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The Cochrane Database of Systematic... Aug 2020Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. It was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. It was previously found that 5-ASA drugs in doses of at least 2 g/day were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis (UC). This review is an update of a previously published Cochrane Review.
OBJECTIVES
To assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators (i.e. other formulations of 5-ASA) for induction of remission in active UC. A secondary objective was to compare the efficacy and safety of once-daily dosing of oral 5-ASA versus conventional dosing regimens (two or three times daily).
SEARCH METHODS
We searched MEDLINE, Embase and the Cochrane Library on 11 June 2019. We also searched references, conference proceedings and study registers to identify additional studies.
SELECTION CRITERIA
We considered randomized controlled trials (RCTs) including adults (aged 18 years or more) with active UC for inclusion. We included studies that compared oral 5-ASA therapy with placebo, SASP, or other 5-ASA formulations. We also included studies that compared once-daily to conventional dosing as well as dose-ranging studies.
DATA COLLECTION AND ANALYSIS
Outcomes include failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events (AEs), serious adverse events (SAEs), withdrawals due to AEs, and withdrawals or exclusions after entry. We analyzed five comparisons: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once-daily dosing versus conventional dosing, 5-ASA (e.g. MMX mesalamine, Ipocol, Balsalazide, Pentasa, Olsalazine and 5-ASA micropellets) versus comparator 5-ASA (e.g. Asacol, Claversal, Salofalk), and 5-ASA dose-ranging. We calculated the risk ratio (RR) and 95% confidence interval (95% CI) for each outcome. We analyzed data on an intention-to-treat basis, and used GRADE to assess the overall certainty of the evidence.
MAIN RESULTS
We include 54 studies (9612 participants). We rated most studies at low risk of bias. Seventy-one per cent (1107/1550) of 5-ASA participants failed to enter clinical remission compared to 83% (695/837) of placebo participants (RR 0.86, 95% CI 0.82 to 0.89; 2387 participants, 11 studies; high-certainty evidence). We also observed a dose-response trend for 5-ASA. There was no difference in clinical remission rates between 5-ASA and SASP. Fifty-four per cent (150/279) of 5-ASA participants failed to enter remission compared to 58% (144/247) of SASP participants (RR 0.90, 95% CI 0.77 to 1.04; 526 participants, 8 studies; moderate-certainty evidence). There was no difference in remission rates between once-daily dosing and conventional dosing. Sixty per cent (533/881) of once-daily participants failed to enter clinical remission compared to 61% (538/880) of conventionally-dosed participants (RR 0.99, 95% CI 0.93 to 1.06; 1761 participants, 5 studies; high-certainty evidence). Eight per cent (15/179) of participants dosed once daily failed to adhere to their medication regimen compared to 6% (11/179) of conventionally-dosed participants (RR 1.36, 95% CI 0.64 to 2.86; 358 participants, 2 studies; low-certainty evidence). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Fifty per cent (507/1022) of participants in the 5-ASA group failed to enter remission compared to 52% (491/946) of participants in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.02; 1968 participants, 11 studies; moderate-certainty evidence). There was no evidence of a difference in the incidence of adverse events and serious adverse events between 5-ASA and placebo, once-daily and conventionally-dosed 5-ASA, and 5-ASA and comparator 5-ASA formulation studies. Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening UC. SASP was not as well tolerated as 5-ASA. Twenty-nine per cent (118/411) of SASP participants experienced an AE compared to 15% (72/498) of 5-ASA participants (RR 0.48, 95% CI 0.36 to 0.63; 909 participants, 12 studies; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
There is high-certainty evidence that 5-ASA is superior to placebo, and moderate-certainty evidence that 5-ASA is not more effective than SASP. Considering relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. High-certainty evidence suggests 5-ASA dosed once daily appears to be as efficacious as conventionally-dosed 5-ASA. There may be little or no difference in efficacy or safety among the various 5-ASA formulations.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Bias; Colitis, Ulcerative; Drug Administration Schedule; Humans; Induction Chemotherapy; Mesalamine; Patient Dropouts; Placebos; Randomized Controlled Trials as Topic; Remission Induction; Sulfasalazine; Treatment Failure
PubMed: 32786164
DOI: 10.1002/14651858.CD000543.pub5 -
Annals of Internal Medicine Mar 2022The value of interventions used after acute colonic diverticulitis is unclear.
