Remission In Crohn's Disease Research Articles

Efficacy and safety of autologous hematopoietic stem cell therapy for refractory Crohn's disease: A systematic review and meta-analysis.

Background:Autologous hematopoietic stem cell transplantation (HSCT) has been proposed for patients with refractory Crohn's disease (CD), but it is associated with mortality and adverse events; the balance between risks and benefits becomes significantly important in the therapy. The aim of the study was to assess the efficacy and safety of autologous HSCT therapy for refractory CD.Methods:We conducted a comprehensive search of PubMed, Embase, the Cochrane library, and Web of Science from inception to February 2017. The pooled estimate rates for efficacy and safety of refractory CD was performed by meta-analysis and reported according to the standard Cochrane guidelines and the PRISMA statement.Results:Four prospective uncontrolled cohort studies, 4 prospective case series, and 1 randomized controlled trial (RCT) were included. Autologous HSCT had a high rate of clinical and endoscopic remission in refractory CD [79.4%, 95% confidence interval (95% CI): 0.550–0.924; 81.9%, 95% CI: 0.603–0.931, respectively]. In the case of safety, it had a relatively high incidence rate of transplant-related mortality (6.4%, 95% CI: 0.028–0.140). A significant association was observed between autologous HSCT and the incidence of febrile neutropenia (83.2%, 95% CI: 0.632–0.934). About 18.5% (95% CI: 0.061–0.442) of patients with refractory CD reached clinical remission at mobilization phase. Besides, 82.1% (95% CI: 0.692–0.903) and 54.1% (95% CI: 0.261–0.797) patients with refractory CD could achieve immunosuppressive-free and steroid-free remission for at least 12 months after the therapy.Conclusion:Autologous HSCT could be a complicated treatment with relatively high mortality and significantly high efficacy for refractory CD, which should be used with caution. However, more RCTs of larger samples using refined and standardized protocols and longer period of follow-up time are needed to further assess the outcomes of autologous HSCT therapy.

Tu1700 - Depressive Psychological Status is Associated with Disease Exacerbation in Remissive Crohn's Disease Patients: A Prospective Observational Study

Tu1700 - Depressive Psychological Status is Associated with Disease Exacerbation in Remissive Crohn's Disease Patients: A Prospective Observational Study

CSF-1 regulates the function of monocytes in Crohn\u2019s disease patients in remission

During the flare-ups of Crohn’s disease (CD) patients, circulating leukocytes actively migrate toward the inflamed sites. During the remission, the lack of symptoms does not necessarily imply immunological remission. To decipher inflammatory mechanisms still operating during CD remission, we compared the expression of chemokine receptors on monocytes from CD and healthy donors (HD), and how these differences could modulate monocyte maturation and cytokine production. Flow cytometry analysis showed a higher expression of CCR5 on monocytes from CD patients than those from HD after 24 h. This CCR5 upregulation was associated with the spontaneous production of CSF-1 and IL-10. The higher expression of CCR5 on CD monocytes increased their migratory pattern in response to CCL5. Signaling through CCR5/CCL5 increased CD163 and HLA-DR expression and diminished TLR4-induced TNF-α and IL-6 secretion during monocyte differentiation. When we analyzed clinical parameters, patients treated with azathioprine had the highest CSF-1 levels and CCR5 expression. Our results suggest that monocytes from CD patients in remission produced high levels of CSF-1 that upregulate CCR5 expression. Consequently, monocytes differentiated in these conditions had a characteristic phenotype and lower production of inflammatory cytokines. The treatment with azathioprine could be responsible for this anti-inflammatory profile of monocytes.

P198 Dipeptidyl peptidase 4: a strong predictive marker of disease activity and treatment escalation in inflammatory bowel diseases

