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The Cochrane Database of Systematic... Oct 2016The results from controlled clinical trials investigating the efficacy of azathioprine and 6-mercaptopurine for the treatment of active Crohn's disease have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The results from controlled clinical trials investigating the efficacy of azathioprine and 6-mercaptopurine for the treatment of active Crohn's disease have been conflicting and controversial. An updated meta-analysis was performed to assess the effectiveness of these drugs for the induction of remission in active Crohn's disease.
OBJECTIVES
The primary objective was to determine the efficacy and safety of azathioprine and 6-mercaptopurine for induction of remission in active Crohn's disease.
SEARCH METHODS
We searched MEDLINE, EMBASE and the Cochrane Library from inception to 30 October 2015. Review articles and conference proceedings were also searched to identify additional studies.
SELECTION CRITERIA
Randomized controlled trials (RCTs) of oral azathioprine or 6-mercaptopurine compared to placebo or active therapy involving adult patients with active Crohn's disease were selected for inclusion.
DATA COLLECTION AND ANALYSIS
Data were extracted by two independent observers based on the intention-to-treat principle. Outcomes of interest included: clinical remission, clinical improvement, fistula improvement or healing, steroid sparing, adverse events, withdrawals due to adverse events and serious adverse events. We calculated the pooled relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting each outcome was assessed using the GRADE criteria.
MAIN RESULTS
Thirteen RCTs (n = 1211 patients) of azathioprine and 6-mercaptopurine therapy in adult patients were identified: nine included placebo comparators and six included active comparators. The majority of included studies were rated as low risk of bias. There was no statistically significant difference in clinical remission rates between azathioprine or 6-mercaptopurine and placebo. Forty-eight per cent (95/197) of patients receiving antimetabolites achieved remission compared to 37% (68/183) of placebo patients (5 studies, 380 patients; RR 1.23, 95% CI 0.97 to 1.55). There was no statistically significant difference in clinical improvement rates between azathioprine or 6-mercaptopurine and placebo. Forty-eight per cent (107/225) of patients receiving antimetabolites achieved clinical improvement or remission compared to 36% (75/209) of placebo patients (8 studies, 434 patients; RR 1.26, 95% CI 0.98 to 1.62). There was a statistically significant difference in steroid sparing (defined as prednisone dose < 10 mg/day while maintaining remission) between azathioprine and placebo. Sixty-four per cent (47/163) of azathioprine patients were able to reduce their prednisone dose to < 10 mg/day compared to 46% (32/70) of placebo patients (RR 1.34, 95% CI 1.02 to 1.77). GRADE analyses rated the overall quality of the evidence for the outcomes clinical remission, clinical improvement and steroid sparing as moderate due to sparse data. There was no statistically significant difference in withdrawals due to adverse events or serious adverse events between antimetabolites and placebo. Ten percent of patients in the antimetabolite group withdrew due to adverse events compared to 5% of placebo patients (8 studies, 510 patients; RR 1.70, 95% CI 0.94 to 3.08). Serious adverse events were reported in 14% of patients receiving azathioprine compared to 4% of placebo patients (2 studies, 216 patients; RR 2.57, 95% CI 0.92 to 7.13). Common adverse events reported in the placebo controlled studies included: allergic reactions. leukopenia, pancreatitis and nausea. Azathioprine was significantly inferior to infliximab for induction of steroid-free clinical remission. Thirty per cent (51/170) of azathioprine patients achieved steroid-free remission compared to 44% (75/169) of infliximab patients (1 study, 339 patients; RR 0.68, 95% CI 0.51 to 0.90). The combination of azathioprine and infliximab was significantly superior to infliximab alone for induction of steroid-free clinical remission. Sixty per cent (116/194) of patients in the combined azathioprine and infliximab group achieved steroid-free remission compared to 48% (91/189) of infliximab patients (2 studies, 383 patients; RR 1.23, 95% CI 1.02 to 1.47). Azathioprine or 6-mercaptopurine therapy was found to be no better at inducing steroid free clinical remission compared to methotrexate (RR 1.13, 95% CI 0.85 to 1.49) and 5-aminosalicylate or sulfasalazine (RR 1.24, 95% CI 0.80 to 1.91). There were no statistically significant differences in withdrawals due to adverse events between azathioprine or 6-mercaptopurine and methotrexate (RR 0.78, 95% CI 0.23 to 2.71); between azathioprine or 6-mercaptopurine and 5-aminosalicylate or sulfasalazine (RR 0.98, 95% CI 0.38 to 2.54); between azathioprine and infliximab (RR 1.47, 95% CI 0.96 to 2.23); or between the combination of azathioprine and infliximab and infliximab (RR 1.16, 95% CI 0.75 to 1.80). Common adverse events in the active comparator trials included nausea, abdominal pain, pyrexia and headache.
