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The Cochrane Database of Systematic... Feb 2019Several antibiotics have been evaluated in Crohn's disease (CD), however randomised controlled trials (RCTs) have produced conflicting results. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several antibiotics have been evaluated in Crohn's disease (CD), however randomised controlled trials (RCTs) have produced conflicting results.
OBJECTIVES
To assess the efficacy and safety of antibiotics for induction and maintenance of remission in CD.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register and Clinicaltrials.gov database from inception to 28 February 2018. We also searched reference lists and conference proceedings.
SELECTION CRITERIA
RCTs comparing antibiotics to placebo or an active comparator in adult (> 15 years) CD patients were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors screened search results and extracted data. Bias was evaluated using the Cochrane risk of bias tool. The primary outcomes were failure to achieve clinical remission and relapse. Secondary outcomes included clinical response, endoscopic response, endoscopic remission, endoscopic relapse, histologic response, histologic remission, adverse events (AEs), serious AEs, withdrawal due to AEs and quality of life. Remission is commonly defined as a Crohn's disease activity index (CDAI) of < 150. Clinical response is commonly defined as a decrease in CDAI from baseline of 70 or 100 points. Relapse is defined as a CDAI > 150. For studies that enrolled participants with fistulizing CD, response was defined as a 50% reduction in draining fistulas. Remission was defined as complete closure of fistulas. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes. We calculated the mean difference (MD) and corresponding 95% CI for continuous outcomes. GRADE was used to assess the certainty of the evidence.
MAIN RESULTS
Thirteen RCTs (N = 1303 participants) were eligible. Two trials were rated as high risk of bias (no blinding). Seven trials were rated as unclear risk of bias and four trials were rated as low risk of bias. Comparisons included ciprofloxacin (500 mg twice daily) versus placebo, rifaximin (800 to 2400 mg daily) versus placebo, metronidazole (400 mg to 500 mg twice daily) versus placebo, clarithromycin (1 g/day) versus placebo, cotrimoxazole (960 mg twice daily) versus placebo, ciprofloxacin (500 mg twice daily) and metronidazole (250 mg four time daily) versus methylprednisolone (0.7 to 1 mg/kg daily), ciprofloxacin (500 mg daily), metronidazole (500 mg daily) and budesonide (9 mg daily) versus placebo with budesonide (9 mg daily), ciprofloxacin (500 mg twice daily) versus mesalazine (2 g twice daily), ciprofloxacin (500 mg twice daily) with adalimumab versus placebo with adalimumab, ciprofloxacin (500 mg twice daily) with infliximab versus placebo with infliximab, clarithromycin (750 mg daily) and antimycobacterial versus placebo, and metronidazole (400 mg twice daily) and cotrimoxazole (960 mg twice daily) versus placebo. We pooled all antibiotics as a class versus placebo and antibiotics with anti-tumour necrosis factor (anti-TNF) versus placebo with anti-TNF.The effect of individual antibiotics on CD was generally uncertain due to imprecision. When we pooled antibiotics as a class, 55% (289/524) of antibiotic participants failed to achieve remission at 6 to 10 weeks compared with 64% (149/231) of placebo participants (RR 0.86, 95% CI 0.76 to 0.98; 7 studies; high certainty evidence). At 10 to 14 weeks, 41% (174/428) of antibiotic participants failed to achieve a clinical response compared to 49% (93/189) of placebo participants (RR 0.77, 95% CI 0.64 to 0.93; 5 studies; moderate certainty evidence). The effect of antibiotics on relapse in uncertain. Forty-five per cent (37/83) of antibiotic participants relapsed at 52 weeks compared to 57% (41/72) of placebo participants (RR 0.87, 95% CI 0.52 to 1.47; 2 studies; low certainty evidence). Relapse of endoscopic remission was not reported in the included studies. Antibiotics do not appear to increase the risk of AEs. Thirty-eight per cent (214/568) of antibiotic participants had at least one adverse event compared to 45% (128/284) of placebo participants (RR 0.87, 95% CI 0.75 to 1.02; 9 studies; high