Maintenance Of Remission In Crohn's Disease Research Articles

Linking Strain Engraftment in Fecal Microbiota Transplantation With Maintenance of Remission in Crohn’s Disease

Crohn's disease (CD) is a chronic gastrointestinal disease resulting from the dysfunctional interplay between genetic susceptibility, the immune system, and commensal intestinal microbiota. Emerging evidence suggests that treatment by suppression of the immune response and replacement of the microbiota through fecal microbiota transplantation (FMT) is a promising approach for the treatment of CD. We obtained stool metagenomes from CD patients in remission and assessed gut microbiome composition before and after FMT at the species and strain levels. Longitudinal follow-up evaluation allowed us to identify the gain, loss, and strain replacement of specific species and link these events to the maintenance of remission in CD. We found that FMT had a significant long-term effect on patient microbial compositions, although this was primarily driven by the engraftment of donor species, which remained at low abundance. Thirty-eight percent of FMT-driven changes were strain replacements, emphasizing the importance of detailed profiling methods, such as metagenomics. Several instances of long-term coexistence between donor and patient strains were also observed. Engraftment of some Actinobacteria, and engraftment or loss of Proteobacteria, were related to better disease outcomes in CD patients who received FMT, and transmission of Bacteroidetes was deleterious. Our results suggest clades that may be beneficial to transmit/eliminate through FMT, and provide criteria that may help identify personalized FMT donors to more effectively maintain remission in CD patients. The framework established here creates a foundation for future studies centered around the application of FMT and defined microbial communities as a therapeutic approach for treating CD.

Antibiotics for induction and maintenance of remission in Crohn's disease.

Antibiotics for induction and maintenance of remission in Crohn's disease.

Enteral nutrition for maintenance of remission in Crohn's disease.

Enteral nutrition for maintenance of remission in Crohn's disease.

Antibiotics for induction and maintenance of remission in Crohn's disease

Antibiotics for induction and maintenance of remission in Crohn's disease

European experience with methotrexate treatment in Crohn's disease: a multicenter retrospective analysis.

Methotrexate (MTX) has been utilized for the treatment of Crohn's disease (CD) for decades. Nevertheless, current data provide equivocal evidence on the efficacy of MTX in CD.The aims of this study were to describe the efficacy of MTX for maintenance of remission in CD and to identify the factors associated with the probability of steroid-free clinical remission in a multicenter European referral center cohort. This was a retrospective cohort analysis. Consecutive patients treated with MTX for CD were included from 11 referral centers. Patients receiving concomitant treatment with tumor necrosis factor inhibitors or thiopurines were excluded. The main outcome was steroid-free clinical remission; the secondary outcomes included the rate of complications leading to MTX discontinuation and duration of relapse-free survival in patients achieving the main outcome. Between July 1992 and January 2012, 118 patients were identified for inclusion. MTX administration route was oral for induction in 31.4% and for maintenance in 49.1% of the patients. Steroid-free remission was achieved in 44/118 (37.2%) patients and was maintained relapse free by 28/44 (63.6%) for a median of 12 (3.5-18.5) months. At least one adverse effect was reported by 28.9% of the patients. No clinical or demographic factors were associated with either likelihood of achieving a clinical response or duration of relapse-free survival. MTX treatment induced steroid-free clinical remission in over a third of CD patients and maintained it for a year in almost two-thirds of the responders. MTX should be considered a viable therapeutic option in CD patients refractory to other therapies.

Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease.

