Adult Crohn's Disease Patients Research Articles

Increased colonic expression of ACE2 associates with poor prognosis in Crohn\u2019s disease

The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. We examined the expression of colonic ACE2 in 67 adult CD and 14 NIBD control patients using RNA-seq and quantitative (q) RT-PCR. We validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan–Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. Colonic ACE2 expression was significantly higher in a subset of adult CD patients which was defined as the ACE2-high CD subset. IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of CD diagnosis, and a Cox regression analysis found that high ACE2 levels is an independent risk factor for surgery (OR 2.17; 95% CI, 1.10–4.26; p = 0.025). Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that can impact CD disease-related outcomes.

Systematic review: efficacy of escalated maintenance anti-tumour necrosis factor therapy in Crohn's disease.

Loss of response to anti-TNF agents is a common clinical problem. Dose escalation may be effective for reestablishing clinical response in Crohn's disease (CD). To perform a systematic review assessing the efficacy of escalated maintenance anti-TNF therapy in CD. EMBASE, MEDLINE, Web of Science, and CENTRAL databases were searched for English language publications through to April 25, 2021. Full-text articles evaluating escalated maintenance treatment (infliximab or adalimumab) in adult CD patients were included. A total of 4733 records were identified, and 68 articles met eligibility criteria. Rates of clinical response (33%-100%) and remission (15%-83%) after empiric dose escalation for loss of response to standard anti-TNF therapy were high but varied across studies. Dose intensification strategies (doubling the dose versus shortening the therapeutic interval) were similarly efficacious. Dose-escalated patients tended to have higher serum drug levels compared to those on standard dosing. An exposure-response relationship following dose escalation was found in a number of observational studies. Randomised controlled trials comparing therapeutic drug monitoring (TDM) to empiric treatment intensification have failed to reach their primary end-points. Strategies including Bayesian dashboard-dosing and early treatment escalation targeting biomarker normalisation were found to be associated with improved long-term outcomes. Empiric escalation of maintenance anti-TNF therapy can recapture clinical response in a majority of patients with secondary loss of response to standard maintenance doses. Proactive optimisation of maintenance dosing might prolong time to loss of response in some patients.

Ultrasonography Tight Control and Monitoring in Crohn’s Disease During Different Biological Therapies: A Multicenter Study

Bowel ultrasonography (BUS) is a noninvasive tool for evaluating bowel activity in Crohn's disease (CD) patients. Aim of our multicenter study was to assess whether BUS helps to monitor intestinal activity improvement/resolution following different biological therapies. Adult CD patients were prospectively enrolled at 16 sites in Italy. Changes in BUS parameters [i.e. bowel wall thickening (BWT), lesion length, echo pattern, blood flow changes and transmural healing (TH: normalization of all BUS parameters)] were analyzed at baseline and after 3, 6 and 12 months of different biological therapies. One hundred eighty-eight out of 201 CD patients were enrolled and analyzed (116 males [62%]; median age 36 years). Fifty-five percent of patients were treated with adalimumab, 16% with infliximab, 13% with vedolizumab and 16% with ustekinumab. TH rates at 12 months were 27.5% with an NNT of 3.6. TH at 12 months after adalimumab was 26.8%, 37% after infliximab, 27.2% after vedolizumab and 20% after ustekinumab. Mean BWT improvement from baseline was statistically significant at 3 and 12 months (P < .0001). Median Harvey-Bradshaw index, C-reactive protein and fecal calprotectin decreased after 12 months from baseline (P < .0001). Logistic regression analysis showed colonic lesion was associated with a higher risk of TH at 3 months and a greater BWT at baseline was associated with a lower risk of TH at 3 months [P= .03 (OR 0.70, 95% CI 0.50-0.97)] and 12 months [P= .01 (OR 0.58, 95% CI 0.38-0.89)]. At 3 months therapy optimization during the study was the only independent factor associated with a higher risk of no ultrasonographic response [P= .02 (OR 3.34, 95% CI 1.18-9.47)] and at 12 months disease duration [P= .02 (OR 3.03, 95% CI 1.15-7.94)]. Data indicate that BUS is useful to monitor biologics-induced bowel activity improvement/resolution in CD.