certainty evidence). The effect of antibiotics on serious AEs and withdrawal due to AEs was uncertain. Two per cent (6/377) of antibiotic participants had at least one adverse event compared to 0.7% (1/143) of placebo participants (RR 1.70, 95% CI 0.29 to 10.01; 3 studies; low certainty evidence). Nine per cent (53/569) of antibiotic participants withdrew due to AEs compared to 12% (36/289) of placebo participants (RR 0.86, 95% CI 0.57 to 1.29; 9 studies; low certainty evidence) is uncertain. Common adverse events in the studies included gastrointestinal upset, upper respiratory tract infection, abscess formation and headache, change in taste and paraesthesiaWhen we pooled antibiotics used with anti-TNF, 21% (10/48) of patients on combination therapy failed to achieve a clinical response(50% closure of fistulas) or remission (closure of fistulas) at week 12 compared with 36% (19/52) of placebo and anti-TNF participants (RR 0.57, 95% CI 0.29 to 1.10; 2 studies; low certainty evidence). These studies did not assess the effect of antibiotics and anti-TNF on clinical or endoscopic relapse. Seventy-seven per cent (37/48) of antibiotics and anti-TNF participants had an AE compared to 83% (43/52) of anti-TNF and placebo participants (RR 0.93, 95% CI 0.76 to 1.12; 2 studies, moderate certainty evidence). The effect of antibiotics and anti-TNF on withdrawal due to AEs is uncertain. Six per cent (3/48) of antibiotics and anti-TNF participants withdrew due to an AE compared to 8% (4/52) of anti-TNF and placebo participants (RR 0.82, 95% CI 0.19 to 3.45; 2 studies, low certainty evidence). Common adverse events included nausea, vomiting, upper respiratory tract infections, change in taste, fatigue and headache AUTHORS' CONCLUSIONS: Moderate to high quality evidence suggests that any benefit provided by antibiotics in active CD is likely to be modest and may not be clinically meaningful. High quality evidence suggests that there is no increased risk of adverse events with antibiotics compared to placebo. The effect of antibiotics on the risk of serious adverse events is uncertain. The effect of antibiotics on maintenance of remission in CD is uncertain. Thus, no firm conclusions regarding the efficacy and safety of antibiotics for maintenance of remission in CD can be drawn. More research is needed to determine the efficacy and safety of antibiotics as therapy in CD.
Topics: Anti-Bacterial Agents; Crohn Disease; Humans; Induction Chemotherapy; Maintenance Chemotherapy; Randomized Controlled Trials as Topic
PubMed: 30731030
DOI: 10.1002/14651858.CD012730.pub2 -
Nutrients Jan 2019Studies of probiotics, fructan-type prebiotics, and synbiotics in patients with ulcerative colitis (UC) show significant heterogeneity in methodology and results. Here,... (Meta-Analysis)
Meta-Analysis
Studies of probiotics, fructan-type prebiotics, and synbiotics in patients with ulcerative colitis (UC) show significant heterogeneity in methodology and results. Here, we study the efficacy of such interventions and the reasons for the heterogeneity of their results. Eligible random controlled trials were collected from the PUBMED and SCOPUS databases. A total of 18 placebo-controlled and active treatment-controlled (i.e., mesalazine) studies were selected with a Jadad score ≥ 3, including 1491 patients with UC. Data for prebiotics and synbiotics were sparse and consequently these studies were excluded from the meta-analysis. The UC remission efficacy of probiotics was measured in terms of relative risk (RR) and odds ratio (OR). Significant effects were observed in patients with active UC whenever probiotics containing bifidobacteria were used, or when adopting the US Food and Drug Administration (FDA)-recommended scales (UC Disease Activity Index and Disease Activity Index). By the FDA recommended scales, the RR was 1.55 (CI95%: 1.13⁻2.15, -value = 0.007, ² = 29%); for bifidobacteria-containing probiotics, the RR was 1.73 (CI95%: 1.23⁻2.43, -value = 0.002, ² = 35%). No significant effects were observed on the maintenance of remission for placebo-controlled or mesalazine-controlled studies. We conclude that a validated scale is necessary to determine the state of patients with UC. However, probiotics containing bifidobacteria are promising for the treatment of active UC.