Background: Blood-based biomarkers provide a non-invasive estimation of the inflammatory burden in patients with inflammatory bowel diseases (IBD). We aimed to investigate the diagnostic and prognostic value of plasma Dipeptidyl peptidase 4 (DPP-4) in IBD patients. Methods: A total of 203 adult patients [n=149 IBD patients; n=42 healthy controls; n=12 immune controls - systemic lupus erythematosus (SLE) in remission] were prospectively recruited. Disease activity was assessed using the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD), the partial Mayo Score (pMS) for Ulcerative colitis (UC) and the Systemic Lupus Erythematosus Disease Activity Index for SLE. A multi-biomarker model was derived using logistic regression to evaluate predictors of disease activity and Cox regression to evaluate predictors of treatment escalation (disease outcome). Treatment escalation was defined as the need for escalation to immunomodulatory/biologic therapies or intestinal resection surgery, as a consequence of a disease flare. Results: Median DPP-4 values were lower in active CD vs CD in remission [1043ng/mL, interquartile range (IQR): 824–1345 vs 1685ng/mL, IQR: 1519–2237; p<0.001]; as well as in active UC vs UC in remission (1323ng/mL, IQR: 1064–1766 vs 2149ng/mL, IQR: 1616–2478; p<0.001). IBD patients in remission showed DPP-4 values significantly lower than healthy subjects; no differences were found between immune and healthy controls. In CD, DPP-4 correlated strongly with faecal calprotectin (FC) (r=−0.61, p<0.001), C-reactive protein (CRP) (r=−0.60, p<0.001) and HBI (r=−0.56, p<0.001). In UC, DPP-4 correlated moderately with FC (r=−0.31, p<0.05) and CRP (r=−0.32, p<0.05), and strongly with pMS (r=−0.52, p<0.001). The multivariable logistic regression model revealed that DPP-4 and CRP (in CD) and DPP-4, FC and CRP (in UC) are independent predictors of disease activity (Table 1). Table 1. Multiple logistic regression model of predictors of disease activity At follow-up (median 578 days, IQR: 426–688), DPP-4 and CRP showed to independently predict treatment escalation in both CD and UC (Table 2). Table 2. Cox proportional hazards model for predictive factors of treatment escalation At 1 year, the proportion of patients who needed treatment escalation was 66% in CD and 41% in UC, if ≥2 biomarkers criteria were met. Conclusions: An activity assessment model and a prognostic model that combines DPP-4 and other biomarkers accurately predicts IBD activity and an aggressive disease course.

P775 Fibre intake is associated with microbiome changes in pediatric Crohn's disease patients following remission induction with exclusive enteral nutrition

Background: Changes in gut microbiome community structure are associated with the development of Crohn's Disease (CD) and can be altered by environmental factors such as diet. Exclusive enteral nutrition (EEN) can induce disease remission in more than 80% of pediatric CD patients. However, the mechanism of EEN effectiveness remains unclear and evidence-based dietary recommendations for remission maintenance after EEN cessation do not exist. We aimed to assess the influence of dietary fibre intake on microbiome composition and sustained remission. Methods: We conducted a cross-sectional analysis of 11 pediatric CD patients aged 11–17 years old who are participants in an ongoing study of microbiome changes in response to EEN. Participants had returned to their regular ad libitum diet for at least 3 months following 12-week EEN therapy, and completed a 79-item validated food frequency questionnaire (FFQ) to assess their fibre intake. Clinical sustained remission (SR) was indicated by weighted Pediatric Crohn's Disease Activity Index (wPCDAI) <12.5 by 6 month follow-up, otherwise participants were classified as non-sustained remission (NSR). 16S rRNA from participant stool samples collected at 12-week intervals was analysed using QIIME to assess changes in gut microbial diversity at time of EEN and following return to regular diet. Results: The dietary data revealed general low fibre intake (only 1 of 11 respondents consumed recommended amount of daily dietary fibre), so participants were classified as “higher fibre” if they consumed at least half the daily fibre recommendation for their age and sex, and “lower fibre” if they did not. Microbial beta diversity was significantly lower in patients consuming lower fibre compared to those consuming higher fibre (p=0.04, ANOSIM). There were no significant differences in alpha or beta diversity between patients consuming <600g of oral solid food (n=3) at time of FFQ and those consuming >600g. Microbial alpha diversity (Chao-1) analysis of patients' stool samples, after return to regular diet, showed the lowest gut microbial richness in patients who achieved remission with EEN but experienced disease flare (NSR) flare by 6 months follow-up (n=3), compared to EEN primary non-responders (n=2) and those in SR (n=4). Conclusions: Lower fibre intake is associated with decreased gut microbial diversity in pediatric CD patients after completing induction treatment with EEN. Persistence of decreased gut microbiome diversity with return to regular diet after EEN may indicate increased risk of disease flare. Further longitudinal analysis of microbiome changes associated with return to an oral diet after EEN are required to inform dietary therapy recommendations for maintenance of remission in pediatric CD.