The anti-inflammatory effects of n-3 (omega-3 fatty acids, fish oil) have been suggested to be beneficial in chronic inflammatory disorders such as inflammatory bowel disease. This review is an update of a previously published Cochrane review. To systematically review the efficacy and safety of n-3 for maintenance of remission in Crohn's disease (CD). The following databases were searched from inception to November 2013 without language restriction: CENTRAL, MEDLINE, EMBASE, HealthSTAR, PubMed, and ACP journal club. Randomized placebo-controlled trials (RCT) of n-3 for maintenance of remission in CD were included. Studies must have enrolled patients of any age group, who were in remission at the time of recruitment, and were followed for at least six months. The intervention must have been fish oil or n-3 given in pre-defined dosage. Co-interventions were allowed only if they were balanced between the study groups. The primary outcome was the relapse rate and secondary outcomes included change in disease activity scores, time to first relapse and adverse events. Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary and selected secondary outcomes was reassessed for the current update using the GRADE system. We used the RevMan software for analyses. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes and the hazard ratio and 95% CI for time-to-event outcomes. Random-effects or fixed-effect models were used according to degree of heterogeneity and sensitivity analyses were performed in an attempt to explore possible sources of heterogeneity. Six studies with a total of 1039 patients were eligible for inclusion. The two largest studies were rated as low risk of bias for all assessed items. Four studies were rated as unclear risk of bias for randomization and allocation concealment. Two studies were rated as high risk of bias for incomplete outcome data and selective reporting. There was a marginal significant benefit of n-3 therapy for maintenance of remission. Thirty-nine per cent of patients in the n-3 group relapsed at 12 months compared to 47% of placebo patients (6 studies, 1039 patients; RR 0.77, 95% CI 0.61 to 0.98). A GRADE analysis rated the overall quality of the evidence for the primary outcome (i.e. relapse) as very low due to unexplained heterogeneity (I2 = 58%), publication bias, and a high or unknown risk of bias in four studies in the pooled analysis. When two large studies at low risk of bias were considered the benefit was no longer statistically significant. Thirty-seven per cent of patients in the n-3 group relapsed at 12 months compared to 42% of placebo patients (2 studies, 738 patients; RR 0.88, 95% CI 0.74 to 1.05). No significant heterogeneity was identified for this pooled analysis ( I2 = 0%). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (294 events). No serious adverse events were recorded in any of the studies but in a pooled analyses there was a significantly higher rate of diarrhea (4 studies, 862 patients; RR 1.36 95% CI 1.01 to 1.84) and upper gastrointestinal tract symptoms (5 studies, 999 patients; RR 1.65, 95% CI 1.25 to 2.18) in the n-3 treatment group. Evidence from two large high quality studies suggests that omega 3 fatty acids are probably ineffective for maintenance of remission in CD. Omega 3 fatty acids appear to be safe although they may cause diarrhea and upper gastrointestinal tract symptoms.

Probiotic treatments for induction and maintenance of remission in inflammatory bowel diseases: a meta-analysis of randomized controlled trials.

Probiotics have been used for the treatment of inflammatory bowel diseases (IBD). However, the effects of probiotics on the induction and maintenance of remission in ulcerative colitis (UC) or Crohn's disease (CD) still remain controversial. This systematic review verified the findings of high-quality randomized controlled trials (RCTs) which investigated the therapeutic effects of probiotics on IBD. After the quality assessment, 20 RCTs which investigated the effects of probiotics on the induction or maintenance of remission in IBD were identified. From the results of the validation of these RCTs, beneficial effects of probiotic treatments to improve the response rate and remission rate on the remission induction therapies [risk ratio (RR) 1.81; 95 % confidence interval (CI) 1.40-2.35 and RR 1.56; 95 % CI 0.95-2.56, respectively] were verified. Furthermore, probiotic treatments exhibited effects equal to mesalazine on the maintenance of remission in UC (RR 1.00; 95 % CI 0.79-1.26). In contrast, no significant effect of probiotic treatments was shown in either the induction or maintenance of remission in CD. Because there were many variations in the conditions among these studies, a further analysis evaluating the effects of probiotic treatments in IBD is needed to clarify the optimal probiotics and treatment regimens for each condition or population in IBD patients.

Budesonide for Maintenance of Remission in Crohnʼs Disease: Update of a Systematic Review and Meta-analysis for the Cochrane Collaboration

