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PloS One 2016We performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
We performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate (BDP) to active oral controls in patients with mild-to-moderate ulcerative colitis (UC). A subgroup-analysis compared the effectiveness of BDP and 5-ASA.
METHODS
Literature research was performed in different databases, as well as manual search to identify abstracts from international meetings with data not included in extensive publications. Experts in the field and companies involved in BDP development and manufacture were contacted to identify unpublished studies used for registration purposes. Dichotomous data were pooled to obtain odds ratio meta-analysis.
RESULTS
Five randomized controlled trials that compared oral BDP 5mg/day vs. all oral active controls in treating UC were identified as eligible. Efficacy and safety have been addressed after 4-week treatment period. One study evaluated efficacy and safety of BDP vs. prednisone and 4 of BDP vs. 5-ASA. Treatment with oral BDP 5 mg/day induces a significant better clinical response compared to oral 5-ASA (OR 1.86, 95% CI = 1.23-2.82, P = 0.003). The effect is detectable even when the comparison to prednisone is added (OR 1.41, 95% CI = 1.03-1.93, P = 0.03). Data on remission indicate that the potential clinical efficacy of BDP may be better than 5-ASA (OR 1.55, 95% CI = 1.00-2.40, P = 0.05). This difference is lost when the comparison with prednisone is added (OR 1.30, 95% CI = 0.76-2.23, P = 0.34). The safety analysis showed no differences between BDP and 5-ASA (OR 0.55, 95% CI = 0.24-1.27, P = 0.16). The lack of difference is maintained even when the study with prednisone is added (OR 0.67, 95% CI = 0.44-1.01, P = 0.06). However, the trend of difference is clear and indicates a more favourable safety profile of BDP compared to 5-ASA and PD.
CONCLUSIONS
Oral prolonged release BDP showed a superior efficacy vs. oral 5-ASA in inducing clinical improvement of mild-to-moderate UC with a similar safety profile.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Beclomethasone; Colitis, Ulcerative; Drug Administration Schedule; Humans; Mesalamine; Patient Safety; Prednisone; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27846307
DOI: 10.1371/journal.pone.0166455 -
Digestive Diseases (Basel, Switzerland) 2009Collagenous and lymphocytic colitis are well-described conditions causing chronic watery diarrhoea. A peak incidence from 60 to 70 years of age with a female... (Review)
Review
Collagenous and lymphocytic colitis are well-described conditions causing chronic watery diarrhoea. A peak incidence from 60 to 70 years of age with a female predominance mainly in collagenous colitis is observed. Both conditions are characterised by a (near) normal colonoscopy, but with specific histologic findings on colonic biopsies. Histopathologically, both conditions are characterised by distinct epithelial abnormalities and a dense lymphoplasmocytic infiltrate. Distinct features consist of a characteristic collagen band deposition in the subepithelial layer in collagenous colitis and a markedly increased number of intra-epithelial lymphocytes in lymphocytic colitis. Although most cases are idiopathic, certain drugs can induce microscopic colitis. In addition, either condition can be associated with coeliac disease. For a long time patients with microscopic colitis were treated with non-specific anti-diarrhoeal agents, anti-inflammatory agents such as mesalazine, or systemic steroids, but with disappointing results. Bismuth subsalicylate was reported to be effective in a small controlled series of patients with collagenous colitis. Now, randomised controlled trials have shown the effectiveness of budesonide over placebo in collagenous colitis and more recently in lymphocytic colitis. The histologic response is variable, but a decrease in the subepithelial collagen layer and a decrease in the lymphoplasmocytic infiltrate in the lamina propria is observed in about half of the patients. In general, patients respond within 2 weeks with no major side effects. However, relapse is common (63-80% of patients) when budesonide is stopped. Longer-term treatment is effective but does not seem to reduce relapse rates upon discontinuation.
Topics: Animals; Antidiarrheals; Colitis, Collagenous; Colitis, Lymphocytic; Diarrhea; Humans
PubMed: 20203510
DOI: 10.1159/000268134 -
British Journal of Clinical Pharmacology Oct 2019The comparative efficacy, safety and tolerability of budesonide-MMX and oral mesalamine in active, mild-to-moderate ulcerative colitis (UC) are unclear. We conducted a... (Comparative Study)
Comparative Study Meta-Analysis
AIMS
The comparative efficacy, safety and tolerability of budesonide-MMX and oral mesalamine in active, mild-to-moderate ulcerative colitis (UC) are unclear. We conducted a network meta-analysis to fill this evidence gap.
