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Journal of Pediatric Gastroenterology... Dec 2014The aim of the study was to assess the safety and efficacy of high- and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The aim of the study was to assess the safety and efficacy of high- and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of children with mild-to-moderately active ulcerative colitis.
METHODS
Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of ≥ 10 to ≤ 55 and a truncated Mayo Score of ≥ 1 for both rectal bleeding and stool frequency, were enrolled. They received body weight-dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27-71 mg · g(-1) · day(-1)) or high-dose group (53-118 mg · g(-1) · day(-1)). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score ≥ 10 with a decrease from baseline by ≥ 20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity.
RESULTS
The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low- and high-dose groups, respectively (P = 0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups.
CONCLUSIONS
Both low- and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose.
Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Colitis, Ulcerative; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Mesalamine
PubMed: 25419597
DOI: 10.1097/MPG.0000000000000530 -
Internal Medicine (Tokyo, Japan) Mar 2023In drug-induced lupus (DIL), symptoms similar to those of systemic lupus erythematosus (SLE) usually resolve after discontinuation of the offending drug. A...
In drug-induced lupus (DIL), symptoms similar to those of systemic lupus erythematosus (SLE) usually resolve after discontinuation of the offending drug. A 41-year-old-woman with a history of ulcerative colitis presented with polyarthritis and myositis and was positive for anti-double stranded (ds) DNA IgG antibody. After discontinuation of mesalazine, the symptoms resolved, and the antibody titer decreased. The patient was diagnosed with DIL. Six months later, lupus myocarditis developed. After treatment with glucocorticoids, cyclophosphamide, intravenous immunoglobulin, and an intra-aortic balloon pump, she showed dramatic improvement. Patients with DIL and an immunological predisposition, such as anti-dsDNA antibodies, may have SLE and should be carefully monitored.
Topics: Female; Humans; Adult; Mesalamine; Myocarditis; Lupus Erythematosus, Systemic; Immunoglobulins, Intravenous; Cyclophosphamide; Antibodies, Antinuclear
PubMed: 35945022
DOI: 10.2169/internalmedicine.9613-22 -
United European Gastroenterology Journal Nov 2019
Topics: Humans; Budesonide; Colitis, Ulcerative; Anti-Inflammatory Agents, Non-Steroidal; Mesalamine
PubMed: 31700627
DOI: 10.1177/2050640619878588 -
Alimentary Pharmacology & Therapeutics Sep 1999
Topics: Anti-Inflammatory Agents, Non-Steroidal; Delayed-Action Preparations; Humans; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Mesalamine
PubMed: 10469474
DOI: 10.1046/j.1365-2036.1999.0612e.x -
Journal of the American Heart... Dec 2022Background The gut and gut microbiota, which were previously neglected in blood pressure regulation, are becoming increasingly recognized as factors contributing to...
Background The gut and gut microbiota, which were previously neglected in blood pressure regulation, are becoming increasingly recognized as factors contributing to hypertension. Diseases affecting the gut such as inflammatory bowel disease (IBD) present with aberrant energy metabolism of colonic epithelium and gut dysbiosis, both of which are also mechanisms contributing to hypertension. We reasoned that current measures to remedy deficits in colonic energy metabolism and dysbiosis in IBD could also ameliorate hypertension. Among them, 5-aminosalicylic acid (5-ASA; mesalamine) is a PPARγ (peroxisome proliferator-activated receptor gamma) agonist. It attenuates IBD by a dual mechanism of selectively enhancing colonic epithelial cell energy metabolism and ameliorating gut dysbiosis. Methods and Results A total of 2 groups of 11- to 12-week-old male, hypertensive, Dahl salt-sensitive (S) rats were gavaged with (n=10) or without (n=10) 5-aminosalicylic acid (150 mg/kg) for 4 weeks. Rats receiving 5-aminosalicylic acid treatment had a lower mean blood pressure than controls (145±3 mm Hg versus 153±4 mm Hg; <0.0001). This reduction in blood pressure was accompanied by increased activity of PPARγ, increased expression of energy metabolism-related genes, and lowering of the Firmicutes/Bacteroidetes ratio in the colon, the reduction of which is a marker for the correction of gut dysbiosis. Furthermore, these data were consistent with the American Gut Project wherein the Firmicutes/Bacteroidetes ratio of non-IBD (n=611) patients was significantly lower than patients with IBD (n=631). Conclusions 5-Aminosalicylic acid could be repurposed for hypertension by specifically enhancing the gut energy metabolism and correction of microbiota dysbiosis.