Topics: Colitis, Ulcerative; Fructans; Humans; Prebiotics; Probiotics; Remission Induction; Synbiotics
PubMed: 30704039
DOI: 10.3390/nu11020293 -
World Journal of Clinical Cases Dec 2018To assess the effects of probiotic Medilac-S as adjunctive therapy for the induction of remission of ulcerative colitis (UC) in a Chinese population through a systematic...
AIM
To assess the effects of probiotic Medilac-S as adjunctive therapy for the induction of remission of ulcerative colitis (UC) in a Chinese population through a systematic review and meta-analysis.
METHODS
A systematic literature search was conducted to find randomized, controlled trials in a Chinese population with at least two study arms - a control arm which receives a conventional, oral aminosalicylate drug, and a treatment arm, which administers the same conventional drug in conjunction with the probiotic Medilac-S . Both English and Chinese databases were searched, including PubMed, EMBASE, Google Scholar, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Search, and study data was extracted onto standardized abstraction sheets. Meta-analyses were conducted for primary and secondary outcomes of interest using a fixed or random effects model. The primary outcome was the induction of clinical remission and the secondary outcomes included changes in Sutherland index, endoscopic and histological scores, proportion of reported clinical symptoms and adverse events (AEs). For outcomes with sufficient data, the type of conventional drug therapy was also assessed to determine if the effects of combination therapy with Medilac-S was influenced by drug type. All tests were conducted using a type I error rate of 0.05 and all confidence intervals (CI) were based on a 95% confidence level. Review protocol was uploaded to PROSPERO (CRD42018085658 upon completion).
RESULTS
Fifty-three clinical trials with a total of 3984 participants were identified and included in the review. Medilac-S adjunctive therapy significantly improved induction of clinical remission (RR = 1.21; 95%CI: 1.18-1.24; < 0.0001) with the estimated likelihood of effective treatment, on average, 21% higher for those consuming the probiotic. Sutherland index scores showed the control mean was on average 3.10 (CI: 2.41-3.78; = 0.0428) units greater than the treatment mean, thereby demonstrating significant improvement in participants taking the probiotic. Similarly, a significant difference was seen between the overall reduction of endoscopic and histological scores of control and treatment arm participants, with score decreases in the control groups 0.71 (CI: 0.3537-1.0742) and 1.1 (CI: 0.9189-1.2300) units smaller than treatment group score decreases. The proportion of participants reporting clinical symptoms, (abdominal pain, tenesmus, blood and mucous in stool, and diarrhea) was significantly reduced after combination therapy with Medilac-S ( < 0.0001) and estimated to be on average 44% (RR = 0.44, CI: 0.32-0.59), 53% (RR = 0.53, CI: 0.38-74), 40% (RR = 0.40, CI: 0.28-0.58) and 47% (RR = 0.47 CI: 0.36-0.42) respectively, of the proportion of individuals reporting the aforementioned symptoms after conventional therapy alone. The risk of AEs was also significantly reduced with adjunctive Medilac-S therapy. The proportion of individuals in the treatment groups reporting AEs was an estimated 72% of the proportion of individuals in the control groups reporting AEs (RR = 0.72, CI: 0.55-0.94, = 0.0175). Upon comparing effect means for different drug types in conjunction with Medilac-S, evidence of significant variability ( < 0.0001) was observed, and sulfasalazine was found to be the most effective drug in both primary and secondary outcomes.
CONCLUSION
Evidence suggests Medilac-S adjunctive therapy should be considered standard care for UC in a Chinese population because it aids in the induction of clinical remission, improves symptoms of the gastrointestinal tract and reduces risk of AEs.