AUTHORS' CONCLUSIONS
Azathioprine and 6-mercaptopurine offer no advantage over placebo for induction of remission or clinical improvement in active Crohn's disease. Antimetaboilte therapy may allow patients to reduce steroid consumption. Adverse events were more common in patients receiving antimetabolites although differences with placebo were not statistically significant. Azathioprine therapy is inferior to infliximab for induction of steroid-free remission. However, the combination of azathioprine and infliximab was superior to infliximab alone for induction of steroid-free remission.
Topics: Adult; Antimetabolites; Azathioprine; Crohn Disease; Glucocorticoids; Humans; Immunosuppressive Agents; Induction Chemotherapy; Infliximab; Mercaptopurine; Mesalamine; Prednisone; Randomized Controlled Trials as Topic; Sulfasalazine; Withholding Treatment
PubMed: 27783843
DOI: 10.1002/14651858.CD000545.pub5 -
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 -
Journal of the European Academy of... Jul 2019Twenty per cent of patients with plaque psoriasis also have psoriatic arthritis - a disease affecting joints and entheses. Different treatment options exist but... (Meta-Analysis)
Meta-Analysis
Twenty per cent of patients with plaque psoriasis also have psoriatic arthritis - a disease affecting joints and entheses. Different treatment options exist but currently no succinct systematic overview exists. A systematic review of approved systemic treatments for psoriatic arthritis was conducted. We systematically searched in three databases (last update September 2017). Data were extracted for ACR20/50, HAQ-DI, SF-36 and adverse/serious adverse events after 16-24 weeks. We assessed the quality of evidence using GRADE. Twenty trials were included. Three trials compared two active substances. Results for ACR20 were infliximab + methotrexate vs. methotrexate: RR 1.40 (95% CI 1.07-1.84) very low quality evidence; ixekizumab Q2W vs. adalimumab Q2W: RR 1.08 (95% CI 0.86-1.36) very low quality, leflunomide vs. methotrexate: RR 1.01, (95% CI 0.84-1.21) low quality. Eighteen drug vs. placebo comparisons were included. For ACR20/50, HAQ-DI and SF-36, the active treatment was efficacious and the quality of the evidence was mostly moderate to low (15 of 18 comparisons). The quality of evidence for (serious) adverse events was mostly low; differences were rare. In three placebo-controlled comparisons, leflunomide, MTX and sulfasalazine failed to show statistical superiority for ACR. Besides the established treatment of anti-TNF antibodies and ustekinumab for psoriatic arthritis, the newer treatment options of IL17 antibodies and apremilast are also effective for the treatment of psoriatic arthritis. Based on just one comparative trial and one drug each, the new class of anti-IL 17 antibodies appears to be equally effective as the group of anti-TNF antibodies; for apremilast, this is yet unclear.
Topics: Adalimumab; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Arthritis, Psoriatic; Dermatologic Agents; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Infliximab; Leflunomide; Methotrexate; Randomized Controlled Trials as Topic; Sulfasalazine; Thalidomide; Ustekinumab
PubMed: 30735612
DOI: 10.1111/jdv.15482 -
European Review For Medical and... Apr 2021Rheumatoid arthritis is a chronic autoimmune disease. Treatment aims to reduce and improve its signs and symptoms. Hence, Disease-Modifying Antirheumatic Drugs (DMARDs)...
