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Digestion 2023Two major types of 5-aminosalicylic acid (5-ASA)-containing preparations, namely, mesalazine/5-ASA and sulfasalazine (SASP), are currently used as first-line therapy for... (Review)
Review
BACKGROUND
Two major types of 5-aminosalicylic acid (5-ASA)-containing preparations, namely, mesalazine/5-ASA and sulfasalazine (SASP), are currently used as first-line therapy for ulcerative colitis. Recent reports show that optimization of 5-ASA therapy is beneficial for both patient outcomes and healthcare costs. Although 5-ASA and SASP have good efficacy and safety profiles, clinicians occasionally encounter patients who develop 5-ASA intolerance.
SUMMARY
The most common symptoms of acute 5-ASA intolerance syndrome are exacerbation of diarrhea, fever, and abdominal pain. Patients who discontinue 5-ASA therapy because of intolerance have a higher risk of adverse clinical outcomes, such as hospital admission, colectomy, need for advanced therapies, and loss of response to anti-tumor necrosis factor (TNF) biologics. When patients develop symptoms of 5-ASA intolerance, the clinician should consider changing the type of 5-ASA preparation. Recent genome-wide association studies and meta-analyses have shown that 5-ASA allergy is associated with certain single-nucleotide polymorphisms. Although there are no modalities or biomarkers for diagnosing 5-ASA intolerance, the drug-induced lymphocyte stimulation test can be used to assist in the diagnosis of acute 5-ASA intolerance syndrome with high specificity and low sensitivity. This review presents a general overview of 5-ASA and SASP in the treatment of inflammatory bowel disease and discusses the latest insights into 5-ASA intolerance.
KEY MESSAGES
5-ASA is used as first-line therapy for ulcerative colitis. Optimization of 5-ASA may be beneficial for patient outcomes and healthcare systems. Acute 5-ASA intolerance syndrome is characterized by diarrhea, fever, and abdominal pain. Periodic renal function monitoring is recommended for patients receiving 5-ASA.
Topics: Humans; Mesalamine; Colitis, Ulcerative; Anti-Inflammatory Agents, Non-Steroidal; Genome-Wide Association Study; Remission Induction; Administration, Oral; Sulfasalazine; Fever; Abdominal Pain
PubMed: 36366816
DOI: 10.1159/000527452 -
Gastroenterology Aug 2023
Topics: Humans; Colitis, Ulcerative; Interleukin-2; Mesalamine; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37030335
DOI: 10.1053/j.gastro.2023.03.230 -
Journal of Crohn's & Colitis Jul 20215-Aminosalicylates [5-ASAs] are the mainstay of treatment for ulcerative colitis [UC]. The optimum preparation, dose, and route of administration for UC remain unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
5-Aminosalicylates [5-ASAs] are the mainstay of treatment for ulcerative colitis [UC]. The optimum preparation, dose, and route of administration for UC remain unclear. We conducted a network meta-analysis to examine this issue.
METHODS
We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to December 2020. We included randomised controlled trials [RCTs] comparing oral, topical, or combined oral and topical 5-ASAs, with each other or placebo for induction of remission or prevention of relapse of UC. Results were reported as pooled relative risks [RRs] with 95% confidence intervals [CIs] to summarise effect of each comparison tested, with treatments ranked according to P-score.
RESULTS
We identified 40 RCTs for induction of remission and 23 for prevention of relapse. Topical mesalazine [P-score 0.99], or oral and topical mesalazine combined [P-score 0.87] ranked first and second for clinical and endoscopic remission combined. Combined therapy ranked first in trials where ≥50% of patients had left-sided/extensive disease, and topical mesalazine first in trials where ≥50% of patients had proctitis/proctosigmoiditis. High-dose [≥3.3 g/day] oral mesalazine ranked third in most analyses, with the most trials and most patients. For relapse of disease activity, combined therapy and high-dose oral mesalazine ranked first and second, with topical mesalazine third. 5-ASAs were safe and well tolerated, regardless of regimen.
CONCLUSIONS
Our results support previous evidence; however, higher doses of oral mesalazine had more evidence for induction of remission than combined therapy and were significantly more efficacious than lower doses. Future RCTs should better establish the role of combined therapy for induction of remission, as well as optimal doses of oral 5-ASAs to prevent relapse.
Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Humans; Mesalamine; Network Meta-Analysis
PubMed: 33433562
DOI: 10.1093/ecco-jcc/jjab010 -
Clinical Gastroenterology and... Feb 2024Some patients with irritable bowel syndrome (IBS) demonstrate low-grade inflammation in the intestine. Mesalamine, which has anti-inflammatory effects, may be an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Some patients with irritable bowel syndrome (IBS) demonstrate low-grade inflammation in the intestine. Mesalamine, which has anti-inflammatory effects, may be an efficacious treatment for IBS, but studies are conflicting. We conducted a systematic review and meta-analysis to assess efficacy and safety of mesalamine in IBS.