PubMed: 30568952
DOI: 10.12998/wjcc.v6.i15.961 -
Journal of Crohn's & Colitis May 2019Surgery is an important treatment for Crohn's disease [CD], but recurrence occurs in up to 80% of individuals post-operatively. The efficacy of several drugs to prevent... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Surgery is an important treatment for Crohn's disease [CD], but recurrence occurs in up to 80% of individuals post-operatively. The efficacy of several drugs to prevent post-operative recurrence has been studied in previous meta-analyses, but a number of randomized controlled trials [RCTs] have recently been published. We therefore performed an updated systematic review and network meta-analysis to investigate this issue.
METHODS
We performed a comprehensive literature search through to July 2018 to identify RCTs investigating the endoscopic and clinical recurrence of CD at 12 months post-operatively. We performed a random-effects network meta-analysis to produce a pooled relative risk [RR] with 95% confidence intervals [CIs]. We ranked the treatments according to their P-score.
RESULTS
We included 10 RCTs, containing 751 patients, in our primary analysis of endoscopic recurrence of CD at 12 months. Anti-tumour necrosis factor [TNF]-α therapies were significantly better than placebo, either alone [P-score 0.98, RR 0.13; 95% CI 0.04-0.39] or in combination with 5-aminosalicylates [5-ASAs] [P-score 0.81, RR 0.30; 95% CI 0.12-0.75], or 5-nitroimidazoles [P-score 0.75, RR 0.40; 95% CI 0.23-0.69]. Combination therapy with a thiopurine and 5-nitroimidazole was also more effective than placebo [P-score 0.59, RR 0.56; 95% CI 0.40-0.80], as was thiopurine monotherapy [P-score 0.31, RR 0.84; 95% CI 0.74-0.94]. However, neither 5-nitroimidazoles nor 5-ASAs alone were superior to placebo.
CONCLUSIONS
In network meta-analysis, anti-TNF-α therapies alone, or in combination, appear to be the best medications for preventing endoscopic post-operative recurrence of CD.
Topics: Anti-Inflammatory Agents; Crohn Disease; Humans; Mesalamine; Nitroimidazoles; Secondary Prevention; Tumor Necrosis Factor-alpha
PubMed: 30561586
DOI: 10.1093/ecco-jcc/jjy216 -
The American Journal of the Medical... Oct 2018Ulcerative Colitis (UC) is characterized by chronic inflammation of the mucosal layers of the colon. Treatment of refractory UC is challenging and has a huge healthcare... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ulcerative Colitis (UC) is characterized by chronic inflammation of the mucosal layers of the colon. Treatment of refractory UC is challenging and has a huge healthcare burden. Although there have been advancements in immunomodulatory therapies, these require a step-up financially, and these medications are also associated with significant adverse events. Curcumin, an active ingredient of turmeric, has been studied in the past and found to be useful in the treatment of UC when used as an adjuvant along with mesalamine. We did a systematic review and meta-analysis to explore the role curcumin plays in clinical and endoscopic remission in patients with UC.
MATERIALS AND METHODS
A comprehensive literature review was conducted by first searching the MEDLINE, Pubmed, and Embase databases through December 2017 to identify all studies that compared the use of curcumin when used along with mesalamine with placebo for clinical and endoscopic improvement and remission.
RESULTS
Three randomized controlled trials including 142 patients were included in the study. Use of curcumin along with mesalamine was associated with increased odds of clinical remission (pooled odds ratio of 6.78, 95% CI: 2.39-19.23, P = 0.042). Clinical improvement, endoscopic remission and improvement rate also trended higher in the curcumin group compared to placebo.
CONCLUSIONS
This study demonstrates higher clinical remission rates when curcumin was used in combination with mesalamine to achieve remission in patients with UC. Curcumin, due to its cost effectiveness and safer side effect profile, can decrease the healthcare burden and morbidity associated with this relapsing and remitting disease.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Endoscopy; Humans; Mesalamine; Remission Induction
PubMed: 30360803
DOI: 10.1016/j.amjms.2018.06.023 -
Canadian Journal of Gastroenterology &... 2018Diverticular disease treatment is limited to fibres, antibiotics, and surgery. There is conflicting evidence on mesalazine benefits and harms.
