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The Cochrane Database of Systematic... Aug 2020Oral 5-aminosalicylic acid (5-ASA; also known as mesalazine or mesalamine) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral 5-aminosalicylic acid (5-ASA; also known as mesalazine or mesalamine) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. In an earlier version of this review, we found that 5-ASA drugs were more effective than placebo for maintenance of remission of ulcerative colitis (UC), but had a significant therapeutic inferiority relative to SASP. In this version, we have rerun the search to bring the review up to date.
OBJECTIVES
To assess the efficacy, dose-responsiveness, and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent UC and to compare the efficacy and safety of once-daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens.
SEARCH METHODS
We performed a literature search for studies on 11 June 2019 using MEDLINE, Embase, and the Cochrane Library. In addition, we searched review articles and conference proceedings.
SELECTION CRITERIA
We included randomized controlled trials with a minimum treatment duration of six months. We considered studies of oral 5-ASA therapy for treatment of participants with quiescent UC compared with placebo, SASP, or other 5-ASA formulations. We also included studies that compared once-daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose-ranging studies.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes were adherence, adverse events (AE), serious adverse events (SAE), withdrawals due to AEs, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus SASP, once-daily dosing versus conventional dosing, 5-ASA (balsalazide, Pentasa, and olsalazine) versus comparator 5-ASA formulation (Asacol and Salofalk), and 5-ASA dose-ranging. We calculated the risk ratio (RR) and 95% confidence interval (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
The search identified 44 studies (9967 participants). Most studies were at low risk of bias. Ten studies were at high risk of bias. Seven of these studies were single-blind and three were open-label. 5-ASA is more effective than placebo for maintenance of clinical or endoscopic remission. About 37% (335/907) of 5-ASA participants relapsed at six to 12 months compared to 55% (355/648) of placebo participants (RR 0.68, 95% CI 0.61 to 0.76; 8 studies, 1555 participants; high-certainty evidence). Adherence to study medication was not reported for this comparison. SAEs were reported in 1% (6/550) of participants in the 5-ASA group compared to 2% (5/276) of participants in the placebo group at six to 12 months (RR 0.60, 95% CI 0.19 to 1.84; 3 studies, 826 participants; low-certainty evidence). There is probably little or no difference in AEs at six to 12 months' follow-up (RR 0.93, 95% CI 0.73 to 1.18; 5 studies, 1132 participants; moderate-certainty evidence). SASP is more effective than 5-ASA for maintenance of remission. About 48% (416/871) of 5-ASA participants relapsed at six to 18 months compared to 43% (336/784) of SASP participants (RR 1.14, 95% CI 1.03 to 1.27; 12 studies, 1655 participants; high-certainty evidence). Adherence to study medication and SAEs were not reported for this comparison. There is probably little or no difference in AEs at six to 12 months' follow-up (RR 1.07, 95% CI 0.82 to 1.40; 7 studies, 1138 participants; moderate-certainty evidence). There is little or no difference in clinical or endoscopic remission rates between once-daily and conventionally dosed 5-ASA. About 37% (717/1939) of once-daily participants relapsed over 12 months compared to 39% (770/1971) of conventional-dosing participants (RR 0.94, 95% CI 0.88 to 1.01; 10 studies, 3910 participants; high-certainty evidence). There is probably little or no difference in medication adherence rates. About 10% (106/1152) of participants in the once-daily group failed to adhere to their medication regimen compared to 8% (84/1154) of participants in the conventional-dosing group (RR 1.18, 95% CI 0.72 to 1.93; 9 studies, 2306 participants; moderate-certainty evidence). About 3% (41/1587) of participants in the once-daily group experienced a SAE compared to 2% (35/1609) of participants in the conventional-dose group at six to 12 months (RR 1.20, 95% CI 0.77 to 1.87; moderate-certainty evidence). There is little or no difference in the incidence of AEs at six to 13 months' follow-up (RR 0.98, 95% CI 0.92 to 1.04; 8 studies, 3497 participants; high-certainty evidence). There may be little or no difference in the efficacy of different 5-ASA formulations. About 44% (158/358) of participants in the 5-ASA group relapsed at six to 18 months compared to 41% (142/349) of participants in the 5-ASA comparator group (RR 1.08, 95% CI 0.91 to 1.28; 6 studies, 707 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
There is high-certainty evidence that 5-ASA is superior to placebo for maintenance therapy in UC. There is high-certainty evidence that 5-ASA is inferior compared to SASP. There is probably little or no difference between 5-ASA and placebo, and 5-ASA and SASP in commonly reported AEs such as flatulence, abdominal pain, nausea, diarrhea, headache, and dyspepsia. Oral 5-ASA administered once daily has a similar benefit and harm profile as conventional dosing for maintenance of remission in quiescent UC.