Purpose: Budesonide (BUD) has been shown to be effective for induction of remission in Crohn's disease (CD), but concerns have been raised about the efficacy and safety of its long-term use. This systematic review and meta-analysis examined the efficacy and safety of BUD for maintenance of remission in CD. Methods: MEDLINE, EMBASE, other electronic databases, article reference lists, and conference proceedings were searched up to January, 2013 to identify randomized controlled trials on BUD. Those comparing BUD to a control treatment or comparing two doses of BUD were included. The primary outcome was maintenance of remission at one year. Secondary outcomes included mean change in CD activity index (CDAI), adverse events, and study withdrawal. Two independent investigators reviewed studies for eligibility and extracted the data. For the meta-analysis, a random or fixed effects model was chosen based on an assessment of heterogeneity. Results: Twelve studies were identified. Only one additional study was found since the previous review, which compared azathioprine with BUD. BUD 6 mg daily was no more effective than placebo for maintenance of remission at 3 months (RR 1.25, 95% CI 1.00-1.58), 6 months (RR 1.15, 95% CI 0.95-1.39), or 12 months (RR 1.13, 95% CI 0.94-1.35). BUD was neither more effective than azathioprine (RR 0.81, 95% CI 0.61-1.08), nor weaning doses of prednisolone for maintenance of remission at 12 months (RR 0.79; 95% CI 0.55-1.13), but was better than mesalamine (RR 2.51, 95% CI 1.03-6.12). BUD 3 mg daily was more effective than placebo at 3 months (RR 1.31, 95% CI 1.03-1.67). This benefit was not sustained at 6 months (RR 1.10; 95% CI 0.81-1.50), or 12 months (RR 1.04, 95% CI 0.84-1.30). The use of BUD 6 mg resulted in a modest improvement in CDAI scores at 12 months (WMD -23.49; 95% CI -46.65 to -0.32). Adverse events were more frequent in patients treated with 6 mg of BUD, compared with placebo (RR 1.49; 95% CI 1.01-2.19). Abnormal adrenocorticoid stimulation tests were seen more frequently in patients receiving both 6 mg daily (RR 2.88; 95% CI 1.72-4.82) and 3 mg daily (RR 2.73, 95% CI 1.34-5.57), compared with placebo. Patients receiving BUD were less likely to withdraw due to adverse events than those receiving azathioprine (RR 0.42; 95% CI 0.18-0.97). Conclusion: BUD is not more effective than placebo for maintenance of remission in CD. BUD results in a modest drop in CDAI scores; however, these benefits are offset by higher adverse events and more frequent adrenocorticoid suppression in patients receiving BUD. Lack of superiority of BUD compared to azathioprine is a new finding in this update. Disclosure - EK, AR, EIB - none. GGK - speaker for Merck, Schering-Plough, Abbott, and UCB Pharma; participated in advisory board meetings for Abbott, Merck, Schering-Plough, Shire, and UCB Pharma; research support from Abbott and Shire. ARO - advisory board for Janssen Canada, Abbvie Canada, Nestle Canada; research support (clinical trial site) from Janssen, Abbvie, Optimer US, Janssen US, Astra-Zeneca AHS - advisory boards for Merck, Abbott, and Shire; Speakers Bureau for Merck, Abbott, Shire, Aptalis, and Warner Chilcott; research support from Merck and Abbott CHS - advisory boards for Janssen Canada, Abbvie; Speaker for Janssen Canada; research support from Janssen Canada.

MTNF reverse signalling induced by TNFα antagonists involves a GDF-1 dependent pathway: implications for Crohn's disease

ObjectiveMechanisms of action (MoA) of anti-tumour necrosis factor α (TNFα) therapies in Crohn's disease (CD) may critically involve induction of immune cell apoptosis via membrane-bound TNFα (mTNFα) binding. Certolizumab pegol...

Nutrition in Inflammatory Bowel Disease

The diet of industrialized nations may contribute to the pathogenesis of both ulcerative colitis (UC) and Crohn disease (CD). Malnutrition is relatively unusual in UC, but in CD, which often affects the small intestine, it is frequent and may be severe. Nutrition support is therefore frequently indicated. First principles of artificial nutrition can be applied effectively using the gut whenever possible. Parenteral nutrition is generally required only in those with short bowel syndrome. An increasing literature (especially in pediatrics) favors the use of defined exclusive enteral nutrition (EN) in the primary treatment of active CD. Controlled trials are, however, lacking, and recommendations are accordingly not of the highest rank. It appears that in this context, simple polymeric regimens are usually sufficient, and there is currently insufficient evidence to make a strong recommendation for disease-specific feeds. In the maintenance of remission in CD, controlled data demonstrate that defined EN reduces the risk of relapse requiring steroid treatment. There are no data in support of primary nutrition therapy in UC either in management of the acute flare or in maintenance. In conclusion, nutrition therapy in adults with inflammatory bowel disease is probably both undervalued and underused, but the evidence base needs to be strengthened to confirm its efficacy, determine better those patients most likely to benefit, and optimize the regimens to be employed.