BACKGROUND
The value of interventions used after acute colonic diverticulitis is unclear.
PURPOSE
To evaluate postdiverticulitis colonoscopy and interventions to prevent recurrent diverticulitis.
DATA SOURCES
MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, CINAHL, and ClinicalTrials.gov from 1 January 1990 through 16 November 2020.
STUDY SELECTION
Comparative studies of interventions of interest reporting critical or important outcomes, and larger single-group studies to evaluate prevalence of colonoscopy findings and harms.
DATA EXTRACTION
6 researchers extracted study data and risk of bias. The team assessed strength of evidence.
DATA SYNTHESIS
19 studies evaluated colonoscopy. Risk for prevalent colorectal cancer (CRC) compared with the general population is unclear. Based on low-strength evidence, long-term CRC diagnosis is similar with or without colonoscopy. High-strength evidence indicates that risk for prevalent CRC is higher among patients with complicated diverticulitis and colonoscopy complications are rare. Based on high-strength evidence, mesalamine does not reduce recurrence risk (6 randomized controlled trials [RCTs]). Evidence on other nonsurgical interventions is insufficient. For patients with prior complicated or smoldering or frequently recurrent diverticulitis, elective surgery is associated with reduced recurrence (3 studies; high strength). In 19 studies, serious surgical complications were uncommon.
LIMITATIONS
Few RCTs provided evidence. Heterogeneity of treatment effect was not adequately assessed.
CONCLUSION
It is unclear whether patients with recent acute diverticulitis are at increased risk for prevalent CRC, but those with complicated diverticulitis are at increased risk. Mesalamine is ineffective in preventing recurrence; other nonsurgical treatments have inadequate evidence. Elective surgery reduces recurrence in patients with prior complicated or smoldering or frequently recurrent diverticulitis, but it is unclear which of these patients may benefit most.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality and American College of Physicians. (PROSPERO: CRD42020151246).
Topics: Colonoscopy; Diverticulitis; Diverticulitis, Colonic; Humans; Mesalamine; United States
PubMed: 35038269
DOI: 10.7326/M21-1646 -
Cureus Mar 2021Inflammatory bowel disease (IBD) is a chronic condition of the bowel that can be further categorized into ulcerative colitis and Crohn's disease. Rarely, this condition... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic condition of the bowel that can be further categorized into ulcerative colitis and Crohn's disease. Rarely, this condition can be associated with pericarditis, which can be an extraintestinal manifestation of the disease or drug-induced. This review aims to determine the pathogenesis and management of pericarditis in IBD. In this review, the goal is to elucidate the pathogenesis of pericarditis in IBD and determine if pericarditis is an extraintestinal manifestation of IBD or a complication of current drug therapy used to manage IBD. Additionally, this review intends to explain the first-line management of pericarditis in IBD and explore the role of biologicals in attenuating pericarditis. An electronic search was conducted to identify relevant reports of pericarditis in IBD, and a quality assessment was conducted to identify high-quality articles according to the inclusion criteria. Full-text articles from inception to November 2020 were included, while non-English articles, gray literature, and animal studies were excluded. The majority of studies suggest that pericarditis arises as a complication of drug therapy by 5-aminosalicylic acid derivatives such as sulfasalazine, mesalamine, and balsalazide, and it occurs due to IgE-mediated allergic reactions, direct cardiac toxicity, cell-mediated hypersensitivity reactions, and humoral antibody response to therapy. Drug cessation or the initiation of a corticosteroid regimen seems to be the most effective means of managing pericarditis in IBD due to drug therapy or an extraintestinal manifestation.
PubMed: 33884251
DOI: 10.7759/cureus.14010 -
The Cochrane Database of Systematic... May 2022Antibiotics have been considered to treat ulcerative colitis (UC) due to their antimicrobial properties against intestinal bacteria linked to inflammation. However,... (Review)
Review
BACKGROUND
Antibiotics have been considered to treat ulcerative colitis (UC) due to their antimicrobial properties against intestinal bacteria linked to inflammation. However, there are concerns about their efficacy and safety.
OBJECTIVES
To determine whether antibiotic therapy is safe and effective for the induction and maintenance of remission in people with UC.
SEARCH METHODS
We searched five electronic databases on 10 December 2021 for randomised controlled trials (RCTs) comparing antibiotic therapy to placebo or an active comparator.