Topics: Administration, Oral; Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Bias; Colitis, Ulcerative; Drug Administration Schedule; Humans; Maintenance Chemotherapy; Medication Adherence; Mesalamine; Patient Dropouts; Placebos; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Sulfasalazine
PubMed: 32856298
DOI: 10.1002/14651858.CD000544.pub5 -
Journal of Crohn's & Colitis May 2024Patients with inflammatory bowel disease [IBD] have a more than two fold higher risk of venous thromboembolic events [VTE] than the general population. The aetiology is... (Meta-Analysis)
Meta-Analysis
Anti-tumor Necrosis Factor Alpha Versus Corticosteroids: A 3-fold Difference in the Occurrence of Venous Thromboembolism in Inflammatory Bowel Disease-A Systematic Review and Meta-analysis.
BACKGROUND AND AIMS
Patients with inflammatory bowel disease [IBD] have a more than two fold higher risk of venous thromboembolic events [VTE] than the general population. The aetiology is complex, and the role of medication is not precisely defined. We aimed to assess the effects of anti-tumor necrosis factor alpha [anti-TNFα] drugs and conventional anti-inflammatory therapy, namely corticosteroids [CS], immunomodulators [IM], and 5-aminosalicylates [5-ASA] on VTE in IBD.
METHODS
A systematic search was performed in five databases on November 22, 2022. We included studies reporting VTE in the distinct categories of medications, determined the proportions, and calculated the odds ratios [OR] with 95% confidence intervals [CI], using the random-effects model. The risk of bias was evaluated with the Joanna Briggs Institute Critical Appraisal Checklist and the Risk of Bias in Non-randomized Studies of Interventions tool.
RESULTS
The quantitative analysis included 16 observational studies, with data from 91 322 IBD patients. Patients receiving anti-TNFα medication had significantly less VTE [proportion: 0.05, CI: 0.02-0.10], than patients treated with CS [proportion: 0.16, CI: 0.07-0.32], with OR = 0.42 [CI: 0.25-0.71]. IMs resulted in similar proportions of VTE compared with biologics [0.05, CI: 0.03-0.10], with OR = 0.94 [CI: 0.67-1.33]. The proportion of patients receiving 5-ASA having VTE was 0.09 [CI: 0.04-0.20], with OR = 1.00 [CI: 0.61-1.62].
CONCLUSIONS
Biologics should be preferred over corticosteroids in cases of severe flare-ups and multiple VTE risk factors, as they are associated with reduced odds of these complications. Further studies are needed to validate our data.
Topics: Humans; Venous Thromboembolism; Inflammatory Bowel Diseases; Adrenal Cortex Hormones; Tumor Necrosis Factor-alpha; Mesalamine
PubMed: 37952112
DOI: 10.1093/ecco-jcc/jjad193 -
Alimentary Pharmacology & Therapeutics Aug 2017Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis.
AIM
To perform a systematic review and meta-analysis to examine the efficacy of probiotics in IBD.
METHODS
MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (until November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs).
RESULTS
The search identified 12 253 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission=0.86; 95% CI=0.68-1.08). However, when only trials of VSL#3 were considered there appeared to be a benefit (RR=0.74; 95% CI=0.63-0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR=1.02; 95% CI=0.85-1.23). There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing relapse of CD after surgically induced remission.
CONCLUSIONS
VSL#3 may be effective in inducing remission in active UC. Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. The efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known.
Topics: Adult; Colitis, Ulcerative; Crohn Disease; Humans; Mesalamine; Probiotics; Randomized Controlled Trials as Topic; Remission Induction; Secondary Prevention; Treatment Outcome
PubMed: 28653751
DOI: 10.1111/apt.14203 -
The Cochrane Database of Systematic... Oct 2017Diverticular disease is a common condition that increases in prevalence with age. Recent theories on the pathogenesis of diverticular inflammation have implicated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diverticular disease is a common condition that increases in prevalence with age. Recent theories on the pathogenesis of diverticular inflammation have implicated chronic inflammation similar to that seen in ulcerative colitis. Mesalamine, or 5-aminosalicylic acid (5-ASA), is a mainstay of therapy for individuals with ulcerative colitis. Accordingly, 5-ASA has been studied for prevention of recurrent diverticulitis.