Comment On: Maintenance of Remission in Inflammatory Bowel Disease Using Omega-3 Fatty Acids (Fish Oil): A Systematic Review and Meta-Analyses.

The objective was to systematically review the efficacy and safety of n-3 (omega-3 fatty acids, fish oil) for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Electronic databases were searched systematically for randomized controlled trials of n-3 for maintenance of remission in inflammatory bowel disease (IBD). Studies of patients of any age group who were in remission at the time of recruitment and were followed for at least 6 months were included. The primary outcome was relapse rate at the end of the follow-up period. Nine studies were eligible for inclusion; six studies of CD (n = 1039) and three of UC (n = 138). There was a statistically significant benefit for n-3 in CD (relative risk [RR] 0.77; 95% confidence interval [CI] 0.61-0.98); however, the studies were heterogeneous (I 2 = 58%). The absolute risk reduction was -0.14 (95% CI: -0.25 to -0.02). Opinions may vary on whether this is a clinically significant effect. Two well-done studies with a larger sample size reported no benefit. A sensitivity analysis excluding a small pediatric study resulted in the pooled RR being no longer statistically significant. A funnel plot analysis suggested publication bias for the smaller studies. For UC, there was no difference in the relapse rate between the n-3 and control groups (RR 1.02; 95% CI: 0.51-2.03). The pooled analysis showed a higher rate of diarrhea (RR 1.36; 95% CI: 1.01-1.84) and symptoms of the upper gastrointestinal tract (RR 1.96; 95% CI: 1.37-2.80) in the n-3 treatment group. There are insufficient data to recommend the use of omega-3 fatty acids for maintenance of remission in CD and UC. ( Inflamm Bowel Dis. 2011;17:336-345).

Maintenance of remission in inflammatory bowel disease using omega-3 fatty acids (fish oil): A systematic review and meta-analyses

The objective was to systematically review the efficacy and safety of n-3 (omega-3 fatty acids, fish oil) for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Electronic databases were searched systematically for randomized controlled trials of n-3 for maintenance of remission in inflammatory bowel disease (IBD). Studies of patients of any age group who were in remission at the time of recruitment and were followed for at least 6 months were included. The primary outcome was relapse rate at the end of the follow-up period. Nine studies were eligible for inclusion; six studies of CD (n = 1039) and three of UC (n = 138). There was a statistically significant benefit for n-3 in CD (relative risk [RR] 0.77; 95% confidence interval [CI] 0.61-0.98); however, the studies were heterogeneous (I(2) = 58%). The absolute risk reduction was -0.14 (95% CI: -0.25 to -0.02). Opinions may vary on whether this is a clinically significant effect. Two well-done studies with a larger sample size reported no benefit. A sensitivity analysis excluding a small pediatric study resulted in the pooled RR being no longer statistically significant. A funnel plot analysis suggested publication bias for the smaller studies. For UC, there was no difference in the relapse rate between the n-3 and control groups (RR 1.02; 95% CI: 0.51-2.03). The pooled analysis showed a higher rate of diarrhea (RR 1.36; 95% CI: 1.01-1.84) and symptoms of the upper gastrointestinal tract (RR 1.96; 95% CI: 1.37-2.80) in the n-3 treatment group. There are insufficient data to recommend the use of omega 3 fatty acids for maintenance of remission in CD and UC.

Enteral nutrition for the maintenance of remission in Crohnʼs disease: a systematic review

This review study was designed to evaluate the efficacy of enteral nutrition (EN) for the maintenance of remission in patients with Crohn's disease (CD) who achieved medically or surgically induced remission. The Medline, Embase, Ovid, and Cochrane database search of literature was carried out to identify studies that reported the efficacy of EN for the maintenance of remission in CD. The main outcome measure was the occurrence of clinical or endoscopic relapse. Ten studies were included: one randomized controlled trial, three prospective non-randomized trials, and six retrospective studies. Elemental, semielemental or polymeric diets were used as an oral supplement or a nocturnal tube feeding in addition to ordinary foods. Comparing outcomes between patients who received EN and those who did not, the clinical remission rate was significantly higher in those with EN in all seven studies. In two studies, EN showed suppressive effects on endoscopic disease activity. In all four studies investigating impacts of the quantity of enteral formula on clinical remission, higher amounts of enteral formula were associated with higher remission rates: > or =30 kcal/kg ideal body weight/day (vs. <30 kcal/kg ideal body weight/day), > or =1200 kcal/day (vs. <1200 kcal/day), and > or =1600 kcal/day (vs. <1600 kcal/day). Quantitative pooling of studies was not feasible because of the diversity of interventions and outcome measures among the studies. Although the evidence level is not high, the available data suggest that EN may be useful for maintaining remission in patients with CD. Large randomized controlled trials are necessary to assess a definite efficacy of EN for the maintenance of remission.