SELECTION CRITERIA
We considered people with UC of all ages, treated with antibiotics of any type, dose, and route of administration for inclusion. Induction studies required a minimum duration of two weeks for inclusion. Maintenance studies required a minimum duration of three months to be considered for inclusion.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcome for induction studies was failure to achieve remission and for maintenance studies was relapse, as defined by the primary studies.
MAIN RESULTS
We included 12 RCTs (847 participants). One maintenance of remission study used sole antibiotic therapy compared with 5-aminosalicylic acid (5-ASA). All other trials used concurrent medications or standard care regimens and antibiotics as an adjunct therapy or compared antibiotics with other adjunct therapies to examine the effect on induction of remission. There is high certainty evidence that antibiotics (154/304 participants) compared to placebo (175/304 participants) result in no difference in failure to achieve clinical remission (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.06). A subgroup analysis found no differences when steroids, steroids plus 5-ASA, or steroids plus 5-ASA plus probiotics were used as additional therapies to antibiotics and placebo. There is low certainty evidence that antibiotics (102/168 participants) compared to placebo (121/175 participants) may result in no difference in failure to achieve clinical response (RR 0.75, 95% CI 0.47 to 1.22). A subgroup analysis found no differences when steroids or steroids plus 5-ASA were used as additional therapies to antibiotics and placebo. There is low certainty evidence that antibiotics (6/342 participants) compared to placebo (5/349 participants) may result in no difference in serious adverse events (RR 1.19, 95% CI 0.38 to 3.71). A subgroup analysis found no differences when steroids were additional therapies to antibiotics and placebo. There is low certainty evidence that antibiotics (3/342 participants) compared to placebo (1/349 participants) may result in no difference in withdrawals due to adverse events (RR 2.06, 95% CI 0.27 to 15.72). A subgroup analysis found no differences when steroids or steroids plus 5-ASA were additional therapies to antibiotics and placebo. It is unclear if there is any difference between antibiotics in combination with probiotics compared to no treatment or placebo for failure to achieve clinical remission (RR 0.68, 95% CI 0.39 to 1.19), serious adverse events (RR 1.00, 95% CI 0.07 to 15.08), or withdrawals due to adverse events (RR 1.00, 95% CI 0.07 to 15.08). The certainty of the evidence is very low. It is unclear if there is any difference between antibiotics compared to 5-ASA for failure to achieve clinical remission (RR 2.20, 95% CI 1.17 to 4.14). The certainty of the evidence is very low. It is unclear if there is any difference between antibiotics compared to probiotics for failure to achieve clinical remission (RR 0.47, 95% CI 0.23 to 0.94). The certainty of the evidence is very low. It is unclear if there is any difference between antibiotics compared to 5-ASA for failure to maintain clinical remission (RR 0.71, 95% CI 0.47 to 1.06). The certainty of the evidence is very low. It is unclear if there is any difference between antibiotics compared to no treatment for failure to achieve clinical remission in a mixed population of people with active and inactive disease (RR 0.56, 95% CI 0.29 to 1.07). The certainty of the evidence is very low. For all other outcomes, no effects could be estimated due to a lack of data.
AUTHORS' CONCLUSIONS
There is high certainty evidence that there is no difference between antibiotics and placebo in the proportion of people who achieve clinical remission at the end of the intervention period. However, there is evidence that there may be a greater proportion of people who achieve clinical remission and probably a greater proportion who achieve clinical response with antibiotics when compared with placebo at 12 months. There may be no difference in serious adverse events or withdrawals due to adverse events between antibiotics and placebo. No clear conclusions can be drawn for any other comparisons. A clear direction for future research appears to be comparisons of antibiotics and placebo (in addition to standard therapies) with longer-term measurement of outcomes. Additionally. As there were single studies of other head-to-head comparisons, there may be scope for future studies in this area.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Humans; Mesalamine; Remission Induction
PubMed: 35583095
DOI: 10.1002/14651858.CD013743.pub2 -
The Cochrane Database of Systematic... Oct 2015Corticosteroids are first-line therapy for induction of remission in ulcerative colitis. Although corticosteroids may improve symptoms, they have significant adverse... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corticosteroids are first-line therapy for induction of remission in ulcerative colitis. Although corticosteroids may improve symptoms, they have significant adverse effects. Steroids which act topically, with less systemic side-effects may be more desirable. Budesonide is a topically acting corticosteroid with extensive first pass hepatic metabolism. There are currently three formulations of budesonide: two standard formulations including a controlled-ileal release capsule and a pH-dependent capsule both designed to release the drug in the distal small intestine and right colon; and the newer Budesonide-MMX® capsule designed to release the drug throughout the entire colon.