BACKGROUND
Diverticular disease treatment is limited to fibres, antibiotics, and surgery. There is conflicting evidence on mesalazine benefits and harms.
AIM
We systematically reviewed current evidence on benefits and harms of mesalazine versus all other treatments in people with diverticular disease.
METHODS
We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov for studies published to July 2018. We estimated risk ratios (RR) for dichotomous outcomes (disease remission/recurrence, acute diverticulitis in symptomatic uncomplicated diverticular disease, need for surgery/hospitalization, all-cause/disease-related mortality, adverse events), mean differences (MD) or standardized MD (SMD) for continuous outcomes (quality of life, symptoms score, time to recurrence/remission), and their 95% confidence intervals (CI) using random-effects models. We quantified heterogeneity by Chi and I tests. We performed subgroup analyses by disease subtype, comparator, follow-up duration, mesalazine dose, and mode of administration.
RESULTS
We identified 13 randomized trials (n=3028 participants). There was a higher likelihood of disease remission with mesalazine than controls in acute uncomplicated diverticulitis (1 trial, 81 participants, RR=2.67, 95%CI=1.05-6.79), but not in symptomatic uncomplicated diverticular disease (1 trial, 123 participants, RR=1.04, 95%CI=0.81-1.34). There was a lower likelihood of disease recurrence with mesalazine than controls in symptomatic uncomplicated diverticular disease (2 trials, 216 participants, RR=0.52, 95%CI=0.28-0.97), but not in acute uncomplicated diverticulitis (7 trials, 2196 participants, RR=0.90, 95%CI=0.61-1.33). There was no difference in the likelihood of developing acute diverticulitis in symptomatic uncomplicated diverticular disease between the two groups (3 trials, 484 participants, RR=0.26, 95%CI=0.06-1.20). There was a higher global symptoms score reduction with mesalazine than controls in symptomatic uncomplicated diverticular disease (2 trials, 326 participants, SMD=-1.01, 95%CI=-1.51,-0.52) and acute uncomplicated diverticulitis (2 trials, 153 participants, SMD=-0.56, 95%CI=-0.88,-0.24).
CONCLUSIONS
Mesalazine may reduce recurrences in symptomatic uncomplicated diverticular disease. There is uncertainty on the effect of mesalazine in achieving diverticular disease remission. Mesalazine may not prevent acute diverticulitis in symptomatic uncomplicated diverticular disease.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diverticular Diseases; Diverticulitis; Diverticulum, Colon; Female; Humans; Male; Mesalamine; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome
PubMed: 30320044
DOI: 10.1155/2018/5437135 -
Journal of Gastrointestinal and Liver... Sep 2018Symptomatic Uncomplicated Diverticular disease (SUDD) affects about 25% of patients harboring colonic diverticula. We assessed the effectiveness of mesalazine in... (Meta-Analysis)
Meta-Analysis
Mesalazine to treat symptomatic uncomplicated diverticular disease and to prevent acute diverticulitis occurrence. A systematic review with meta-analysis of randomized, placebo-controlled trials.
BACKGROUND AND AIMS
Symptomatic Uncomplicated Diverticular disease (SUDD) affects about 25% of patients harboring colonic diverticula. We assessed the effectiveness of mesalazine in improving symptoms (namely abdominal pain, primary outcome) and in preventing diverticulitis occurrence (secondary outcome) in patients with SUDD.
METHODS
Pertinent studies were selected from the Medline and the Cochrane Central Register of Controlled Trials. Only randomized clinical trials (RCTs) (irrespective of language, blinding, or publication status), which compared mesalazine, irrespective of the dosage assumption, with placebo in SUDD were evaluated.
RESULTS
Four RCTs enrolled 379 patients, 197 treated with mesalazine and 182 with placebo. Two studies provided data on symptom relief according to definition: it was achieved in 97/121 (80%) patients in the mesalazine group and in 81/129 (62.7%) patients in the placebo group (OR 0.43; 95% CI 0.24-0.75; p=0.003 in favour of the mesalazine group). Two studies provided information regarding occurrence of diverticulitis during follow-up. It occurred in 23/119 (19.3%) patients in the mesalazine group and in 34/102 (33.3%) patients in the placebo group (OR 0.35; 95% CI 0.17-0.70; p=0.003 in favour of the mesalazine group).
