC). Initial trials demonstrated a dose response that... (Review)
Review
Sulfasalazine was the first aminosalicylate to be used for induction and maintenance therapy of ulcerative colitis (UC). Initial trials demonstrated a dose response that was compromised by dose-related intolerance. Recognition that the 5-aminosalicylic acid moiety (5-ASA, mesalazine) is the active ingredient of sulfasalazine has allowed the development of sulpha-free formulations of mesalazine and alternative azo-bond derivatives (olsalazine, balsalazide) that substantially reduce the dose-related (and allergic) consequences of the sulfapyridine moiety of sulfasalazine. Dose-ranging studies of mesalazine formulations for induction of remission have demonstrated increased efficacy of oral mesalazine up to 4-4.8 g/day, particularly in patients with more moderate disease activity. Combination therapy with oral and rectal mesalazine provide additional efficacy for patients with both distal and extensive colitis. The mesalazine formulations have dose-related benefits without dose-related side effects. In contrast, the azo-bond formulations are compromised by secretory diarrhoea at doses providing greater than 2-2.4 g/day of mesalazine. There are less data regarding dose-related benefits of aminosalicylates to maintain remissions in UC greater than 1.6 g/day of mesalazine, although the absence of dose-related side effects allows continuation of the same inductive dose through maintenance treatment without dose-related toxicity.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Drug Administration Schedule; Humans; Mesalamine; Remission Induction; Sulfasalazine; Treatment Outcome
PubMed: 16961743
DOI: 10.1111/j.1365-2036.2006.03058.x -
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