OBJECTIVE
Rheumatoid arthritis is a chronic autoimmune disease. Treatment aims to reduce and improve its signs and symptoms. Hence, Disease-Modifying Antirheumatic Drugs (DMARDs) are the treatment of choice. The objective of this study was to identify potential interactions between DMARDs and the drugs most frequently prescribed in dentistry in order to avoid adverse reactions.
MATERIALS AND METHODS
This literature review sets out to define possible adverse reactions provoked by pharmacological interactions between DMARDs and the drugs commonly prescribed in dentistry. A search was conducted in PubMed by searching the names of drugs used in dentistry, "drug interactions," "rheumatoid arthritis," and "dentistry", "hydroxychloroquine", "leflunomide", "methotrexate", "sulfasalazine", "adalimumab", "anakinra", "etanercept", "abatacept", "infliximab" and "rituximab".
RESULTS
It was found that most DMARDs show potential interactions with many drugs used in dentistry, including various antibiotics, analgesics, anesthetics, antifungals, and corticosteroids.
CONCLUSIONS
It is clinically important for oral health clinicians to be aware of possible drug interactions between DMARDs and the drugs commonly prescribed in dentistry to prevent potential adverse reactions and avoid endangering the patient.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Drug Interactions; Humans
PubMed: 33877648
DOI: 10.26355/eurrev_202104_25536 -
The Cochrane Database of Systematic... Jul 2021Ulcerative colitis (UC) is a chronic inflammation of the colon characterised by periods of relapse and remission. It starts in the rectum and can extend throughout the...
BACKGROUND
Ulcerative colitis (UC) is a chronic inflammation of the colon characterised by periods of relapse and remission. It starts in the rectum and can extend throughout the colon. UC and Crohn's disease (CD) are the most common inflammatory bowel diseases (IBDs). However, UC tends to be more common than CD. It has no known cure but can be managed with medication and surgery. However, studies have shown that abdominal pain persists in up to one-third of people with UC in remission. Abdominal pain could be a symptom of relapse of the disease due to adverse effects of medication, surgical complications and strictures or adhesions secondary to UC.
OBJECTIVES
To assess the efficacy and safety of interventions for managing abdominal pain in people with ulcerative colitis.
SEARCH METHODS
We searched CENTRAL, MEDLINE and five other databases and clinical trials registries on 28 April 2021. We contacted authors of relevant studies and ongoing or unpublished trials that may be relevant to the review. We also searched references of trials and systematic reviews for any additional trials.
SELECTION CRITERIA
All published, unpublished and ongoing randomised trials that compared interventions for the management of abdominal pain with other active interventions or standard therapy, placebo or no therapy were included. People with both active and inactive disease were included. We excluded studies that did not report on any abdominal pain outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted data extraction and 'Risk of bias' assessments. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs), respectively, with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology.
MAIN RESULTS
We included five studies (360 randomised participants). Studies considered mainly participants in an inactive state of the disease. No conclusions could be drawn about the efficacy of any of the interventions on pain frequency, pain intensity, and treatment success. The certainty of the evidence was very low for all comparisons because of imprecision due to sparse data, and risk of bias. One study compared a low FODMAPs diet (n=13) to a sham diet (n=13). The evidence is very uncertain about the effect of this treatment on pain frequency (MD -4.00, 95% CI -20.61 to 12.61) and intensity (MD -9.00, 95% CI -20.07 to 2.07). Treatment success was not reported. One study compared relaxation training (n=20) to wait-list (n=20). The evidence is very uncertain about the effect of this treatment on pain frequency at end of intervention (MD 2.60, 95% CI 1.14 to 4.06) and 6-month follow-up (MD 3.30, 95% CI 1.64 to 4.96). Similarly, the evidence is very uncertain about the effect of this treatment on pain intensity at end of intervention (MD -1.70, 95% CI -2.92 to -0.48) and 6-month follow-up (MD -2.30, 95% CI -3.70 to -0.90). Treatment success was not reported. One study compared yoga (n=30) to no intervention (n=30). The study defined treatment success as the presence or absence of pain; however, the data they provided was unclear. Pain frequency and intensity were not reported. One study compared a kefir diet (Lactobacillus bacteria, n=15) to no intervention (n=15). The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.17, 95% CI -0.91 to 0.57). Pain frequency and treatment success were not reported. One study compared a stellate ganglion block treatment (n=90) to sulfasalazine treatment (n=30). The study defined treatment success as "stomachache"; however, the data they provided was unclear. Pain frequency and intensity were not reported. Two studies reported withdrawals due to adverse events. One study reported withdrawals due to adverse events as zero. Two studies did not report this outcome. We cannot draw any conclusions about the effects of any of the interventions on withdrawals due to adverse events because of the very limited evidence. The reporting of secondary outcomes was inconsistent. Adverse events tended to be very low or zero. However, we can make no clear judgements about adverse events for any of the interventions, due to the low number of events. Anxiety was measured and reported at end of intervention in only one study (yoga versus no intervention), and depression was not measured in any of the studies. We can therefore draw no meaningful conclusions about these outcomes.