CONCLUSIONS
Treatment with mesalazine seems to be effective in achieving symptom relief and in the primary prevention of diverticulitis in patients with SUDD.
Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Diverticulitis, Colonic; Diverticulum, Colon; Female; Gastrointestinal Agents; Humans; Male; Mesalamine; Middle Aged; Primary Prevention; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome; Young Adult
PubMed: 30240473
DOI: 10.15403/jgld.2014.1121.273.pic -
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 -
The Cochrane Database of Systematic... Aug 2018Prevention of relapse is a major issue in the management of quiescent Crohn's disease (CD). Current therapies (e.g. methotrexate, biologics, 6-mercaptopurine and...
BACKGROUND
Prevention of relapse is a major issue in the management of quiescent Crohn's disease (CD). Current therapies (e.g. methotrexate, biologics, 6-mercaptopurine and azathioprine) may be effective for maintaining remission in CD, but these drugs may cause significant adverse events. Interventions that are effective and safe for maintenance of remission in CD are desirable.
OBJECTIVES
The primary objectives were to evaluate the efficacy and safety of enteral nutrition for the maintenance of remission in CD and to assess the impact of formula composition on effectiveness.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register and clinicaltrials.gov from inception to 27 July 2018. We also searched references of retrieved studies and reviews.
SELECTION CRITERIA
Randomised controlled trials (RCTs) including participants of any age with quiescent CD were considered for inclusion. Studies that compared enteral nutrition with no intervention, placebo or any other intervention were selected for review.
DATA COLLECTION AND ANALYSIS
Two authors independently screened studies for inclusion, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was clinical or endoscopic relapse as defined by the primary studies. Secondary outcomes included anthropometric measures (i.e. height and weight), quality of life (QoL), adverse events, serious adverse events and withdrawal due to adverse events. We calculated the risk ratio and 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference and 95% CI. A random-effects model was used for the statistical analysis. We used the GRADE criteria to assess the overall certainty of the evidence supporting the primary outcome and selected secondary outcomes.
MAIN RESULTS
Four RCTs (262 adult participants) met the inclusion criteria. One study (N = 33) compared an elemental diet to a non-elemental (polymeric) diet. One study (N = 51) compared a half elemental diet to a regular free diet. Another study (N = 95) compared an elemental diet to 6-mercaptopurine (6-MP) or a no treatment control group. One study (N= 83) compared a polymeric diet to mesalamine. Two studies were rated as high risk of bias due to lack of blinding or incomplete outcome data. The other two studies were judged to have an unclear risk of bias. The studies were not pooled due to differences in control interventions and the way outcomes were assessed.The effect of an elemental diet compared to a polymeric diet on remission rates or withdrawal due to adverse events is uncertain. Fifty-eight per cent (11/19) of participants in the elemental diet group relapsed at 12 months compared to 57% (8/14) of participants in the polymeric diet group (RR 1.01, 95% CI 0.56 to 1.84; very low certainty evidence). Thirty-two per cent (6/19) of participants in the elemental diet group were intolerant to the enteral nutritional formula because of taste or smell and were withdrawn from the study in the first 2 weeks compared to zero participants (0/14) in the polymeric diet group (RR 9.75, 95% CI 0.59 to 159.93; low certainty evidence). Anthropometric measures, QoL, adverse events and serious adverse events were not reported as outcomes.The effect of an elemental diet (half of total daily calorie requirements) compared to a normal free diet on relapse rates is uncertain. Thirty-five per cent (9/26) of participants in the elemental diet group relapsed at 12 months compared to 64% (16/25) of participants in the free diet group (RR 0.54, 95% CI 0.30 to 0.99; very low certainty evidence). No adverse events were reported. This study reported no differences in weight change between the two diet groups. Height