OBJECTIVES
The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in ulcerative colitis.
SEARCH METHODS
We searched MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Group Specialised Register from inception to April 2015. We also searched reference lists of articles, conference proceedings and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials comparing oral budesonide to placebo or another active therapy for induction of remission in ulcerative colitis were considered eligible. There were no exclusions based on patient age or the type, dose, duration or formulation of budesonide therapy.
DATA COLLECTION AND ANALYSIS
Two independent investigators reviewed studies for eligibility, extracted data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome was induction of remission (as defined by the primary studies) at week eight. Secondary outcomes included clinical, endoscopic and histologic improvement, adverse events and early withdrawal. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome and the mean difference (MD) and corresponding 95% CI for each continuous outcome. Data were analysed on an intention-to-treat basis.
MAIN RESULTS
Six studies (1808 participants) were included. Four studies compared budesonide-MMX® with placebo, one small pilot study looked at clinical remission at week four, and was subsequently followed by three large, studies that assessed combined clinical and endoscopic remission at week eight. Although two placebo-controlled studies had mesalamine and Entocort (standard budesonide) treatment arms, these studies were not sufficiently powered to compare Budesonide-MMX® with these active comparators. One small study compared standard budesonide with prednisolone and one study compared standard budesonide to mesalamine. Four studies were rated as low risk of bias and two studies had an unclear risk of bias. A pooled analysis of three studies (900 participants) showed that budesonide-MMX® 9 mg was significantly superior to placebo for inducing remission (combined clinical and endoscopic remission) at 8 weeks. Fifteen per cent (71/462) of budesonide-MMX® 9 mg patients achieved remission compared to 7% (30/438) of placebo patients (RR 2.25, 95% CI 1.50 to 3.39). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (101 events). A subgroup analysis by concurrent mesalamine use suggests higher efficacy in the 442 patients who were not considered to be mesalamine-refractory (RR 2.89, 95% CI 1.59 to 5.25). A subgroup analysis by disease location suggests budesonide is most effective in patients with left-sided disease (RR 2.98, 95% CI 1.56 to 5.67; 289 patients). A small pilot study reported no statistically significant difference in endoscopic remission between budesonide and prednisolone (RR 0.75, 95% CI 0.23 to 2.42; 72 patients). GRADE indicated that the overall quality of the evidence supporting this outcome was very low due to unclear risk of bias and very sparse data (10 events). Standard oral budesonide was significantly less likely to induce clinical remission than oral mesalamine after 8 weeks of therapy (RR 0.72, 95% CI 0.57 to 0.91; 1 study, 343 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (161 events). Another study found no difference in remission rates between budesonide-MMX® 9 mg and mesalamine (RR 1.48, 95% CI 0.81 to 2.71; 247 patients). GRADE indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (37 events). One study found no difference in remission rates between budesonide-MMX® 9 mg and standard budesonide 9 mg (RR 1.38, 95% CI 0.72 to 2.65; 212 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (32 events). Suppression of plasma cortisol was more common in prednisolone-treated patients (RR 0.02, 95% CI 0.0 to 0.33). While budesonide does appear to suppress morning cortisol to some extent, mean morning cortisol values remained within the normal range in 2 large studies (n = 899) and there was no difference in glucocorticoid-related side-effects across different treatment groups. Further, study withdrawal due to adverse events was not more common in budesonide compared with placebo treated patients (RR 0.85, 95% CI 0.53 to 1.38). Common adverse events included worsening ulcerative colitis, headache, pyrexia, insomnia, back pain, nausea, abdominal pain, diarrhoea, flatulence and nasopharyngitis.