Biosimilar infliximab versus originator in Crohn's disease anti-TNF-α naïve and non-naïve patients.

IntroductionData comparing response to originator and biosimilar infliximab in anti-TNF-α naïve and non-naïve Crohn’s disease patients is limited.AimTo assess the efficacy, safety, and tolerability of a biosimilar infliximab in comparison to the originator drug in anti-TNF-α naïve and non-naïve Crohn’s disease patients. Data comparing response in those two groups of patients are limited.Material and methodsThis retrospective single-centre study enrolled 168 adult Crohn’s disease patients treated for 1 year with infliximab originator or biosimilar. Assessment included achievement of clinical remission (during induction and maintenance therapy and follow-up period – 24 months) and occurrence of adverse events.ResultsForty-seven patients taking infliximab and 68 on biosimilar were anti-TNF-α naïve. There were no differences in clinical remission rate between naïve and non-naïve patients after 1 year of treatment (infliximab – 80.9% and 73.1%, respectively; biosimilar – 79.4% and 74.1%, respectively). The relapse rate during the follow-up period was higher in anti-TNF-α non-naïve patients (p < 0.001) with no significant differences between two groups. Adverse events were more common in anti-TNF-α non-naïve patients with no difference between infliximab and biosimilar groups (13.3% vs. 17.6%, respectively). The infliximab group of anti-TNF-α naïve patients had a higher rate of adverse events compared to the biosimilar (8.1% vs. 1.9%), but it did not reach statistical significance.ConclusionsThis is a study comparing anti-TNF-α naïve and non-naïve patients with Crohn’s disease. Relapse rate during follow-up was significantly higher in anti-TNF-α non-naïve patients, but with no significant differences between originator and biosimilar.

Predictors of Ustekinumab Failure in Crohn's Disease After Dose Intensification.

Many patients with Crohn's disease (CD) who lose response to the standard ustekinumab dose interval of every 8 weeks (q8w) undergo dose intensification to q4w or q6w. However, baseline factors that predict success or failure after dose intensification are unknown. We sought to identify predictors of failure of ustekinumab after dose intensification for patients with CD. This was a retrospective cohort study of adult CD patients undergoing ustekinumab dose intensification at a tertiary referral center between January 1, 2016, and January 31, 2019. Electronic health records were reviewed to obtain patient demographics, CD history, and laboratory data. The primary outcome was failure to achieve corticosteroid-free remission (Harvey-Bradshaw Index <5) within 12 months after intensification. The secondary outcome assessed was time to new biologic therapy after dose intensification. We used multivariable logistic regression and Cox regression to identify predictors of these outcomes. We included 123 patients who underwent ustekinumab dose intensification to q4w (n = 64), q5w (n = 1), q6w (n = 55), or q7w (n = 3). Multivariable logistic regression demonstrated that perianal disease, Harvey-Bradshaw Index, and opioid use at time of intensification were associated with failure to achieve remission. Cox regression demonstrated that perianal disease and corticosteroid use at time of intensification were associated with shorter time to a new biologic. Perianal disease, Harvey-Bradshaw Index, current opioid use, and current corticosteroid use are associated with ustekinumab failure after dose intensification in CD. Larger, prospective studies are needed to corroborate these findings and guide therapeutic strategies for patients who lose response to standard ustekinumab dosing.

Objectively assessed disease activity and drug persistence during ustekinumab treatment in a nationwide real-world Crohn's disease cohort.

ObjectiveLong-term evidence on ustekinumab treatment response and persistence in patients with Crohn’s disease in a real-world setting is scarce. We performed a retrospective nationwide chart review study of long-term clinical outcomes in Crohn’s disease patients treated with ustekinumab.MethodsThe study was conducted in 17 Finnish hospitals and included adult Crohn’s disease patients who received an initial intravenous dose of ustekinumab during 2017–2018. Disease activity data were collected at baseline, 16 weeks, and 1 year from health records.ResultsThe study included 155 patients. The disease was stricturing or penetrating in 69 and 59% had prior Crohn’s disease-related surgeries, and 97% had a treatment history of at least one biologic agent. Of 93 patients with ≥1 year of follow-up, 77 (83%) were still on ustekinumab at 1 year. In patients with data available, from baseline to the 1-year follow-up the simple endoscopic score for Crohn’s disease (SES-CD) decreased from 10 to 3 (P = 0.033), C-reactive protein from 7 to 5 mg/L, (P < 0.001) and faecal calprotectin from 776 to 305 μg/g (P < 0.001).ConclusionsUstekinumab treatment in patients with highly refractory Crohn’s disease resulted in high long-term treatment persistence and significantly reduced disease activity, assessed with objective markers for intestinal inflammatory activity.