AUTHORS' CONCLUSIONS
We found very low-certainty evidence on the efficacy and safety of interventions for the management of abdominal pain in ulcerative colitis. Pervasive issues with very serious imprecision from small samples size and high risk of bias have led to very low-certainty outcomes, precluding conclusions. While few adverse events and no serious adverse events were reported, the certainty of these findings was again very low for all comparisons, so no conclusions can be drawn. There is a need for further research. We have identified eight ongoing studies in this review, so an update will be warranted. It is key that future research addresses the issues leading to reduced certainty of outcomes, specifically sample size and reporting that leads to high risk of bias. It is also important that if researchers are considering pain as a critical outcome, they should report clearly if participants were pain-free at baseline; in that case, data would be best presented as separate subgroups throughout their research.
Topics: Abdominal Pain; Adult; Bias; Colitis, Ulcerative; Diet, Carbohydrate-Restricted; Gastrointestinal Agents; Humans; Kefir; Lactobacillus; Middle Aged; Nerve Block; Randomized Controlled Trials as Topic; Relaxation Therapy; Stellate Ganglion; Sulfasalazine; Waiting Lists; Yoga
PubMed: 34291816
DOI: 10.1002/14651858.CD013589.pub2 -
The Lancet. Gastroenterology &... Nov 2018The majority of patients with ulcerative colitis have mildly to moderately active disease. To inform the management of patients with left-sided or extensive mildly to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The majority of patients with ulcerative colitis have mildly to moderately active disease. To inform the management of patients with left-sided or extensive mildly to moderately active ulcerative colitis, we assessed the comparative efficacy and tolerability of different therapies.
METHODS
In this systematic review and network meta-analysis, we searched Epub, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science from inception to Dec 14, 2015, and updated on MEDLINE on March 1, 2018, for randomised controlled trials in adults (age ≥17 years) with left-sided or extensive mild to moderate ulcerative colitis. Studies were included if patients were treated with oral sulfasalazine, diazo-bonded 5-aminosalicylates (5-ASAs), mesalazine (low dose <2 g/day, standard dose 2-3 g/day, or high dose >3 g/day), controlled ileal-release budesonide, or budesonide multimatrix, alone or in combination with rectal 5-ASA therapy, and were compared with each other or placebo for induction or maintenance of clinical remission. The minimum duration of therapy was 4 weeks for trials of induction and 24 weeks for trials of maintenance therapy. We did pairwise and random-effects network meta-analysis using a frequentist approach, and calculated odds ratios (ORs) and 95% CIs; agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to appraise quality of evidence. We examined heterogeneity with the I statistic.
FINDINGS
Our search identified 1316 unique studies, from which 75 randomised trials with 12 215 patients were eligible for analysis. Based on 48 induction randomised trials (8020 participants) that met inclusion criteria, combined oral and rectal 5-ASAs (SUCRA 0·99) and high-dose mesalazine (>3 g/day; SUCRA 0·82) were ranked highest for induction of remission. Both interventions were superior to standard-dose mesalazine (2-3 g/day; failure to induce remission with combined oral and rectal 5-ASAs OR 0·41, 95% CI 0·22-0·77; high-dose mesalazine 0·78, 0·66-0·93) with moderate confidence in estimates. On the basis of 28 randomised trials (4218 participants) that met inclusion criteria, all interventions were superior to placebo for maintenance of remission; however, neither combined oral and rectal 5-ASAs nor high-dose mesalazine were superior to standard-dose mesalazine.