METHODS
We searched PubMed, Scopus, Embase, the Cochrane Library, clinical trial registries, regulatory agencies' websites and international conference proceedings, up to July 2018, to identify randomized controlled trials of adult patients with active, mild-to-moderate UC, comparing budesonide-MMX or mesalamine against placebo, or against each other, or different dosing strategies, for induction of remission. Two reviewers independently abstracted study data and outcomes, and assessed each trial's risk-of-bias.
RESULTS
We identified and synthesized evidence from 15 eligible trials including 4083 participants. Budesonide-MMX 9 mg/day and mesalamine >2.4 g/day had similar efficacy for induction of clinical and endoscopic remission (OR = 0.97; 0.59-1.60), both showing superiority over placebo (OR = 2.68; 1.75-4.10, and OR = 2.75; 1.94-3.90, respectively). Furthermore, mesalamine >2.4 g/day was more efficacious than mesalamine 1.6-2.4 g/day (odds ratio = 1.27; 1.03-1.56). Secondary analyses showed that mesalamine >2.4 g/day ranks at the top among comparator treatments regarding safety (serious adverse events; surface under the cumulative ranking area [SUCRA] 79.2%) and tolerability (treatment discontinuations or withdrawals from the study due to adverse events; SUCRA 96.7%). There was no evidence of inconsistency, while heterogeneity between studies and risk of publication bias were low.
CONCLUSION
Budesonide-MMX and mesalamine >2.4 g/day had similar efficacy for induction of clinical and endoscopic remission in active, mild-to-moderate UC; however, mesalamine >2.4 g/day showed better tolerability. Further high-quality research is warranted.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colitis, Ulcerative; Delayed-Action Preparations; Glucocorticoids; Humans; Mesalamine; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 31269287
DOI: 10.1111/bcp.14051 -
Reviews in Medical Virology Mar 2023The susceptibility, risk factors, and prognosis of COVID-19 in patients with inflammatory bowel disease (IBD) remain unknown. Thus, our study aims to assess the... (Meta-Analysis)
Meta-Analysis Review
The susceptibility, risk factors, and prognosis of COVID-19 in patients with inflammatory bowel disease (IBD) remain unknown. Thus, our study aims to assess the prevalence and clinical outcomes of COVID-19 in IBD. We searched PubMed, EMBASE, and medRxiv from 2019 to 1 June 2022 for cohort and case-control studies comparing the prevalence and clinical outcomes of COVID-19 in patients with IBD and in the general population. We also compared the outcomes of patients receiving and not receiving 5-aminosalicylates (ASA), tumour necrosis factor antagonists, biologics, systemic corticosteroids, or immunomodulators for IBD. Thirty five studies were eligible for our analysis. Pooled odds ratio of COVID-19-related hospitalisation, intensive care unit (ICU) admission, or death in IBD compared to in non-IBD were 0.58 (95% confidence interval (CI) = 0.28-1.18), 1.09 (95% CI = 0.27-4.47), and 0.67 (95% CI = 0.32-1.42), respectively. Inflammatory bowel disease was not associated with increased hospitalisation, ICU admission, or death. Susceptibility to COVID-19 did not increase with any drugs for IBD. Hospitalisation, ICU admission, and death were more likely with 5-ASA and corticosteroid use. COVID-19-related hospitalisation (Odds Ratio (OR): 0.53; 95% CI = 0.38-0.74) and death (OR: 0.13; 95% CI = 0.13-0.70) were less likely with Crohn's disease than ulcerative colitis (UC). In conclusion, IBD does not increase the mortality and morbidity of COVID-19. However, physicians should be aware that additional monitoring is needed in UC patients or in patients taking 5-ASA or systemic corticosteroids.
Topics: Humans; COVID-19; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Adrenal Cortex Hormones; Mesalamine
PubMed: 36504172
DOI: 10.1002/rmv.2414 -
Inflammatory Bowel Diseases Nov 2015In some studies, 5-aminosalicylates as a class have been associated with protective effects against colorectal cancer in inflammatory bowel disease. In practice, only... (Meta-Analysis)
Meta-Analysis Review
Mesalamine, but Not Sulfasalazine, Reduces the Risk of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: An Agent-specific Systematic Review and Meta-analysis.
BACKGROUND
In some studies, 5-aminosalicylates as a class have been associated with protective effects against colorectal cancer in inflammatory bowel disease. In practice, only mesalamine at doses greater than 1.2 g per day is currently widely in this setting. The specific impact of mesalamine at these doses has not has not previously been determined.
METHODS
We performed a systematic review and meta-analysis of the effect of mesalamine on risk of colorectal neoplasia (CRN) from prior cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. A quality assessment was made of all included studies.