Antibodies Against Glycoprotein 2 Are Specific Biomarkers for Pediatric Crohn's Disease.

Serological markers can assist in accurate differentiation between Crohn's disease (CD) and ulcerative colitis (UC). One such marker is anti-glycoprotein 2 (anti-GP2) which was shown to be a specific marker for CD in adult patients. The aim of our study was to assess the utility of anti-GP2 and GP2 as biomarkers for pediatric CD, and determine whether they correlate with disease activity. Serum samples were tested by ELISA for anti-GP2 isoform 4 IgG and IgA, and also for GP2. Results were correlated with demographic and clinical data. The cohort consisted of 53 pediatric patients with CD, 42 with UC, and 53 controls. Levels of anti-GP2 were significantly increased in pediatric patients with CD in comparison with patients with UC, and control subjects, with high positive predictive value for both IgG and IgA (97.9% and 82.6%, respectively). While specificity of anti-GP2 IgG and IgA was very high (98.7% and 90.0%, respectively), sensitivity was low (42.0% and 35.5% for IgG and IgA, respectively). In CD, anti-GP2 correlated with disease activity, and decreased in treatment-naïve patients following successful induction therapy. A higher IgA anti-GP2 was also demonstrated in patients with ileo-colonic involvement, and was associated with a younger age. Finally, positive GP2 level was identified in only 1/211 serum samples. A positive anti-GP2 level is highly associated with CD, while a negative result does not exclude CD. Additional studies are required to determine whether these markers can be used in pediatric patients with CD for risk stratification.

Systematic review: medical therapy for fibrostenosing Crohn's disease.

Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported. Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%-41.3%) and 18.5% (95% CI: 8.3%-36.2%), respectively over a median follow-up of 23months (range 5.5-105.8), and 21.8months (range 5-47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%-77.3%) over a median follow-up of 21.8months (range 5-47). There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery.

Prehabilitation: The Impact of Preoperative Exclusive Enteral Nutrition on Paediatric Patients With Crohn Disease.

Exclusive enteral nutrition (EEN) is effective in inducing remission in paediatric Crohn Disease (CD) and has been shown to reduce inflammation and improve outcomes in adult CD patients when used before resectional surgery. This retrospective study demonstrates that preoperative EEN is achievable in paediatric CD patients undergoing right hemicolectomy and is associated with positive peri-operative outcomes. Seventeen patients (8 who received preoperative EEN and 9 who did not) were included in the study. Six of 8 (75.0%) managed EEN orally; 1 via nasogastric tube and another via a previously sited gastrostomy. Use of preoperative EEN was associated with a decreased rate of moderate/severe disease on resection pathology (5/8 [62.5%] vs 9/9 [100%]; P = 0.04). Larger studies are required to determine the wider potential benefits of preoperative EEN on postoperative outcomes within paediatric practice.

Systematic review and meta-analysis: efficacy and safety of early biologic treatment in adult and paediatric patients with Crohn's disease.