METHODS
We searched the medical literature up to September 14, 2022, to identify randomized controlled trials (RCTs) of mesalamine in IBS. We judged efficacy and safety using dichotomous assessments of effect on global IBS symptoms, abdominal pain, bowel habit or stool frequency, and occurrence of any adverse event. We pooled data using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs).
RESULTS
We identified 8 eligible RCTs (820 patients). Mesalamine was more efficacious than placebo for global IBS symptoms (RR of global symptoms not improving, 0.86; 95% CI, 0.79-0.95; number needed to treat = 10; 95% CI, 6-27), but not for abdominal pain or bowel habit or stool frequency. Subgroup analyses demonstrated efficacy of mesalamine in IBS with diarrhea for global IBS symptoms (RR, 0.88; 95% CI, 0.79-0.99), but not patients with other predominant bowel habits or those with post-infection IBS. Adverse event rates were no higher with mesalamine (RR, 1.20; 95% CI, 0.89-1.63) but were reported in only 5 trials.
CONCLUSIONS
Mesalamine may be modestly efficacious for global symptoms in IBS, particularly IBS with diarrhea, but quality of evidence was low. Adequately powered high quality RCTs of mesalamine in IBS are needed.
Topics: Humans; Abdominal Pain; Diarrhea; Irritable Bowel Syndrome; Mesalamine; Treatment Outcome
PubMed: 36858143
DOI: 10.1016/j.cgh.2023.02.014 -
Nutrients Dec 2022Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD). It is a chronic autoimmune inflammation of unclear etiology affecting the colon and rectum,... (Review)
Review
Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD). It is a chronic autoimmune inflammation of unclear etiology affecting the colon and rectum, characterized by unpredictable exacerbation and remission phases. Conventional treatment options for UC include mesalamine, glucocorticoids, immunosuppressants, and biologics. The management of UC is challenging, and other therapeutic options are constantly being sought. In recent years more attention is being paid to curcumin, a main active polyphenol found in the turmeric root, which has numerous beneficial effects in the human body, including anti-inflammatory, anticarcinogenic, and antioxidative properties targeting several cellular pathways and making an impact on intestinal microbiota. This review will summarize the current knowledge on the role of curcumin in the UC therapy.
Topics: Humans; Colitis, Ulcerative; Curcumin; Anti-Inflammatory Agents, Non-Steroidal; Mesalamine; Inflammation
PubMed: 36558408
DOI: 10.3390/nu14245249 -
Expert Opinion on Pharmacotherapy Aug 2016Budesonide is a synthetic corticosteroid characterized by enhanced topical potency and limited systemic bioavailability. Its use in ulcerative colitis (UC) was limited... (Review)
Review
Budesonide is a synthetic corticosteroid characterized by enhanced topical potency and limited systemic bioavailability. Its use in ulcerative colitis (UC) was limited to rectal preparations until recently when the new oral budesonide formulation incorporating the multi-matrix system technology was introduced. The purpose of this review is to evaluate the current role of oral and rectal budesonide in managing UC patients Areas covered: In this paper, we described the chemical structure and pharmacologic characteristics of the different oral and rectal budesonide preparations, provided a summary of the published trials that evaluated the efficacy and safety of budesonide in UC, and discussed the current status of its use in this population Expert opinion: Budesonide is effective in inducing remission in a subset of patients with mild-moderate UC. Nevertheless, the current evidence suggests inferiority of oral budesonide to 5-aminosalisylates (5-ASA) and systemic steroids, whereas rectal applications are comparable to other rectal steroid preparations, but still inferior to rectal 5-ASA. In clinical practice, several issues need clarification including, its exact position in the line of induction agents; the role of combining budesonide and 5-ASAs; the role of combining oral and rectal budesonide; and the role of budesonide in maintenance therapy.
Topics: Administration, Oral; Administration, Rectal; Animals; Anti-Inflammatory Agents; Biological Availability; Budesonide; Chemistry, Pharmaceutical; Colitis, Ulcerative; Humans; Mesalamine; Remission Induction; Steroids; Treatment Outcome
PubMed: 27157244
DOI: 10.1080/14656566.2016.1183648 -
Archivos Espanoles de Urologia Jul 2020Mesalazine (5-aminosalicylic acid, 5-ASA),is an anti-inflammatory drug well-established as first-line treatment in the management of inflammatory bowel disease....