INTERPRETATION
In patients with mildly to moderately active left-sided or extensive ulcerative colitis, combined oral and topical mesalazine therapy and high-dose mesalazine are superior to standard-dose mesalazine for induction of remission, but not maintenance of remission. Standard-dose mesalazine might be preferred for maintenance in most patients.
FUNDING
None.
Topics: Administration, Oral; Administration, Rectal; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colitis, Ulcerative; Humans; Mesalamine; Network Meta-Analysis; Remission Induction; Sulfasalazine
PubMed: 30122356
DOI: 10.1016/S2468-1253(18)30231-0 -
QJM : Monthly Journal of the... May 2020Acetaminophen (N-acetyl-para-aminophenol, paracetamol, (APAP) toxicity is one of the commonly encountered poisonings by emergency physicians. Methemoglobinemia is an...
BACKGROUND
Acetaminophen (N-acetyl-para-aminophenol, paracetamol, (APAP) toxicity is one of the commonly encountered poisonings by emergency physicians. Methemoglobinemia is an uncommon association and rarely seen in APAP poisoning.
METHODS
Retrospective analysis of all the published reports on APAP induced methemoglobinemia from 1968 to 2019.
RESULTS
In total there were 14 cases with 9 females and 6 males. The median age of the study cohort was 59 years. The most common presenting feature was altered mentation (9 patients) followed by cyanosis (3 patients). The intent of consumption was therapeutic (7 cases) versus suicidal (5 cases) attempt.In most cases, the dose of APAP consumption was not known. Aspirin, sulfasalazine, benzocaine spray, nitrate preservative, contaminated water, detergents, etc. where the other agents consumed by the patients in addition to APAP before developing methemoglobinemia. The median MethHb level of the study cohort was 15.85% Patients were treated with NAC, hemodialysis, methylene blue, and ascorbic acid and CRRT in various combinations. Full recovery was seen in 9 patients while 4 patients died.
CONCLUSION
APAP toxicity is a well-known and common entity with multiple sequelae that presents with a variable spectrum of mild to fulminant multiorgan failure. Awareness of non-classical presentations like methemoglobinemia is essential to ensure timely intervention.
PubMed: 32428237
DOI: 10.1093/qjmed/hcaa174 -
RMD Open 2017Clinical trials have not consistently demonstrated differences between tumour necrosis factor inhibitor (TNFi) plus methotrexate and triple therapy (methotrexate plus...
Systematic review and network meta-analysis of the efficacy and safety of tumour necrosis factor inhibitor-methotrexate combination therapy versus triple therapy in rheumatoid arthritis.
OBJECTIVE
Clinical trials have not consistently demonstrated differences between tumour necrosis factor inhibitor (TNFi) plus methotrexate and triple therapy (methotrexate plus hydroxychloroquine plus sulfasalazine) in rheumatoid arthritis (RA). The study objective was to estimate the efficacy, radiographic benefits, safety and patient-reported outcomes of TNFi-methotrexate versus triple therapy in patients with RA.
METHODS
A systematic review and network meta-analysis (NMA) of randomised controlled trials of TNFi-methotrexate or triple therapy as one of the treatment arms in patients with an inadequate response to or who were naive to methotrexate was conducted. American College of Rheumatology 70% response criteria (ACR70) at 6 months was the prespecified primary endpoint to evaluate depth of response. Data from direct and indirect comparisons between TNFi-methotrexate and triple therapy were pooled and quantitatively analysed using fixed-effects and random-effects Bayesian models.