AUTHORS' CONCLUSIONS
Moderate quality evidence to supports the use of oral budesonide-MMX® at a 9 mg daily dose for induction of remission in active ulcerative colitis, particularly in patients with left-sided colitis. Budesonide-MMX® 9 mg daily is effective for induction of remission in the presence or absence of concurrent 5-ASA therapy. Further, budesonide-MMX® appears to be safe, and does not lead to significant impairment of adrenocorticoid function compared to placebo. Moderate quality evidence from a single study suggests that mesalamine may be superior to standard budesonide for the treatment of active ulcerative colitis. Low quality evidence from one study found no difference in remission rates between budesonide MMX® and mesalamine. Very low quality evidence from one small study showed no difference in endoscopic remission rates between standard budesonide and prednisolone. Low quality evidence from one study showed no difference in remission rates between budesonide-MMX® and standard budesonide. Adequately powered studies are needed to allow conclusions regarding the comparative efficacy and safety of budesonide versus prednisolone, budesonide-MMX® versus standard budesonide and budesonide versus mesalamine.
Topics: Administration, Oral; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colitis, Ulcerative; Humans; Induction Chemotherapy; Mesalamine; Prednisone; Randomized Controlled Trials as Topic
PubMed: 26497719
DOI: 10.1002/14651858.CD007698.pub3 -
United European Gastroenterology Journal Oct 2022We performed a systematic review to investigate the definition of mild to moderate active ulcerative colitis (UC), and to describe predictors of good response to... (Review)
Review
We performed a systematic review to investigate the definition of mild to moderate active ulcerative colitis (UC), and to describe predictors of good response to treatment in clinical trials assessing 5-ASA and/or budesonide. Thirty-nine randomized controlled trials were included. The UC Disease Activity Index (UCDAI) was the most frequent score used for defining mild to moderate active UC (16 studies, 41%), followed by Clinical Activity Index in 11 studies (28.2%). Four different cut-offs were used to define mild to moderate active UC using the UCDAI. The most frequently reported predictors of good response to treatment was a mild and moderate disease activity. There is heterogeneity in the definition of mild to moderate active UC in randomized clinical trials. A standardized definition of mild to moderate active UC used for inclusion of patients in clinical trials is needed.
Topics: Budesonide; Colitis, Ulcerative; Humans; Mesalamine
PubMed: 36029157
DOI: 10.1002/ueg2.12283 -
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 -
The Cochrane Database of Systematic... Aug 2015Methotrexate, a folate antagonist, is an immunosuppressant drug that is effective for treating several inflammatory disorders including Crohn's disease. Ulcerative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Methotrexate, a folate antagonist, is an immunosuppressant drug that is effective for treating several inflammatory disorders including Crohn's disease. Ulcerative colitis, a related chronic inflammatory bowel disease, can be challenging to treat. T his updated systematic review summarizes the current evidence on the use of methotrexate for induction maintenance of remission in ulcerative colitis.
OBJECTIVES
The objectives of this review were to assess the efficacy and safety of methotrexate for maintenance of remission in patients with ulcerative colitis.
SEARCH METHODS
We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD/FBD group specialized trials register from inception to June 26, 2014. Study references and review papers were also searched for additional trials. Abstracts from major gastroenterological meetings were searched to identify research published in abstract form only.
SELECTION CRITERIA
Randomized controlled trials in which methotrexate was compared to placebo or an active comparator in patients with quiescent ulcerative were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias for each study. The primary outcome was the occurrence of clinical or endoscopic relapse as defined by the primary studies. Secondary outcomes included frequency and nature of adverse events, change of disease activity score and steroid-sparing effect. We calculated the risk ratio and corresponding 95% confidence interval for dichotomous outcomes. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria.