RESULTS
Mesalamine was associated with a modest reduction in the odds ratio (OR) of CRN (OR = 0.6, 95% confidence interval, 0.4-0.9, P = 0.04). This effect was only noted in hospital-based studies and only in the reduction of all CRN (not cancers alone). Patients prescribed doses >1.2 g per day had a lower risk of CRN (OR = 0.5, 95% confidence interval, 0.3-0.9, P = 0.02) than lower doses. This effect was also only present in the hospital-based studies. In contrast, there was no reduction in the risk of CRN in patients prescribed sulfasalazine (OR = 0.8, 95% confidence interval, 0.5-1.2, P = 0.3), regardless of study setting.
CONCLUSIONS
Mesalamine, particularly at doses >1.2 g per day, produces a modest reduction in the risk of CRN in inflammatory bowel disease patient populations from referral centers. Sulfasalazine does not seem to reduce the risk. No benefit was noted in population-based studies.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colorectal Neoplasms; Humans; Inflammatory Bowel Diseases; Mesalamine; Risk Assessment; Sulfasalazine
PubMed: 26296062
DOI: 10.1097/MIB.0000000000000540 -
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 -
Alimentary Pharmacology & Therapeutics Oct 2023Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat.
AIM
To assess the efficacy of medical treatments for UP.
METHODS
We searched MEDLINE, EMBASE, and CENTRAL on 23 November 2022 for randomised controlled trials (RCTs) of medical therapy for adults with UP. Primary outcomes included induction and maintenance of clinical remission. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome.
RESULTS
We included 53 RCTs (n = 4096) including 46 induction studies (n = 3731) and seven maintenance studies (n = 365). First-line therapies included topical 5-aminosalicylic acid (5-ASA), conventional corticosteroids, budesonide, and oral 5-ASA. Therapy for refractory UP included topical tacrolimus and small molecules. Topical 5-ASA was superior to placebo for induction (RR 2.72, 95% CI 1.94-3.82) and maintenance of remission (RR 2.09, 95% CI 1.26-3.46). Topical corticosteroids were superior to placebo for induction of remission (RR 2.83, 95% CI 1.62-4.92). Topical budesonide was superior to placebo for induction of remission (RR 2.34, 95% CI 1.44-3.81). Combination therapy with topical 5-ASA and topical corticosteroids was superior to topical monotherapy with either agent. Topical tacrolimus was superior to placebo. Etrasimod was superior to placebo for induction (RR 4.71, 95% CI 1.2-18.49) and maintenance of remission (RR 2.08, 95% CI 1.31-3.32).
CONCLUSIONS
Topical 5-ASA and corticosteroids are effective for active UP. Topical 5-ASA may be effective for maintenance of remission. Tacrolimus may be effective for induction of remission. Etrasimod may be effective for induction and for maintenance of remission. Trials should include UP to expand the evidence base for this under-represented population.
Topics: Adult; Humans; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colitis, Ulcerative; Mesalamine; Proctitis; Remission Induction; Tacrolimus
PubMed: 37589498
DOI: 10.1111/apt.17666 -
Frontiers in Pharmacology 2024Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary...
Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary treatment, and Chinese herbal medicine shows the potential for such treatment. As a traditional Chinese herbal medicine, Danshen-related preparations have been reported to be beneficial for UC by improving coagulation function and inhibiting inflammatory responses. In spite of this, the credibility and safety of this practice are incomplete. Therefore, in order to investigate whether Danshen preparation (DSP) is effective and safe in the treatment of UC, we conducted a systematic review and meta-analysis. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database and CQVIP Database were searched for this review.The main observation indexes were the effect of DSP combined with mesalazine or DSP on the effective rate, platelet count (PLT), mean platelet volume (MPV) and C-reactive protein (CRP) of UC. The Cochrane risk of bias tool was used to assess the risk of bias. The selected studies were evaluated for quality and data processing using RevMan5.4 and Stata17.0 software. A total of 37 studies were included. Among them, 26 clinical trials with 2426 patients were included and 11 animal experimental studies involving 208 animals were included. Meta-analysis results showed that compared with mesalazine alone, combined use of DSP can clearly improve the clinical effective rate (RR 0.86%, 95% CI:0.83-0.88, < 0.00001) of UC. Furthermore it improved blood coagulation function by decreasing serum PLT and increasing MPV levels, and controlled inflammatory responses by reducing serum CRP, TNF-α, IL-6, and IL-8 levels in patients. Combining DSP with mesalazine for UC can enhance clinical efficacy. However, caution should be exercised in interpreting the results of this review due to its flaws, such as allocation concealment and uncertainty resulting from the blinding of the study. : http://www.crd.york.ac.uk/PROSPERO/myprospero.php, identifier PROSPERO: CRD42022293287.