and QoL were not reported as outcomes.The effect of an elemental diet compared to 6-MP on relapse rates or adverse events is uncertain. Thirty-eight per cent (12/32) of participants in the elemental diet group relapsed at 12 months compared to 23% (7/30) of participants in the 6-MP group (RR 1.61; 95% CI 0.73 to 3.53; very low certainty evidence). Three per cent (1/32) of participants in the elemental diet group had an adverse event compared to 13% (4/30) of participants in the 6-MP group (RR 0.23, 95% CI 0.03 to 1.98; low certainty evidence). Adverse events in the elemental diet group included surgery due to worsening CD. Adverse events in the 6-MP group included liver injury (n = 2), hair loss (n = 1) and surgery due to an abscess (n = 1). No serious adverse events or withdrawals due to adverse events were reported. Weight, height and QoL were not reported as outcomesThe effect of a polymeric diet compared to mesalamine on relapse rates and weight is uncertain. Forty-two per cent (18/43) of participants in the polymeric diet group relapsed at 6 months compared to 55% (22/40) of participants in the mesalamine group (RR 0.76; 95% CI 0.49 to 1.19; low certainty evidence). The mean difference in weight gain over the study period was 1.9 kg higher in the polymeric diet group compared to mesalamine (95% CI -4.62 to 8.42; low certainty evidence). Two participants in the polymeric diet group experienced nausea and four had diarrhoea. It is unclear if any participants in the mesalamine group had an adverse event. Height, QoL, serious adverse events and withdrawal due to adverse events were not reported as outcomes.
AUTHORS' CONCLUSIONS
The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn. More research is needed to determine the efficacy and safety of using enteral nutrition as maintenance therapy in CD. Currently, there are four ongoing studies (estimated enrolment of 280 participants). This review will be updated when the results of these studies are available.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites; Crohn Disease; Diet; Enteral Nutrition; Food, Formulated; Humans; Maintenance Chemotherapy; Mercaptopurine; Mesalamine; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 30098021
DOI: 10.1002/14651858.CD005984.pub3 -
Value in Health Regional Issues Dec 2018Inflammatory bowel disease (IBD) is the name given to two inflammatory diseases of the colon and/or small intestine: Crohn disease (CD) and ulcerative colitis (UC)....
BACKGROUND
Inflammatory bowel disease (IBD) is the name given to two inflammatory diseases of the colon and/or small intestine: Crohn disease (CD) and ulcerative colitis (UC). There is no information summarizing the complete body of evidence about IBD in developing regions, including Latin America.
OBJECTIVES
To estimate the burden of IBD in Latin America.
METHODS
We conducted a systematic review searching published and unpublished studies on major international and regional databases from January 2000 to September 2015. Outcomes considered were incidence, prevalence, mortality, hospitalization attributable, treatment patterns, comparative effectiveness, patient-reported outcomes, and adherence to treatment. Pairs of reviewers independently selected, extracted, and assessed the risk of bias of the studies. Discrepancies were solved by consensus.
RESULTS
We retrieved 3445 references, finally including 25 studies. Only 19% of the observational studies had a low risk of bias for participant selection and 60% were based on registries. The incidence ranged from 0.74 to 6.76/100,000 person-years for UC and from 0.24 to 3.5/100,000 person-years for CD. The prevalence rate ranged from 0.99 to 44.3/100,000 inhabitants for UC and 0.24 to 16.7/100,000 inhabitants for CD. Mortality rates ranged from 0.60 to 1.02 for UC and from 0.23 to 0.40 for CD. Patient-reported outcomes showed a decrease in quality of life associated with depression and anxiety and correlated with the time of diagnosis. The most frequently used medication in the studies was mesalazine.
CONCLUSIONS
The burden of IBD in Latin America seems to be important, but there is a considerable gap of high-quality evidence in the region.
Topics: Cost of Illness; Developing Countries; Humans; Incidence; Inflammatory Bowel Diseases; Latin America; Mesalamine; Quality of Life
PubMed: 29936359
DOI: 10.1016/j.vhri.2018.03.010