Nutritional status and nutritional therapy in inflammatory bowel diseases

Underweight and specific nutrient deficiencies are frequent in adult patients with inflammatory bowel disease (IBD). In addition, a significant number of children with IBD, especially Crohn's disease (CD) have impaired linear growth. Nutrition has an important role in the management of IBD. In adults with CD, enteral nutrition (EN) is effective in inducing clinical remission of IBD, although it is less efficient than corticosteroids. Exclusive EN is an established primary therapy for pediatric CD. Limited data suggests that EN is as efficient as corticosteroids for induction of remission. Additional advantages of nutritional therapy are control of inflammation, mucosal healing, positive benefits to growth and overall nutritional status with minimal adverse effects. The available evidence suggests that supplementary EN may be effective also for maintenance of remission in CD. More studies are needed to confirm these findings. However, EN supplementation could be considered as an alternative or as an adjunct to maintenance drug therapy in CD. EN does not have a primary therapeutic role in ulcerative colitis. Specific compositions of enteral diets-elemental diets or diets containing specific components-were not shown to have any advantage over standard polymeric diets and their place in the treatment of CD or UC need further evaluation. Recent theories suggest that diet may be implicated in the etiology of IBD, however there are no proven dietary approaches to reduce the risk of developing IBD.

Selected Summary

Selected Summary

Probiotics for maintenance of remission in Crohn's disease

Crohn's disease (CD) is characterised by episodes of disease activity and symptom-free remission. Probiotics are microorganisms that can potentially benefit health, and have been evaluated as an alternate means of preventing relapse in patients with CD. To assess the effectiveness of probiotics for the maintenance of remission in CD. The following databases were searched: the Cochrane Database of Systematic Reviews (2005, Issue 3); the Cochrane Central Register of Controlled Trials (2005, Issue 3); the Cochrane IBD/FBD Group Trials Register (2005), MEDLINE (1966-2005); EMBASE (1980-2005); ISI Web of Knowledge (BIDS) 1981-2005; On-line clinical trials databases (2005); and review articles. Experts in the field were contacted for unpublished data. Randomised controlled trials of probiotic therapy. Two independent reviewers performed data extraction and assessment of methodological quality. The primary outcome was the relative risk (RR) of relapse after maintenance treatment (and 95% confidence intervals [CI]). Seven small studies were identified and varied according to probiotics tested, methodological quality and medication regimen. No studies were pooled for statistical analysis. There was no statistically significant benefit of E. coli Nissle for reducing the risk of relapse compared to placebo (RR 0.43, 95% CI 0.15 to 1.20), or Lactobacillus GG after surgically-induced remission (RR 1.58, 95% CI 0.30 to 8.40) or medically-induced remission (RR 0.83, 95% CI 0.25 to 2.80). There was no statistically significant benefit of probiotics for reducing the risk of relapse compared to maintenance therapy employing aminosalicylates or azathioprine (RR 0.67, 95% CI 0.13 to 3.30), and in this study the probiotic Lactobacillus GG was associated with adverse events. In children, there was there was no statistically significant difference between Lactobacillus GG and placebo for reducing the risk of relapse (RR 1.85, 95% CI 0.77 to 4.40). A small study using the yeast Saccharomyces boulardii demonstrated a difference that was not statistically significant in favour of probiotic combined with a reduced level of maintenance therapy over standard maintenance treatment alone (RR 0.17, 95% CI 0.02 to 1.23). There is no evidence to suggest that probiotics are beneficial for the maintenance of remission in CD. All of the included studies enrolled small numbers of patients and may have lacked statistical power to show differences should they exist. Larger trials are required to determine if probiotics are of benefit in Crohn's disease.