OBJECTIVES
To evaluate the efficacy of mesalamine (5-ASA) for prevention of recurrent diverticulitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), in the Cochrane Library; Ovid MEDLINE (from 1950 to 9 September 2017); Ovid Embase (from 1974 to 9 September 2017); and two clinical trials registries for ongoing trials - Clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform database (9 September 2017).We also searched proceedings from major gastrointestinal conferences - Digestive Disease Week (DDW), United European Gastroenterology Week (UEGW), and the American College of Gastroenterology (ACG) Annual Scientific Meeting - from 2010 to September 2017. In addition, we scanned reference lists from eligible publications, and we contacted corresponding authors to ask about additional trials.
SELECTION CRITERIA
We included randomised controlled clinical trials comparing the efficacy of 5-ASA versus placebo or another active drug for prevention of recurrent diverticulitis.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as defined by Cochrane. Three review authors assessed eligibility for inclusion. Two review authors selected studies, extracted data, and assessed methodological quality independently. We calculated risk ratios (RRs) for prevention of diverticulitis recurrence using an intention-to-treat principle and random-effects models. We assessed heterogeneity using criteria for Chi (P < 0.10) and I tests (> 50%). To explore sources of heterogeneity, we conducted a priori subgroup analyses. To assess the robustness of our results, we carried out sensitivity analyses using different summary statistics (RR vs odds ratio (OR)) and meta-analytical models (fixed-effect vs random-effects).
MAIN RESULTS
We included in this review seven studies with a total of 1805 participants. We judged all seven studies to have unclear or high risk of bias. Investigators found no evidence of an effect when comparing 5-ASA versus control for prevention of recurrent diverticulitis (31.3% vs 29.8%; RR 0.69, 95% confidence interval (CI) 0.43 to 1.09); very low quality of evidence).Five of the seven studies provided data on adverse events of 5-ASA therapy. The most commonly reported side effects were gastrointestinal symptoms (epigastric pain, nausea, and diarrhoea). No significant difference was seen between 5-ASA and control (67.8% vs 64.6%; RR 0.98, 95% CI 0.91 to 1.06; P = 0.63; moderate quality of evidence), nor was significant heterogeneity observed (I = 0%; P = 0.50).
AUTHORS' CONCLUSIONS
The effects of 5-ASA on recurrence of diverticulitis are uncertain owing to the small number of heterogenous trials included in this review. Rates of recurrent diverticulitis were similar among participants using 5-ASA and control participants. Effective medical strategies for prevention of recurrent diverticulitis are needed, and further randomised, double-blinded, placebo-controlled trials of rigorous design are warranted to specify the effects of 5-ASA (mesalamine) in the management of diverticulitis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diverticulitis, Colonic; Humans; Mesalamine; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 28973845
DOI: 10.1002/14651858.CD009839.pub2 -
Digestive Diseases (Basel, Switzerland) 20135-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of therapy in inflammatory bowel disease (IBD). Intestinal inflammation is the main risk factor for... (Review)
Review
5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of therapy in inflammatory bowel disease (IBD). Intestinal inflammation is the main risk factor for colorectal cancer (CRC) in IBD. Hence, all drugs that are able to induce and maintain mucosal healing (MH) may prevent CRC risk in IBD. In patients with mild to moderate ulcerative colitis (UC), a recent systematic review of 5-ASA trials demonstrated that MH was achieved in nearly 50% of patients. A systematic review including 48 studies linked 5-ASA chemopreventive properties to five distinct pathways: cell cycle progression, scavenging of reactive oxygen- or nitrogen-derived metabolites, TNF-α/TGF-ss signaling, WNT/β-catenin signaling and antibacterial properties. Therefore, in addition to their overall anti-inflammatory activity on the intestinal mucosa, 5-ASA compounds have specific effects on colorectal carcinogenesis at the molecular level. In 2005, a landmark meta-analysis of observational studies found a protective association between 5-ASA and CRC or a combined end point of CRC/dysplasia in UC patients. More recently, a meta-analysis failed to identify a protective effect of 5-ASA on CRC risk in non-referral populations, but in a separate analysis of 9 clinic-based studies, the pooled odds ratio was 0.58 (95% confidence interval: 0.45-0.75), further highlighting the chemopreventive effect of 5-ASA on CRC risk. In conclusion, 5-ASA therapy may reduce CRC risk by healing the mucosa of UC patients and via specific mechanisms of action at the molecular level. Conducting a clinical trial providing the best level of evidence by comparing UC patients receiving 5-ASA treatment versus those included in a placebo arm would be unethical.