MAIN RESULTS
Three trials (165 patients) fulfilled the inclusion criteria. One study compared oral methotrexate (12.5 mg/week) to placebo, another compared oral methotrexate (15 mg/week) to 6-mercaptopurine (6-MP, 1.5 mg/kg/day) or 5-aminosalicylic acid (5-ASA, 3 g/day) and the other compared methotrexate (15 mg/week) in combination sulfasalazine (3 g/day) to sulfasalazine. The placebo-controlled study was rated as low risk of bias. The study comparing methotrexate to 6-MP and 5-ASA was rated as high risk of bias and the study assessing methotrexate and sulfasalazine was rated as unclear risk of bias for sequence generation, allocation concealment and blinding. The placebo-controlled study found no statistically significant differences in the proportion of patients who maintained remission. At nine months, 36% (5/14) of methotrexate patients maintained remission compared to 54% (10/18) of placebo patients (RR 0.64, 95% CI 0.28 to 1.45). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to very sparse data (15 events). The study comparing combination therapy to sulfasalazine found no statistically significant difference in the proportion of patients who maintained remission. At 12 months, 100% (14/14) of patients in the combination group maintained remission compared to 75% (9/12) of sulfasalazine patients (RR 1.32, 95% CI 0.94 to 0.86), A GRADE analysis indicated that the overall quality of the evidence for this outcome was very low due to unknown risk of bias and very sparse data (23 events). There were no statistically significant differences in maintenance of remission rates between methotrexate and 6-MP or between methotrexate and 5-ASA. At 76 weeks, 14% (1/7) of methotrexate patients maintained remission compared to 64% (7/11) of 6-MP patients (RR 0.22, 95% CI 0.03 to 1.45) and 0% (0/2) of 5-ASA patients (RR 1.13, 95% CI 0.06 to 20.71). A GRADE analysis indicated that the overall quality of the evidence from this study was very low due to high risk of bias and very sparse data. Adverse events reported in these studies included transient leucopenia, migraine, nausea and dyspepsia, mild alopecia, mild increase in aspartate aminotransferase levels, peritoneal abscess, hypoalbuminemia, severe rash and atypical pneumonia
AUTHORS' CONCLUSIONS
The results for efficacy and safety outcomes between methotrexate and placebo, methotrexate and sulfasalazine, methotrexate and 6-mercaptopurine and methotrexate and 5-aminosalicylic acid were uncertain. Whether a higher dose or parenteral administration of methotrexate would be effective in quiescent ulcerative colitis is unknown. At present there is no evidence supporting the use of methotrexate for maintenance of remission in ulcerative colitis. More studies are needed to determine the efficacy and safety of methotrexate maintenance therapy in patients with quiescent ulcerative colitis. Large scale methodologically rigorous randomized controlled trials are needed. These studies should investigate higher doses of methotrexate (e.g. 15 to 25 mg/week) and parenteral administration.
Topics: Administration, Oral; Colitis, Ulcerative; Humans; Immunosuppressive Agents; Maintenance Chemotherapy; Mercaptopurine; Mesalamine; Methotrexate; Sulfasalazine
PubMed: 26263042
DOI: 10.1002/14651858.CD007560.pub3 -
World Journal of Clinical Cases Sep 2020A previously healthy 22-year-old woman presented with abdominal pain and jaundice. She had a reagent antinuclear factor (1:640, with a homogeneous nuclear pattern) and...
BACKGROUND
A previously healthy 22-year-old woman presented with abdominal pain and jaundice. She had a reagent antinuclear factor (1:640, with a homogeneous nuclear pattern) and hypergammaglobulinemia (2.16 g/dL). Anti-smooth muscle, anti-mitochondrial and anti-liver-kidney microsomal antibody type 1 antibodies were negative. Magnetic resonance cholangiography showed a cirrhotic liver with multiple focal areas of strictures of the intrahepatic bile ducts, with associated dilations. Liver biopsy demonstrated periportal necroinflammatory activity, plasmocyte infiltration and advanced fibrosis. Colonoscopy showed ulcerative pancolitis and mild activity (Mayo score 1), with a spared rectum. Treatment with corticosteroids, azathioprine, ursodeoxycholic acid and mesalamine was initiated, with improvement in laboratory tests. The patient was referred for a liver transplantation evaluation.
AIM
To report the case of a female patient with autoimmune hepatitis and primary sclerosing cholangitis (PSC) overlap syndrome associated with ulcerative colitis and to systematically review the available cases of autoimmune hepatitis and PSC overlap syndrome.
METHODS
In accordance with preferred reporting items for systematic reviews and meta-analysis protocols guidelines, retrieval of studies was based on medical subject headings and health sciences descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), Biblioteca Regional de Medicina, Latin American and Caribbean Health Sciences Literature, Cochrane Library for Systematic Reviews and Opengray.eu. Languages were restricted to English, Spanish and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually.
RESULTS
The search strategy retrieved 3349 references. In the final analysis, 44 references were included, with a total of 109 cases reported. The most common clinical finding was jaundice and 43.5% of cases were associated with inflammatory bowel disease. Of these, 27.6% were cases of Crohn's disease, 68% of ulcerative colitis, and 6.4% of indeterminate colitis. Most patients were treated with steroids. All-cause mortality was 3.7%.
CONCLUSION
PSC and autoimmune hepatitis overlap syndrome is generally associated with inflammatory bowel disease and has low mortality and good response to treatment.
PubMed: 33024765
DOI: 10.12998/wjcc.v8.i18.4075 -
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