RESULTS
We analysed 33 studies in patients with inadequate response to methotrexate and 19 in patients naive to methotrexate. In inadequate responders, triple therapy was associated with lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate (OR 0.35, 95% credible interval (CrI) 0.19 to 0.64). Most secondary endpoints tended to favour TNFi-methotrexate in terms of OR direction; however, no clear increased likelihood of achieving these endpoints was observed for either therapy. The odds of infection were lower with triple therapy than with TNFi-methotrexate (OR 0.08, 95% CrI 0.00 to 0.57). There were no differences observed between the two regimens in patients naive to methotrexate.
CONCLUSIONS
In this NMA, triple therapy was associated with 65% lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate in patients with inadequate response to methotrexate. Although secondary endpoints numerically favoured TNFi-methotrexate, no clear differences were observed. The odds of infection were greater with TNFi-methotrexate. No differences were observed for patients naive to methotrexate. These results may help inform care of patients who fail methotrexate first-line therapy.
PubMed: 28123782
DOI: 10.1136/rmdopen-2016-000371 -
The Cochrane Database of Systematic... May 2016Oral 5-aminosalicylic (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral 5-aminosalicylic (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs were more effective than placebo but had a statistically significant therapeutic inferiority relative to SASP. This updated review includes more recent studies and evaluates the effectiveness, dose-responsiveness, and safety of 5-ASA preparations used for maintenance of remission in quiescent ulcerative colitis.
OBJECTIVES
The primary objectives were 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 ulcerative colitis. A secondary objective was 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
A literature search for relevant studies (inception to 9 July 2015) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies.
SELECTION CRITERIA
Studies were accepted for analysis if they were randomized controlled trials with a minimum treatment duration of six months. Studies of oral 5-ASA therapy for treatment of patients with quiescent ulcerative colitis compared with placebo, SASP or other 5-ASA formulations were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose ranging studies were also considered for inclusion.
DATA COLLECTION AND ANALYSIS
The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes included adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA formulation, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol and Salofalk). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis.
MAIN RESULTS
Forty-one studies (8928 patients) were included. The majority of included studies were rated as low risk of bias. Ten studies were rated at high risk of bias. Seven of these studies were single-blind and three studies were open-label. However, two open-label studies and four of the single-blind studies utilized investigator performed endoscopy as an endpoint, which may protect against bias. 5-ASA was significantly superior to placebo for maintenance of clinical or endoscopic remission. Forty-one per cent of 5-ASA patients relapsed compared to 58% of placebo patients (7 studies, 1298 patients; RR 0.69, 95% CI 0.62 to 0.77). There was a trend towards greater efficacy with higher doses of 5-ASA with a statistically significant benefit for the 1 to 1.9 g/day (RR 0.65; 95% CI 0.56 to 0.76) and the > 2 g/day subgroups (RR 0.73, 95% CI 0.60 to 0.89). SASP was significantly superior to 5-ASA for maintenance of remission. Forty-eight per cent of 5-ASA patients relapsed compared to 43% of SASP patients (12 studies, 1655 patients; RR 1.14, 95% CI 1.03 to 1.27). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome for the placebo and SASP-controlled studies was high. No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Twenty-nine per cent of once daily patients relapsed over 12 months compared to 31% of conventionally dosed patients (8 studies, 3127 patients; RR 0.91, 95% CI 0.82 to 1.01). Eleven per cent of patients in the once daily group failed to adhere to their medication regimen compared to 9% of patients in the conventional dosing group (6 studies, 1462 patients; RR 1.22, 95% CI 0.91 to 1.64). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Forty-four per cent of patients in the 5-ASA group relapsed compared to 41% of patients in the 5-ASA comparator group (6 studies, 707 patients; RR 1.08, 95% CI 0.91 to 1.28). A pooled analysis of two studies showed no statistically significant difference in efficacy between Balsalazide 6 g and 3 g/day. Twenty-three per cent of patients in the 6 g/day group relapsed compared to 33% of patients in the 3 g/day group (216 patients; RR 0.76; 95% CI 0.45 to 2.79). One study found Balsalazide 4 g to be superior to 2 g/day. Thirty-seven per cent of patients in the 4 g/day Balsalazide group relapsed compared to 55% of patients in the 2 g/day group (133 patients; RR 0.66; 95% CI 0.45 to 0.97). One study found a statistically significant difference between Salofalk granules 3 g and 1.5 g/day. Twenty-five per cent of patients in the Salofalk 3 g/day group relapsed compared to 39% of patients in the 1.5 g/day group (429 patients; RR 0.65; 95% CI 0.49 to 0.86). Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache, dyspepsia, and nasopharyngitis. There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, 5-ASA and SASP, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulations and 5-ASA dose ranging studies. The trials that compared 5-ASA and SASP may have been biased in favour of SASP because most trials enrolled patients known to be tolerant to SASP which may have minimized SASP-related adverse events.