Topics: Chemoprevention; Colorectal Neoplasms; Evidence-Based Medicine; Humans; Inflammatory Bowel Diseases; Mesalamine; Risk Factors
PubMed: 24030235
DOI: 10.1159/000353806 -
Inflammatory Bowel Diseases May 2007Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylic acid (5-ASA). Studies with 5-ASA treatment in... (Review)
Review
Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylic acid (5-ASA). Studies with 5-ASA treatment in which serum creatinine or creatinine clearance was measured regularly show that nephrotoxicity is exceptional (mean rate of only 0.26% per patient-year). There have been several case reports, including 46 patients, of renal disease associated with 5-ASA treatment in patients with IBD. 5-ASA treatment-related nephrotoxicity is reported most often within the first 12 months, but also delayed presentation after several years has been shown. The absence of a clear relationship between 5-ASA dose and the risk of nephrotoxicity suggests that this complication is idiosyncratic rather than dose-related. Most of the patients with renal disease associated with 5-ASA treatment suffered interstitial nephritis, with symptoms and signs being nonspecific, which may delay detection for many months. The nephrotoxicity potential of mesalazine and sulfasalazine seems to be similar. The risk with different oral preparations of 5-ASA is probably too small to influence the choice of agent. Mesalazine should be withdrawn when renal impairment manifests in a patient with IBD; if this does not result in a fall in serum creatinine, then renal biopsy should be considered. A trial of high-dose steroid may be recommended in patients whose renal function does not respond to drug withdrawal. The optimal monitoring schedule of serum creatinine in patients receiving 5-ASA treatment remains to be established, as there is no evidence to date that either the test, or the frequency of testing, improves patient outcomes.
Topics: Animals; Dose-Response Relationship, Drug; Humans; Inflammatory Bowel Diseases; Kidney; Kidney Diseases; Mesalamine; Nephritis, Interstitial
PubMed: 17243140
DOI: 10.1002/ibd.20099 -
Scientific Reports Apr 2017Topical 5-aminosalicylic acid (5-ASA) and corticosteroids are used frequently in the treatment of active distal ulcerative colitis (UC). Our study aimed to determine the... (Meta-Analysis)
Meta-Analysis
Topical 5-aminosalicylic acid (5-ASA) and corticosteroids are used frequently in the treatment of active distal ulcerative colitis (UC). Our study aimed to determine the efficacy and safety of different topical drugs used to treat active distal UC. A random-effects model within a Bayesian framework was utilized to compare treatment effects and safety as odds ratios (ORs) with corresponding 95% credible intervals (CrI). The surface under the cumulative ranking area (SUCRA) and median rank (MR) with corresponding 95% CrI were calculated to rank the treatment outcomes. In the induction of clinical and endoscopic remission, most regimens showed significant advantages over placebo except topical budesonide 0.5 mg/d and hydrocortisone 100 mg/d. According to SUCRA and MR values, rectal 5-ASA 1.5 to 2.0 g/d + Beclomethasone dipropionate (BDP) 3 mg/d rendered the highest probability of being the best regimen to achieve clinical and endoscopic remission, followed by the separate use of 5-ASA 4 g/d and BDP 3 mg/d. The occurrence of adverse events was not significantly different between each treatments and placebo. In conclusion, the combined use of topical 5-ASA and BDP proved to be the best choice for active distal UC and further well-designed researches are warranted to assess its efficacy and safety.