PubMed: 38881869
DOI: 10.3389/fphar.2024.1334474 -
JAMA Jan 2014Diverticulitis is a common disease. Recent changes in understanding its natural history have substantially modified treatment paradigms. (Review)
Review
IMPORTANCE
Diverticulitis is a common disease. Recent changes in understanding its natural history have substantially modified treatment paradigms.
OBJECTIVE
To review the etiology and natural history of diverticulitis and recent changes in treatment guidelines.
EVIDENCE REVIEW
We searched the MEDLINE and Cochrane databases for English-language articles pertaining to diagnosis and management of diverticulitis published between January 1, 2000, and March 31, 2013. Search terms applied to 4 thematic topics: pathophysiology, natural history, medical management, and indications for surgery. We excluded small case series and articles based on data accrued prior to 2000. We hand searched the bibliographies of included studies, yielding a total of 186 articles for full review. We graded the level of evidence and classified recommendations by size of treatment effect, according to the guidelines from the American Heart Association Task Force on Practice Guidelines.
FINDINGS
Eighty articles met criteria for analysis. The pathophysiology of diverticulitis is associated with altered gut motility, increased luminal pressure, and a disordered colonic microenvironment. Several studies examined histologic commonalities with inflammatory bowel disease and irritable bowel syndrome but were focused on associative rather than causal pathways. The natural history of uncomplicated diverticulitis is often benign. For example, in a cohort study of 2366 of 3165 patients hospitalized for acute diverticulitis and followed up for 8.9 years, only 13.3% of patients had a recurrence and 3.9%, a second recurrence. In contrast to what was previously thought, the risk of septic peritonitis is reduced and not increased with each recurrence. Patient-reported outcomes studies show 20% to 35% of patients managed nonoperatively progress to chronic abdominal pain compared with 5% to 25% of patients treated operatively. Randomized trials and cohort studies have shown that antibiotics and fiber were not as beneficial as previously thought and that mesalamine might be useful. Surgical therapy for chronic disease is not always warranted.
CONCLUSIONS AND RELEVANCE
Recent studies demonstrate a lesser role for aggressive antibiotic or surgical intervention for chronic or recurrent diverticulitis than was previously thought necessary.
Topics: Anti-Bacterial Agents; Dietary Fiber; Diverticulitis; Humans; Practice Guidelines as Topic; Risk; Sigmoid Diseases
PubMed: 24430321
DOI: 10.1001/jama.2013.282025 -
The American Journal of Gastroenterology Apr 2011Acute severe ulcerative colitis (ASC) is a potentially life-threatening disease. We aimed to formulate guidelines for managing ASC in children based on systematic review... (Review)
Review
Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN.
OBJECTIVES
Acute severe ulcerative colitis (ASC) is a potentially life-threatening disease. We aimed to formulate guidelines for managing ASC in children based on systematic review of the literature and robust consensus process. This manuscript is a product of a joint effort of the ECCO (European Crohn's and Colitis Organization), the Pediatric Porto Inflammatory Bowel Disease (IBD) Working group of ESPGHAN (European Society of Pediatric Gastroenterology, Hepatology, and Nutrition) and ESPGHAN.
METHODS
A group of 19 experts in pediatric IBD participated in an iterative consensus process including two face-to-face meetings. A total of 17 predefined questions were addressed by working subgroups based on a systematic review of the literature.
RESULTS
The recommendations and practice points were eventually endorsed with a consensus rate of at least 95% regarding: definitions, initial evaluation, standard therapy, timing of second-line therapy, the role of endoscopic evaluation and heparin prophylaxis, how to administer second-line medical therapy, how to assess response, surgical considerations, and discharge recommendations. A management flowchart is presented based on daily scoring of the Pediatric Ulcerative Colitis Activity Index (PUCAI), along with 28 formal recommendations and 34 practice points.
CONCLUSIONS
These guidelines provide clinically useful points to guide the management of ASC in children. Taken together, the recommendations offer a standardized protocol that allows effective monitoring of disease progress and timely treatment escalation when needed.
Topics: Acute Disease; Adrenal Cortex Hormones; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Colitis, Ulcerative; Endoscopy, Digestive System; Heparin; Humans; Mesalamine; Nutritional Support; Palliative Care; Severity of Illness Index; Thromboembolism
PubMed: 21224839
DOI: 10.1038/ajg.2010.481