P622 Efficacy of probiotics in inflammatory bowel disease: systematic review and meta-analysis

Abstract Background: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. We performed a systematic review and meta-analysis to examine the efficacy of probiotics in IBD. Methods: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). Results: The search identified 12,251 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission = 0.86; 95% CI 0.68–1.08). Figure 1. Forest plot of randomised controlled trials reporting the efficacy of probiotics versus placebo in inducing remission in active UC, or in preventing relapse in quiescent UC. However, when only trials of VSL#3 were considered there appeared to be a benefit (RR =0.74; 95% CI 0.63–0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR =1.02 (95% CI 0.85 to 1.23). Figure 2. Forest plot of randomised controlled trials reporting the efficacy of probiotics versus 5-aminosalicylates in Inducing remission in active UC, or in preventing relapse in quiescent UC. There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing endoscopic or clinical relapse of CD after surgically induced remission. Figure 3. Forest plot of randomised controlled trials reporting the efficacy of probiotics versus placebo in inducing remission in active CD, or in preventing relapse in quiescent CD. Conclusions: VSL#3 appears to be effective in inducing remission in active UC, and probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. However, the efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known.

P763 Fucosyltransferase 2 non-secretor status in Crohn's disease: a prospective observational analysis

Background: The FUT2 gene encodes fucosyltransferase 2 (FUT2), regulating intestinal antigen secretion and bacterial adherence. FUT2 homozygous mutations (FUT2M) and subsequent non-secretor status is associated with Crohn's disease (CD). A nucleotide polymorphism encoding a nonsense variant may predispose to CD by disrupting bacterial adherence or mucin fucosylation. This alters bacterial and mucous protection against pathogens, causing immune disequilibrium and mucosal inflammation. FUT2 products also interact with the IL 12/23 inflammatory pathways. Supporting genome wide association studies strongly associate homozygous FUT2 SNPs in strong linkage disequilibrium (LD) (rs602662 (A), rs676388 (C), rs492602 (G), rs504963 (A), rs601338 (A), rs485186 (G)), non-secretion, and CD. rs601338 (W143X) is the common null allele in Caucasians associated with the ABO non-secretory phenotype. Methods: We conducted a cross-sectional observational study of consecutive adult CD outpatients at the McGill University Health Center (2013–2015). Clinical and biochemical data were prospectively collected at a single routine office visit. We analyzed associations between CD and FUT2 mutation status. Results: Sixty-two CD patients were recruited. FUT2M homozygotes (rs602662, rs601338 or any mutation in LD) were detected in 27% of CD (17/62). Compared to Wild type (n=18), CD FUT2M homozygotes (n=17) had less penetrating CD (18% vs. 56%, p=0.02) and higher clinical remission without biologic or immunomodulator therapy (47% vs 6%, p=0.006). The latter was not observed in heterozygotes (22%, n=27, p=0.15). CD FUT2M homozygotes had similar disease location in the ileum (L2 p=0.31) and colon (L1, L3, p=0.56). Similarly, patients with homozygous rs601338 (n=15) had increased clinical remission rates without biologic or immunomodulator therapy (53% vs 5%, p=0.0016) compared to patients with wild type status (n=19). This was not observed in heterozygotes (24%, n=25, p=0.09). Both rs601338 homozygotes (20%) and heterozygotes (24%) had less penetrating disease than Wild type (53%, p=0.0495, 0.0478). rs601338 homozygotes (67%) but not heterozygotes (56%) had more luminal phenotype compared to non-mutants (32%, p=0.042). Conclusions: FUT2 homozygous mutations in CD was associated with a milder disease course: lower rates of penetrating disease and higher rates of remission without need for biologic or immunomodulator therapy. FUT2 may play a role in the natural history of CD through mofification of expression of adherence molecules and gut dysbiosis. Further studies are needed to confirm these findings.

Exclusive Enteral Nutrition Induces Remission in Pediatric Crohn's Disease via Modulation of the Gut Microbiota.

Exclusive enteral nutrition (EEN) has been proven to be effective and safe in treating pediatric Crohn's disease (CD). EEN induces pediatric CD remission possibly through three pathways: (1) direct anti-inflammatory effects, (2) improved epithelial barrier function, and (3) modulation of the gut microbiota. Recent studies have demonstrated that modulation of the gut microbiota plays a major role in EEN-induced remission. Variations of microbial components, which directly influence the diversity and metabolic functions of the gut microbiota, are closely associated with the immunological conditions of the gut and the susceptibility to diseases. The reduction of proinflammatory microbial components and harmful microbial metabolites after EEN treatment greatly decreases the inflammatory injuries of the gut.