Topics: Administration, Rectal; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Humans; Mesalamine; Safety; Treatment Outcome
PubMed: 28440311
DOI: 10.1038/srep46693 -
International Journal of Colorectal... Sep 2012One of today's controversies remains the prevention of recurrent diverticulitis. Current guidelines advise a conservative approach, based on studies showing low... (Meta-Analysis)
Meta-Analysis Review
AIM AND BACKGROUND
One of today's controversies remains the prevention of recurrent diverticulitis. Current guidelines advise a conservative approach, based on studies showing low recurrence rates and a high operative morbidity and mortality. Conservative measures in prevention recurrence are dietary advises and medical therapies, including probiotics and 5-aminosalicylic acid.
OBJECTIVES
The aim of this systematic review is to assess whether medical or dietary therapies can prevent recurrent diverticulitis after a primary episode of acute diverticulitis. METHOD AND SEARCH STRATEGY: We searched different databases for papers published between January 1966 and January 2011.
STUDY SELECTION
Clinical studies were eligible for inclusion if they assessed the prevention of recurrent diverticulitis with a medical or dietary therapy. Exclusion criteria were studies without a control group.
RESULTS
Three randomized controlled trials (RCT), all with a Jadad quality score of 2 out of 5, were included in this systematic review. Mesalazine results in significantly less disease recurrence and fewer symptoms after an acute episode. The use of probiotics decreases symptoms but does not reduce recurrence. No difference in effect is seen when Balsalazide is added to probiotics compared to probiotics only. No relevant studies on dietary therapy/advices or antibiotics for prevention of recurrent diverticulitis were found.
CONCLUSION
The evidence that supports medical therapy to prevent recurrent diverticulitis is of poor quality. Treatment with 5-aminosalicylic acid seems promising. Based on current data, no recommendation of any non-operative relapse prevention therapy for diverticular disease can be made.
Topics: Anti-Bacterial Agents; Dietary Fiber; Diverticulitis; Humans; Mesalamine; Probiotics; Recurrence
PubMed: 22576905
DOI: 10.1007/s00384-012-1486-7 -
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 -
PloS One 2016Ulcerative colitis (UC) is a chronic and remitting inflammatory disease that is characterized by chronic idiopathic inflammation of the colon and bloody diarrhea.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ulcerative colitis (UC) is a chronic and remitting inflammatory disease that is characterized by chronic idiopathic inflammation of the colon and bloody diarrhea. Currently drug treatment is the main intervention for patients with mild to moderate UC. Mesalazine (5-ASA) and beclomethasone dipropionate (BDP) have been widely used for the treatment of UC and have yielded satisfactory results. This study compared the effectiveness of 5-ASA and BDP in the treatment of UC.
METHODS
The PubMed, Medline, SinoMed, Embase, and Cochrane Librinary databases were searched for eligible studies. Data were extracted by two of the coauthors independently and were analyzed using RevMan statistical software, version 5.3. Weighted mean differences (WMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool was used to assess the risk of bias.
RESULTS
Seven randomized controlled trials that compared BDP with 5-ASA in treating UC were identified as eligible. The methodological quality of the trials ranged from low to moderate. A pooled analysis of effectiveness based on the Disease Activity Index (DAI) or other assessment method after treatment revealed that in the treatment of UC, there are no obvious differences between BDP and 5-ASA in inducing remission and clinical improvement (OR = 0.76, 95% CI = 0.56-1.03, P = 0.08). The total numbers of adverse events associated with BDP and 5-ASA treatments for UC were similar (OR = 1.21, 95% CI = 0.71-2.09, P = 0.48). The safety profiles for these two drugs are good. According to subgroup-analysis, we found no obvious differences of clinical efficacy between BDP and 5-ASA no matter oral or enema administration was used in the treatment of UC. A sensitivity analysis demonstrated the stability of the pooled results.
CONCLUSION
During induction treatment of mild to moderate UC, there is no obvious difference between the two groups with respect to remission and clinical improvement. Given that the upper confidence limit for the OR barely exceeds 1.0 and that the p-value is close to 0.05 for this primary efficacy outcome as well as that the horizontal block lies to the left of the vertical line, it indicates that the clinical efficacy of BDP may be better than 5-ASA. However, taking into account that BDP has the risk of hypothalamic-pituitary-adrenal axis (HPA) suppression, 5-ASA has a potential advantage of safety in the treatment of mild to moderate UC.
Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Beclomethasone; Colitis, Ulcerative; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Humans; Mesalamine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27501314
DOI: 10.1371/journal.pone.0160500