Project description:Crohn's disease (CD) patients who undergo ileocolonic resection (ICR) typically have disease recurrence at the anastomosis which has been linked with a gut dysbiosis. The aims of this study were to define the mucosa-associated microbiota at the time of ICR and to determine if microbial community structure at the time of surgery was predictive of future disease relapse. Ileal biopsies were obtained at surgery and after 6 months from CD subjects undergoing ICR. Composition and function of mucosal-associated microbiota was assessed by 16S rRNA sequencing and PICRUSt analysis. Endoscopic recurrence was assessed using the Rutgeerts score. Analysis of mucosal biopsies taken at the time of surgery showed that decreased Clostridiales together with increased Enterobacteriales predicted disease recurrence. An increase in the endospore-forming Lachnospiraceae from surgery to 6 months post-ICR was associated with remission. A ratio of 3:1 between anaerobic endospore-forming bacterial families and aerobic families within the Firmicutes phylum was predictive of maintenance of remission. Gut recolonization following ICR is facilitated by microbes which are capable of either aerobic respiration or endospore formation. The relative proportions of these species at the time of surgery may be predictive of subsequent microbial community restoration and disease recurrence.
Project description:BACKGROUND: The relapse rate after steroid induced remission in Crohn's disease is high. AIMS: To test whether oral pH modified release budesonide (3 x 1 mg/day) reduces the relapse rate and to identify patient subgroups with an increased risk of relapse. METHODS: In a multicentre, randomised, double blind study, 179 patients with steroid induced remission of Crohn's disease received either 3 x 1 mg budesonide (n = 84) or placebo (n = 95) for one year. The primary study aim was the maintenance of remission of Crohn's disease for one year. RESULTS: Patient characteristics at study entry were similar for both groups. The relapse rate was 67% (56/84) in the budesonide group and 65% (62/95) in the placebo group. The relapse curves in both groups were similar. The mean time to relapse was 93.5 days in the budesonide group and 67.0 days in the placebo group. No prognostic factors allowing prediction of an increased risk for relapse or definition of patient subgroups who derived benefit from low dose budesonide were found. Drug related side effects were mild and no different between the budesonide and the placebo group. CONCLUSION: Oral pH modified release budesonide at a dose of 3 x 1 mg/day is not effective for maintaining steroid induced remission in Crohn's disease.
Project description:Background & aimsCrohn'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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.
Project description:BackgroundPartial enteral nutrition (PEN) may be helpful for the maintenance of remission in pediatric Crohn's disease patients.AimsTo evaluate the efficacy of PEN treatment for preventing clinical relapse.MethodsWe retrospectively assessed 42 pediatric Crohn's disease patients who entered clinical remission on 4-12 weeks of exclusive enteral nutrition (EEN) and were maintained on PEN as a supplementary diet. We evaluated the efficacy of the treatment at different time points using the weighted Pediatric Crohn Disease Activity Index (wPCDAI), Physician Global Assessment, laboratory parameters, and growth of each patient. Additionally, we assessed the use of concomitant medications.ResultsThe median length of remission with PEN was 6 (0-36) months. Patients' remission was maintained on PEN without concomitant medications for a median time of zero months (0-16). The mean body mass index in the PEN group increased from 18.1 to 18.8 after six months of PEN. The median wPCDAI decreased from 30 at diagnosis to 5.0 after EEN and increased to 7.5 after three months of PEN. Overall, the median wPCDAI decreased by 26.2.ConclusionsPEN treatment was partially effective in maintaining remission and was able to increase BMI and lower wPCDAI. Most patients required concomitant medication after PEN initiation.
Project description:ObjectivesUseful indices to determine whether to reduce the dose of 5-aminosalicylic acid (5-ASA) in patients with ulcerative colitis (UC) during remission remain unclear. We aimed to analyze the rate and risk factors of relapse after reducing the dose of oral 5-ASA used for maintenance therapy of UC.MethodsUC patients whose 5-ASA dose was reduced in clinical remission (partial Mayo score of ≤ 1) at our institution from 2012 to 2017 were analyzed. Various clinical variables of patients who relapsed after reducing the dose of oral 5-ASA were compared with those of patients who maintained remission. Risk factors for relapse were assessed by univariate and multivariate logistic regression analyses. Cumulative relapse-free survival rates were calculated using the Kaplan-Meier method.ResultsA total of 70 UC patients were included; 52 (74.3%) patients maintained remission and 18 (25.7%) patients relapsed during the follow-up period. Multivariate analysis indicated that a history of acute severe UC (ASUC) was an independent predictive factor for clinical relapse (p = 0.024, odds ratio: 21, 95% confidence interval: 1.50-293.2). Based on Kaplan-Meier survival analysis, the cumulative relapse-free survival rate within 52 weeks was 22.2% for patients with a history of ASUC, compared with 82.0% for those without. the log-rank test showed a significant difference in a history of ASUC (p < 0.001).ConclusionsDose reduction of 5-ASA should be performed carefully in patients who have a history of ASUC.
Project description:BACKGROUND/AIMS:This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD). METHODS:Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220-450; high-sensitivity [hs]-C-reactive protein [CRP] ?3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8-26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ?70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored. RESULTS:Mean adalimumab serum concentrations during the induction phase were 13.9-18.1 µg/mL (160/80 mg group) and 7.5-9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups. CONCLUSIONS:Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported.
Project description:Background and aimsThe efficacy of 5-aminosalicylic acid (5-ASA) in the long-term outcome of Crohn's disease (CD) patients was uncertain. This study aimed to evaluate the efficacy of the 5-ASA in preventing disease behavior progression and intestinal resection in CD patients.MethodsCD patients were prospectively enrolled from January 2008 to September 2019 in Xijing Hospital. Disease behavior progression was defined as the development of stricturing (B2) or penetrating disease (B3) in patients with nonstricturing/nonpenetrating disease (B1) at diagnosis. Cox regression analyses were used to investigate the associations between disease location progression, disease behavior progression, and intestinal resection and multiple covariates.ResultsIn total, 122 CD patients were followed up for 4.3 years. At the time of diagnosis, disease location was ileal in 19.7% (24/122), colonic in 41.0% (50/122), and ileocolonic in 39.3% (48/122). A total of 87 (71.3%) patients had B1 at diagnosis. The disease behavior progression and intestinal resection rates were 42.5% (37/87) and 29.5% (36/122). The use of 5-ASA reduced the risk of disease behavior progression (HR 0.30, 95% CI 0.14-0.61, P = 0.001) and intestinal resection (HR 0.33, 95% CI 0.17-0.90, P = 0.027) in colonic and ileocolonic CD patients. Patients who presented with ileal disease at diagnosis did not have the same protective effects when taking 5-ASA (P > 0.05).ConclusionsThe use of 5-ASA could improve the long-term outcome of CD patients with colon involvement. The result emphasized the importance of early use of 5-ASA in the daily management of colonic involved CD.