Platelets Toll-like receptor-4 in Crohns disease.

Platelets are activated in Crohn's disease (CD) and interplay with leukocytes. Engagement of Toll-like receptor-4 (TLR-4), which is expressed in human platelets, may be involved in crosstalks between platelets and leukocytes leading to their mutual activation for host defense. Human neutrophil peptides (HNPs), lipoprotein binding peptides, and sCD14 were determined by enzyme-linked immunosorbent assays in 42 patients with active CD, in 43 patients with CD in remission, and in 30 healthy individuals. Neutrophil-platelet aggregates and binding of the TLR-4 monoclonal antibody to platelets were determined by flow cytometry. Levels of HNPs were higher in patients with CD than in controls (P = 0.0003 vs. active CD and P = 0.01 vs. CD in remission). Likewise, neutrophils with adhering platelets were higher in patients with active CD than in controls (P = 0.004). Binding of the TLR-4 antibody in patients with active CD was similar to that in controls, while patients in remission had significantly higher binding capacities (P = 0.59 and P = 0.003). Incubation of plasma from patients with active disease or patients in remission with platelets from healthy controls confirmed lower binding of the TLR-4 antibody in the presence of plasma from active diseased patients compared to controls (P = 0.039), possibly due to high levels of lipopolysaccharides, as suggested by high levels of sCD14 and lipoprotein binding protein. Our study indicates involvement of platelet TLR-4 in enhancing the secretion of antimicrobial peptides from neutrophils. While platelet aggregation can be due to a variety of mechanisms in inflammatory disease, the mutual activation of platelets and neutrophils may augment host defense.

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study.

To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD). This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000IU daily (n=18) compared to 1000IU daily (n=16) for 12months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores. High-dose vitamin D3 at 10,000IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5nmol/L [standard deviation (SD) 11.7nmol/L] to 160.8nmol/L (SD 43.2nmol/L) (p=0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p=0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000IU daily (3/8 or 37.5%) (p=0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3. Oral supplementation with high-dose vitamin D3 at 10,000IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted. CLINICALTRIALS. NCT02615288.

Downregulation of MicroRNA-21 in Colonic CD3+ T Cells in UC Remission.

In active inflammatory bowel disease (IBD), microRNA expression profiling consistently features disease-specific signatures, and microRNA-21 (miR-21) has been shown to be upregulated in the inflamed colon of patients with active ulcerative colitis (UC). However, the cellular sources of miR-21 expression in IBD tissues have not yet been identified. We sought to determine the expression levels of miR-21 and one of its downstream target genes, programmed cell death 4 (PDCD4), in CD3 T cells isolated from the colonic mucosa of patients with active IBD, inactive IBD, and non-IBD controls. Colonic biopsies were treated with collagenase V. CD3 T cells were isolated using MACS CD3 positive selection. Total RNA was converted to cDNA. Real-time PCR reactions were performed with PCR primers for miR-21, SNORD95, PDCD4, and GAPDH. The expression of miR-21 was statistically significantly downregulated in CD3 T cells from patients with UC in remission as compared to active disease (P = 0.0193). miR-21 negatively regulates PDCD4 expression. As predicted, the mRNA level of PCDC4 in CD3 T cells was upregulated in UC and Crohn's disease in remission as compared to active disease (UC active versus UC remission: P = 0.0008, Crohn's disease active versus Crohn's disease remission: P = 0.0215) and in patients with UC in remission as compared to healthy controls (P = 0.0226). Although miR-21 expression is downregulated, PDCD4 is upregulated in CD3 T cells during the remission phase of UC. Our results indicate that miR-21 and related pathways in colonic T cells may play a role in limiting pathogenic T-cell responses and may constitute future target candidates to induce remission in UC.