Topics: Rats; Male; Animals; Mesalamine; PPAR gamma; Dysbiosis; Drug Repositioning; Rats, Inbred Dahl; Inflammatory Bowel Diseases; Hypertension; Drug Delivery Systems
PubMed: 36533597
DOI: 10.1161/JAHA.122.027893 -
Journal of Medical Case Reports Feb 2018Myocarditis is a rare complication of therapy with mesalazine, a drug widely prescribed in the treatment of inflammatory bowel disease.
BACKGROUND
Myocarditis is a rare complication of therapy with mesalazine, a drug widely prescribed in the treatment of inflammatory bowel disease.
CASE PRESENTATION
We report a case of myocarditis occurring in a 49-year-old British man 10 days following initiation of mesalazine therapy for treatment of ulcerative colitis. He presented with troponin-positive chest pain, and the diagnosis of myocarditis was confirmed on the basis of cardiac magnetic resonance imaging, which showed subepicardial delayed gadolinium enhancement in the basal to middle inferior and inferolateral segments of the heart. The patient's symptoms and condition improved upon stopping mesalazine, and he made a full recovery.
CONCLUSIONS
Mesalazine-induced myocarditis may be more common than first appreciated and is potentially fatal. Therefore, it is imperative that clinicians be aware of this potentially life-threatening adverse effect of mesalazine therapy and warn patients to seek urgent medical attention if cardiac symptoms arise.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Magnetic Resonance Imaging; Male; Mesalamine; Middle Aged; Myocarditis
PubMed: 29467009
DOI: 10.1186/s13256-017-1557-z -
Alimentary Pharmacology & Therapeutics Sep 2015The incidence of diverticulosis and diverticular disease of the colon, including diverticulitis, is increasing worldwide, and becoming a significant burden on national... (Review)
Review
BACKGROUND
The incidence of diverticulosis and diverticular disease of the colon, including diverticulitis, is increasing worldwide, and becoming a significant burden on national health systems. Treatment of patients with diverticulosis and DD is generally based on high-fibre diet and antibiotics, respectively. However, new pathophysiological knowledge suggests that further treatment may be useful.
AIM
To review the current treatment of diverticulosis and diverticular disease.
METHODS
A search of PubMed and Medline databases was performed to identify articles relevant to the management of diverticulosis and diverticular disease. Major international conferences were also reviewed.
RESULTS
Two randomised controlled trials (RCT) found the role of antibiotics in managing acute diverticulitis to be questionable, particularly in patients with no complicating comorbidities. One RCT found mesalazine to be effective in preventing acute diverticulitis in patients with symptomatic uncomplicated diverticular disease. The role of rifaximin or mesalazine in preventing diverticulitis recurrence, based on the results of 1 and 4 RCTs, respectively, remains unclear. RCTs found rifaximin and mesalazine to be effective in treating symptomatic uncomplicated diverticular disease. The use of probiotics in diverticular disease and in preventing acute diverticulitis occurrence/recurrence appears promising but unconclusive. Finally, the role of fibre in treating diverticulosis remains unclear.
CONCLUSIONS
Available evidence suggests that antibiotics have a role only in the treatment of complicated diverticulitis. It appears to be some evidence for a role for rifaximin and mesalazine in treating symptomatic uncomplicated diverticular disease. Finally, there is not currently adequate evidence to recommend any medical treatment for the prevention of diverticulitis recurrence.