AUTHORS' CONCLUSIONS
5-ASA was superior to placebo for maintenance therapy in ulcerative colitis. However, 5-ASA had a statistically significant therapeutic inferiority relative to SASP. Oral 5-ASA administered once daily is as effective and safe as conventional dosing for maintenance of remission in quiescent ulcerative colitis. There does not appear to be any difference in efficacy or safety between the various formulations of 5-ASA. Patients with extensive ulcerative colitis or with frequent relapses may benefit from a higher dose of maintenance therapy. High dose therapy appears to be as safe as low dose and is not associated with a higher incidence of adverse events.
Topics: Administration, Oral; Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Humans; Maintenance Chemotherapy; Medication Adherence; Mesalamine; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Sulfasalazine
PubMed: 27158764
DOI: 10.1002/14651858.CD000544.pub4 -
BMC Complementary Medicine and Therapies Oct 2020Ulcerative colitis, characterized by diarrhea, bloody stools and abdominal pain, is a chronic, idiopathic inflammatory disease of the colonic mucosa. In recent years,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ulcerative colitis, characterized by diarrhea, bloody stools and abdominal pain, is a chronic, idiopathic inflammatory disease of the colonic mucosa. In recent years, the incidence of ulcerative colitis presents an increasing trend year by year. Acupuncture, as a potential effective treatment for ulcerative colitis, is widely used in clinical practice.
METHODS
We searched PubMed, the Cochrane Library, Chinese CBM Database, China National Knowledge Infrastructure, Chinese VIP Information, and Wanfang Database from the date of the establishment of each database up to March, 2019. We included randomized controlled clinical trials (RCT) comparing acupuncture versus conventional conventional medicine or comparing acupuncture combined with conventional medicine versus conventional medicine in participants with ulcerative colitis. Two authors screened all references, assessed the risk of bias and extracted data independently. We summarized data using risk ratios (RR) with 95% confidence intervals (CI) for binary outcomes. We performed meta-analyses using random effects model. We assessed overall quality of evidence using GRADE.
RESULTS
We included 13 RCTs (1030 participants, 515 in the acupuncture group and 515 in the control group). Only one study tested head acupuncture, and the other 12 tested body acupuncture. The treatment duration ranged from 14 to 60 days. Seven trials compared acupuncture alone versus conventional medicine, and six compared acupuncture combined with conventional medicine versus conventional medicine. Acupuncture combined with mesalazine showed better clinical effect (improved clinical symptoms, colonoscopy results and stool examination results) (RR 1.25, 95% CI 1.19 to 1.41; 232 participants; 4 trials; low quality evidence) and better colonoscopy curative effect (RR 1.33, 95% CI 1.04 to 1.71; 108 participants; 2 trials; moderate quality evidence) compared to mesalazine. Acupuncture showed better clinical effect compared to the combination of metronidazole and sulfasalazine (RR 1.21, 95%CI 1.10, 1.34; 318 participants; 3 trials; moderate quality evidence). There was no significant difference in the incidence of adverse events between groups.
CONCLUSIONS
Both acupuncture alone and acupuncture combined with conventional medicine may be effective in treating ulcerative colitis compared to conventional medicine. Our findings must be interpreted with caution due to high or unclear risk of bias of the included trials.
Topics: Acupuncture Therapy; Colitis, Ulcerative; Combined Modality Therapy; Humans; Randomized Controlled Trials as Topic
PubMed: 33054760
DOI: 10.1186/s12906-020-03101-4