Emotional and personality features of patients with irritable bowel syndrome and bowel inflammatory diseases

To conduct a comparative analysis of the emotional and personality characteristics of patients with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) in remission with IBS-like symptoms. This study carried out based at a specialized gastroenterology clinic in the period from 2010 to 2015 included 125 patients with IBS (IBS-D - 46, IBS-C - 20, IBS-M - 59) and 37 patients with IBD in remission: Crohn's disease (CD) - 11 and ulcerative colitis (UC) -26 patients. The levels of depression (Beck questionnaire), urgent and personal anxiety (Spielberger questionnaire), the degree of alexithymia (Toronto scale) as well as the severity of psychopathology and behavioral symptoms (PBS) were estimated. Patients with IBS were not significantly different from those with IBD in remission with IBS-like symptoms in terms of depression, actual anxiety, alexithymia and PBS. Only the index of personal anxiety was significantly higher in the group of patients with IBS compared with IBD in remission with IBS-like symptoms (p = 0.0376). Men with IBS exhibited significantly higher actual anxiety than men with IBD (p = 0.04). Maximum severity of depression, anxiety and alexithymia was documented in the locking version of IBS (IBS-C) in comparison with other variants of IBS (p <0.05). Patients with CD in remission are characterized by higher rates of depression and alexithymia compared to UC (p <0.05). Behavioural disorders are most pronounced in the diarrheal variant of IBS and CD. A higher personal anxiety was observed in patients with IBS compared to those in remission of IBD with IBS-like symptoms although other parameters were not significantly different. Patients with IBS-C were characterized by more pronounced manifestations of emotional and personality disorders. More severe emotional and behavioral disorders distinguish CD from UC.

Silent Crohn's Disease Predicts Increased Bowel Damage During Multiyear Follow-up: The Consequences of Under-reporting Active Inflammation.

Patients with Crohn's disease (CD) in clinical remission with elevated C-reactive protein (CRP) have been labeled "silent CD" and have increased 2-year hospitalization rates when compared with asymptomatic patients with no biochemical evidence of inflammation. The risk of cumulative bowel damage in patients with silent CD is unknown. Observational study of patients with CD prospectively followed in a tertiary referral natural history registry. Consecutive patients with CD in clinical remission (Harvey-Bradshaw Index ≤ 4) with good quality of life (short inflammatory bowel disease questionnaire score ≥ 50), and same day CRP measurement at first encounter, followed for a minimum of 4 years formed the study population. Disease trajectory was determined using change in Lémann Index as a measure of bowel damage. A total of 185 patients with CD (median age 42 years; 51.4% men) were included in the study. CRP elevation was observed in 43 (23%) patients (Silent CD cohort). Majority of them showed worsening disease trajectories based on change in Lémann Index when compared with asymptomatic patients with normal CRP (65% versus 36%, P < 0.0001). Multinomial logistic regression analysis demonstrated that elevated CRP was independently associated with 7-fold higher odds (odds ratio = 6.93, P < 0.0001) of having worse disease trajectories when compared with stable disease trajectories. Two-thirds of patients with CD in clinical remission, while demonstrating elevated CRP, will develop bowel damage over the ensuing years, despite feeling well. These patients with silent CD are an "at-risk" group who warrant further investigation to prevent development of disease-related complications.

High Vitamin D-Binding Protein Concentration, Low Albumin, and Mode of Remission Predict Relapse in Crohn's Disease.

Vitamin D (25(OH)D) deficiency occurs in active Crohn's disease (CD) and may be secondary to reduced sunlight exposure and oral intake. Vitamin D-binding protein (VDBP) levels, however, fluctuate less with season and sunlight. The aim, therefore, was to examine patients with CD in remission and determine any associations between VDBP, serum 25(OH)D, and the calculated free 25(OH)D concentrations with the risk of disease flare. Subjects were identified from prospectively maintained inflammatory bowel disease databases at 3 teaching hospitals in Australia. Patients were in steroid-free clinical remission at the time of blood draw and were followed for at least 12 months. Total and epimer-25(OH)D3, VDBP concentrations, and genotypes were determined. A total of 309 patients with CD (46% men) met the inclusion criteria. A disease flare occurred in 100 (32.4%). Serum 25(OH)D3 was deficient (<50 nmol/L) in 36 (12%) and insufficient (50-75 nmol/L) in 107 (35%) patients. Total, free, and epimer-25(OH)D3 serum levels did not predict disease flare. Higher VDBP concentrations, however, significantly correlated with increased risk of disease flare (hazard ratio 1.2, 95% CI, 1.0-1.5). On multivariate analysis, VDBP concentration, low albumin, and medication-induced remission were significantly more associated with disease flare. VDBP genotypes were significantly associated with 25(OH)D and VDBP concentrations but not disease flare. Vitamin D deficiency was uncommon in our patients with CD in remission, and serum 25(OH)D3 did not predict disease flare, whereas higher VDBP concentrations were significantly associated with disease flare. Further investigations to explore the possible mechanisms for this association are warranted.