Mesalazine (5-aminosalicylic acid, 5-ASA),is an anti-inflammatory drug well-established as first-line treatment in the management of inflammatory bowel disease. Nephritic colic has been described as an uncommonside effect, but very few mesalazine nephrolithiasis have been published in the literature, probably due to its underdiagnosis for not using appropriate methodology for calculi analysis. We present two cases of lithiasis in patients treated with mesalazine at high dosage, an adverse effect to betaken into account as a drug lithiasis and which is not even mentioned in the patient information leaflet.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Calculi; Humans; Kidney; Kidney Calculi; Lithiasis; Mesalamine; Nephrolithiasis
PubMed: 32633252
DOI: No ID Found -
Expert Review of Clinical Pharmacology Mar 2012Ulcerative colitis (UC) is a chronic disease of the GI tract that is characterized by mucosal inflammation in the colon. Mesalamine (mesalazine) is a 5-aminosalicylic... (Review)
Review
Ulcerative colitis (UC) is a chronic disease of the GI tract that is characterized by mucosal inflammation in the colon. Mesalamine (mesalazine) is a 5-aminosalicylic acid compound that is the first-line treatment for patients with mild-to-moderate UC. There are multiple formulations of mesalamine available, primarily differentiated by their means of delivering active mesalamine to the colon. Mesalamine has been demonstrated in randomized controlled trials to induce both clinical response and remission, and maintain clinical remission, in these patients. It has few serious adverse effects and is generally well tolerated by patients. The main areas of uncertainty with use of mesalamine in patients with UC center on the optimal dose for induction of response, how to maintain patient adherence and the role of mesalamine in cancer chemoprophylaxis. Generic forms of mesalamine have yet to be approved by regulatory bodies in the USA.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Colitis, Ulcerative; Humans; Infant; Mesalamine; Middle Aged; Patient Compliance; Randomized Controlled Trials as Topic; Remission Induction; Severity of Illness Index; Therapeutic Equivalency; Treatment Outcome; Young Adult
PubMed: 22390554
DOI: 10.1586/ecp.12.2 -
Scientific Reports Feb 2019Disruption of mucosal structure and barrier function contribute to the pathogenesis of inflammatory bowel disease (IBD). Efficacy of therapy in IBD is based on...
Disruption of mucosal structure and barrier function contribute to the pathogenesis of inflammatory bowel disease (IBD). Efficacy of therapy in IBD is based on endoscopic mucosal healing, which occurs by a dynamic interplay of epithelial cell regeneration, migration and differentiation. Both mesalamine (5-ASA) and azathioprine (AZTP) promote this process through mechanisms not clearly understood. We examined molecular pathways implicated in epithelial barrier function that were altered by 5-ASA and AZTP. Paracellular permeability induced by inflammatory mediators was mitigated by both compounds through restoration of cellular anchoring complexes. 5-ASA and AZTP induced rearrangement and membranous localization of junctional proteins and modulated genes involved in tight junctions. Intestinal organoids from wildtype-mice treated with TNF-α and IL-10- deficient-mice displayed impaired epithelial barrier with loss of membranous E-cadherin and reduced Desmoglein-2 expression. These effects were counteracted by 5-ASA and AZTP. Unlike AZTP that exhibited antiproliferative effects, 5-ASA promoted wound healing in colon epithelial cells. Both affected cellular senescence, cell cycle distribution and restricted cells in G1 or S phase without inducing apoptosis. This study provides mechanistic evidence that molecular actions of 5-ASA and AZTP on intestinal epithelia are fundamental in the resolution of barrier dysfunction.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Colitis; Epithelial Cells; Inflammation; Inflammatory Bowel Diseases; Intestines; Mesalamine; Mice; Wound Healing
PubMed: 30809073
DOI: 10.1038/s41598-019-39401-0 -
BMJ Clinical Evidence Aug 2007Diverticula (mucosal outpouching through the wall of the colon) affect over 5% of adults aged 40 years and older, but only 10-25% of affected people will develop... (Review)
Review
INTRODUCTION
Diverticula (mucosal outpouching through the wall of the colon) affect over 5% of adults aged 40 years and older, but only 10-25% of affected people will develop symptoms such as lower abdominal pain. Recurrent symptoms are common, and 5% of people with diverticula eventually develop complications such as perforation, obstruction, haemorrhage, fistulae, or abscesses.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of: treatments for uncomplicated diverticular disease; treatments to prevent complications; and treatments for acute diverticulitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 13 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antispasmodics, bran, elective surgery, increasing fibre intake, ispaghula husk, lactulose, medical treatment, mesalazine, methylcellulose, rifaximin, surgery.
Topics: Acute Disease; Diverticulitis; Diverticulitis, Colonic; Diverticulosis, Colonic; Diverticulum; Humans; Mesalamine
PubMed: 19454119
DOI: No ID Found