Topics: Anti-Bacterial Agents; Dietary Fiber; Diverticulitis, Colonic; Diverticulum; Humans; Mesalamine; Probiotics; Randomized Controlled Trials as Topic; Recurrence; Rifamycins; Rifaximin
PubMed: 26202723
DOI: 10.1111/apt.13322 -
European Review For Medical and... Aug 2020Diverticulitis is the most severe form of Diverticular disease (DD). An effective treatment strategy for its prevention has not yet been defined. This review aimed to... (Review)
Review
Diverticulitis is the most severe form of Diverticular disease (DD). An effective treatment strategy for its prevention has not yet been defined. This review aimed to provide a viewpoint on the role of mesalazine, also note as 5-aminosalicylic acid (5-ASA), in the prevention of diverticulitis. A systematic electronic search of relevant articles was performed using PubMed, Embase, Scopus, and Cochrane. Randomized controlled trials (RCTs), open trials, and retrospective studies, published between January 1999 and January 2020, were identified. Twelve eligible studies that analyzed primary or secondary outcomes of diverticulitis were included. The population included patients with symptomatic uncomplicated diverticular disease (SUDD), or patients with a history of diverticulitis. All studies compared 5-ASA to placebo, rifaximin, or other treatments. Two studies, including 359 patients, assessed the efficacy of 5-ASA in preventing the first appearance of diverticulitis in patients with SUDD. Of these, one showed that 5-ASA was effective, and one did not. Ten studies, including 2.995 patients, assessed the efficacy of 5-ASA treatment in preventing the recurrence of diverticulitis in patients with a history of diverticulitis. Four studies showed that 5-ASA had a certain degree of efficacy. All four RCTs demonstrated that 5-ASA did not significantly reduce the rate of diverticulitis recurrence. In a retrospective trial, 5-ASA was less effective than rifaximin in preventing diverticulitis recurrence. In an open trial, there was no difference between 5-ASA and probiotic treatment. Overall, there is currently conflicting evidence regarding the efficacy of 5-ASA treatment in the prevention of diverticulitis and further RCTs are needed.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diverticulitis; Humans; Mesalamine; Probiotics; Rifaximin
PubMed: 32767345
DOI: 10.26355/eurrev_202008_22504 -
World Journal of Gastroenterology Oct 2006Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in... (Review)
Review
Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in combination therapy to improve efficacy and concomitant drug pharmacokinetics, or in chemoprevention against inflammatory bowel disease (IBD)-related colonic carcinoma has not yet been completely elucidated. Therapeutic success of mesalazine may be optimized by a combination of high dose and low frequency of dosage to improve compliance. Therefore, due to its superior safety profile and pharmacokinetic characteristics, mesalazine is preferable to sulphasalazine. This paper reviews the literature concerning mechanisms of action, indications and off-label use, pharmacokinetic properties and formulations, therapeutic efficacy, compliance, paediatric indications, chemoprevention, and safety issues and adverse event profile of mesalazine treatment versus sulphasalazine. It also highlights these controversies in order to clarify the potential benefits of mesalazines in IBD therapy and evidence for its use.
Topics: Adenocarcinoma; Anti-Inflammatory Agents, Non-Steroidal; Colonic Neoplasms; Humans; Inflammatory Bowel Diseases; Mesalamine; Sulfasalazine; Treatment Failure; Treatment Refusal
PubMed: 17036381
DOI: 10.3748/wjg.v12.i38.6115 -
Clinical Gastroenterology and... Jan 2019Although proctitis is the most limited form of ulcerative colitis, it causes unpleasant symptoms. Topical mesalamine, the standard treatment, is not always effective. We... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Although proctitis is the most limited form of ulcerative colitis, it causes unpleasant symptoms. Topical mesalamine, the standard treatment, is not always effective. We conducted a randomized phase 2 trial to determine the efficacy and safety of 2 doses of a budesonide suppository vs mesalamine suppositories vs combined budesonide and mesalamine suppositories for proctitis.
METHODS
We performed a prospective, double-blind, double-dummy, multicenter trial in 337 patients with active proctitis to compare the efficacies of 4 different suppository treatments. Patients were randomly assigned to groups given 2 mg budesonide suppositories (2 mg BUS; n = 89 patients), 4 mg BUS (n = 79), 1 g mesalamine suppositories (1 g MES; n = 81), or the combination of 2 mg BUS and 1 g MES (n = 88). The study was performed from November 2013 through July 2015 at 36 study sites in Europe and Russia. The primary end point was the time to resolution of clinical symptoms, defined as the first of 3 consecutive days with a score of 0 for rectal bleeding and stool frequency.
RESULTS
The mean time to resolution of symptoms in the 4 mg BUS (29.8 days) and combination of 2 mg BUS and 1 g MES (29.3 days) groups resembled that of the standard 1 g MES treatment (29.2 days), but was significantly longer in the 2 mg BUS group (35.5 days). Furthermore, proportions of patients with deep, clinical, and endoscopic remission, as well as mucosal healing, were similar among the 1 g MES, 4 mg BUS, and combination therapy groups, but significantly lower in the group that received 2 mg BUS. No safety signals were observed, and the patients' treatment acceptance was high (67%-85% of patients).
CONCLUSIONS
In a multicenter randomized trial, we found that the efficacy and safety of 4 mg BUS in treatment of active proctitis did not differ significantly from those of 1 g MES. Budesonide suppositories offer an alternative therapy to mesalamine for topical treatment of proctitis. Clinicaltrialsregister.eu no: 2012-003362-41.
Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Double-Blind Method; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Europe; Female; Humans; Male; Mesalamine; Middle Aged; Proctitis; Prospective Studies; Russia; Suppositories; Treatment Outcome; Young Adult
PubMed: 29702300
DOI: 10.1016/j.cgh.2018.04.027