Examining Patient Decision-Making Surrounding Biologic Therapies in Inflammatory Bowel Disease: Insights from a Conjoint Analysis Survey

Introduction: Recent drug approvals have increased the availability of biologic therapies for inflammatory bowel disease (IBD). The growing number of biologics has made it increasingly difficult for patients to navigate treatment options and to ultimately select the most appropriate therapy. In this study, we examined patient decision-making surrounding IBD biologic therapies using conjoint analysis, a form of tradeoff analysis that determines how respondents make complex decisions by presenting them with competing product profiles. Methods: We performed a conjoint analysis survey that quantified the relative importance of 9 biologic therapy attributes (see Figure) in the decision-making process. We partnered with a survey research firm to recruit IBD patients to complete the survey. The conjoint analysis software determined each individual's preferences by calculating importance factors called partworth utilities for each biologic therapy attribute (higher part-worth utility=more important factor in decision-making process). We also conducted regression analyses to determine if patient demographics and IBD characteristics (e.g. type of IBD, severity, etc.) predicted importance of tested attributes. Results: 274 and 269 patients with ulcerative colitis (UC) and Crohn's disease (CD), respectively, completed the conjoint survey (Table). The primary determinants of decision-making differed between UC and CD patients as shown in the Figure. In regression analyses, demographic and IBD characteristics largely did not predict part-worth utility scores for the tested attributes; the main exception was IBD type. When compared to UC patients, those with CD were significantly more likely to attribute more importance to short-term improvement rates, risk of serious infection, and tolerability of side effects in the decision-making process (all p < .01). Conversely, those with UC were more likely to value mode of administration, long-term remission rates, and rash vs. CD patients (all p < .01). No differences were seen between UC and CD patients for lymphoma risk, fatigue, or mechanism of action (all p>.05). Conclusion: The determinants of decision-making surrounding IBD biologic therapies varied considerably between those with UC and CD. Moreover, patient demographics and IBD characteristics poorly predicted decision-making. This suggests the benefit of tailored decision tools to support patient choice of IBD therapy, which may be accessed either online or via mobile devices.Table 1: Study population demographics.Figure 1

COMBINATION THERAPY OF MESENCHYMAL STROMAL CELLS AND INFLIXIMAB IN UNCOMPLICATED (LUMINAL) CROHN DISEASE

AIMS. To investigate the efficacy of combination therapy using bone marrow-derived mesenchymal stromal cells (MSC) and Infliximab (IFX) to achieve «deep remission» in patients with luminal Crohn disease (CD). METHODS. Our study included 72 patients (19-62 y old) (Ме=29) with luminal CD. Patients ini group (n=21) received standard 5-aminosalicylic acid (5-ASA) and glucocorticosteroids (GCS) therapy in combination with MSC. Patients in 2 group (n=32) were prescribed anti-cytokine therapy IFX. Patients in 3 group (n=19) received MSC and IFX. RESULTS. Clinical, immunobiological and hystological results (C-reactive protein-CRP, fecal calprotectin-FCP, Gebs scale) showed more significant decrease of local and systemic inflammation activity in 3 group of patients. During 3-year follow-up we observed the longer duration of remission in patients, received MSC and IFX compared to 1 group of patients (р=0,04) and 2 group of patients (р=0,038). CONCLUSIONS. Combination therapy of bone marrow-derived MSC and IFL provides «deep remission» in patients with luminal CD and has higher prognostic value in duration of CD remission period.

Mucosal MicroRNAs Expression Profiles before and after Exclusive Enteral Nutrition Therapy in Adult Patients with Crohn's Disease.

MicroRNAs (miRNAs) have been shown to be important for the pathogenesis of Crohn’s disease (CD). Exclusive enteral nutrition (EEN) is an effective therapy for inducing remission in CD. We aimed to investigate the alteration of miRNAs expression profile in the terminal ileal mucosa of CD patients before and after EEN. Twenty-five patients and ten healthy individuals were included. MiRNAs expression profile was firstly assessed using microarray technology and then validation was performed by qRT-PCR. The correlations between miRNAs and CD activity index (CDAI) score and serum C–reactive protein (CRP) level were also evaluated. Microarray analysis showed that mucosal miRNAs expression profile after EEN therapy was significantly changed compared with inflamed mucosa before treatment, and was most similar to the healthy one among all CD groups. Altered expressions of hsa-miR-192-5p, hsa-miR-423-3p, hsa-miR-99a-5p, hsa-miR-124-3p, hsa-miR-301a-5p, hsa-miR-495-5p, and hsa-let-7b-5p were confirmed by qRT-PCR. hsa-let-7b-5p was significantly correlated with serum CRP levels before and after EEN treatment (r = −0.518, p = 0.008, and r = −0.569, p = 0.003). Our study showed EEN induction therapy was associated with a trend for normalizing of the mucosal miRNAs expression profile, and expression of mucosal hsa-let-7b-5p was correlated with serum CRP level in patients with CD.

Inflammation-driven malnutrition: a new screening tool predicts outcome in Crohn's disease.

Malnutrition is a frequent feature in Crohn's disease (CD), affects patient outcome and must be recognised. For chronic inflammatory diseases, recent guidelines recommend the development of combined malnutrition and inflammation risk scores. We aimed to design and evaluate a new screening tool that combines both malnutrition and inflammation parameters that might help predict clinical outcome. In a prospective cohort study, we examined fifty-five patients with CD in remission (Crohn's disease activity index (CDAI) <200) at 0 and 6 months. We assessed disease activity (CDAI, Harvey-Bradshaw index), inflammation (C-reactive protein (CRP), faecal calprotectin (FC)), malnutrition (BMI, subjective global assessment (SGA), serum albumin, handgrip strength), body composition (bioelectrical impedance analysis) and administered the newly developed 'Malnutrition Inflammation Risk Tool' (MIRT; containing BMI, unintentional weight loss over 3 months and CRP). All parameters were evaluated regarding their ability to predict disease outcome prospectively at 6 months. At baseline, more than one-third of patients showed elevated inflammatory markers despite clinical remission (36·4 % CRP ≥5 mg/l, 41·5 % FC ≥100 µg/g). Prevalence of malnutrition at baseline according to BMI, SGA and serum albumin was 2-16 %. At 6 months, MIRT significantly predicted outcome in numerous nutritional and clinical parameters (SGA, CD-related flares, hospitalisations and surgeries). In contrast, SGA, handgrip strength, BMI, albumin and body composition had no influence on the clinical course. The newly developed MIRT was found to reliably predict clinical outcome in CD patients. This screening tool might be used to facilitate clinical decision making, including treatment of both inflammation and malnutrition in order to prevent complications.

Impact on Life Expectancy of Withdrawing Thiopurines in Patients with Crohn's Disease in Sustained Clinical Remission: A Lifetime Risk-Benefit Analysis.

ObjectiveLong-term treatment with thiopurines is associated with a decreased risk of Crohn’s disease (CD) flare but an increased risk of various cancers depending on gender, age, and presence of extensive colitis. We evaluated risks and benefits of withdrawing thiopurines in patients with CD in prolonged remission.MethodsWe developed a Markov model assessing risks and benefits of withdrawing thiopurines compared to continuing thiopurines in a lifetime horizon. The model was stratified by age (35 and 65 years old at thiopurine withdrawal), gender and presence of extensive colitis. Parameter estimates were taken from French cohorts and hospital databases, cancer and death national registries and published literature. Life expectancy, rates of relapse, serious adverse events, and causes-of-death were evaluated.ResultsIn patients without extensive colitis, continuing thiopurines increased life expectancy up to 0.03 years for 35 year-old men and women but decreased life expectancy down to 0.07 years for 65 year-old men and women. Withdrawal strategy became the preferred strategy at 40.6 years for men, and 45.7 years for women without extensive colitis. In patients with extensive colitis, continuation strategy was the preferred strategy regardless of age. Risk-benefit analysis was not modified by duration of CD activity.ConclusionsFactors determining life expectancy associated with withdrawal or continuation of thiopurines in patients with CD and in sustained clinical remission vary substantially according to gender, age and presence of extensive colitis. Individual decisions to continue or withdraw thiopurines in patients with CD in sustained remission should take into account these parameters.

Complete remission of Crohn's disease after high-dose alpha-interferon treatment for malignant melanoma

Complete remission of Crohn's disease after high-dose alpha-interferon treatment for malignant melanoma