There is an increasing body of evidence showing that earlier use of biologics improves clinical outcomes in Crohn's disease (CD). To perform a systematic review and meta-analysis to assess the impact of early biologic use in the treatment of CD. PubMed and Embase databases were searched for English language papers and conference abstracts published through April 30, 2019. Studies were selected for inclusion if patients initiated biologics within 2years of a CD diagnosis or if earlier biologics use (top-down) was compared with a conventional step-up strategy. Random-effects meta-analyses were conducted to compare clinical remission (CR), relapse and endoscopic healing rates between early biologic treatment (<2years of disease duration or top-down treatment strategy) and late/conventional treatment (biologic use after >2years of disease duration or conventional step-up treatment strategy). A total of 3069 records were identified, of which 47 references met the selection criteria for systematic review. A total of 18471 patients were studied, with a median follow-up of 64weeks (range 10-416). Meta-analysis found that early use of biologics was associated with higher rates of clinical remission (OR 2.10 [95% CI: 1.69-2.60], n=2763, P<.00001), lower relapse rates (OR 0.31 [95% CI: 0.14-0.68], n=596, P=.003) and higher mucosal healing rates (OR 2.37 [95% CI: 1.78-3.16], n=994, P<.00001) compared with late/conventional management. Early biologic treatment is associated with improved clinical outcomes in both adult and paediatric CD patients, not only in prospective clinical trials but also in real-world settings.

NOD2 Gene Status in Pediatric and Adult Crohn Disease Patients in Algerian Population

Background: Chronic Inflammatory Bowel Diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC) are gastrointestinal disorders under the influence of a complex genetic basis. One hundred sixty-three predisposition loci were identified by genome-wide association (GWAS) studies, refocusing the pathogenesis of IBD on immunity genes. The NOD2 gene has been widely implicated in the pathogenesis of IBD in different geographical populations. Three most common mutations within NOD2 gene were selected, namely SNP8, C/T (R702W variant), SNP12, G/C (G908R variant) and SNP13, (1007fsinsC variant). We investigated these three SNP in a pediatric Algerian cohort for the first time, since no previous association studies between pediatric IBD and the NOD2 gene were available for the Algerian population. Methods: A case-control study was performed in the pediatric IBD population. PCR-RFLP was used to detect the three NOD2 gene mutations in 46 CD patients and 100 healthy control subjects. All samples were genotyped for the NOD2 gene Polymorphisms by the PCR-RFLP method. Statistical study was performed by the Fisher exact test or Chi-2 using the GraphPad Prism 7.0 software. Then data from the pediatric cohort were compared to our precedent published data from a case-control study performed on a cohort including 132 IBD patients and 114 healthy control subjects. Results: In the pediatric cohort, there is no statistically differences in allelic frequencies between cases and controls respectively R702W (6.36% vs. 6.38%; p=1), G908R (2.72% vs. 1.06%; p=0.6) and 1007fsinsC mutation was found neither in the CD patients nor in control. In the adult cohort, the R702W allelic variant showed the highest frequency in CD patients (8%) (p = 0.09, OR = 3.67, 95%CI: 0.48-4.87) but its frequency was also high in controls (5%) (p = 0.4; OR = 1.4; 95%CI: 0.65-3.31). Likewise, G908R and 1007fsinsC mutations showed similar frequency in CD patients and in controls (3% vs. 2%; p= 0.5; OR=1.67; 95%CI: 0.44-6.34; 2% vs.1%; p=0.4, OR=2.69; 95%CI: 0.48-14.87, respectively). The total frequency of the mutated NOD2 chromosomes was higher in adult CD patients (13%) than in pediatric CD patients (9%). In our precedent study on the adult cohort, we have confirmed that the NOD2 gene is significantly associated with a specific clinical sub-phenotype in CD, indicating that the NOD2 gene is involved in IBD susceptibility across Algerian adult population. However, we failed to show any association between the three variants of the NOD2 gene across Algerian pediatric CD patients. Conclusion: In our precedent study, we have confirmed that the NOD2 gene is significantly associated with a specific clinical sub-phenotype in adult CD patients. Here, our results show no association of NOD2 gene variants with pediatric MC. The low penetrance of the at-risk genotypes we observed indicates that the NOD2 gene does not delineate a subgroup of simple Mendelian diseases.

655 Tumor Necrosis Factor Antagonists Are Superior to Ustekinumab and Vedolizumab for the Prevention of Postoperative Recurrence in Adult Crohn's Disease

INTRODUCTION: Relapse of Crohn's disease (CD) is common after surgical resection. Prior data have demonstrated that postoperative tumor necrosis factor antagonists (anti-TNF) may reduce recurrence, although little is known about the efficacy of other biologic therapies. The aim of this study was to compare biologics for preventing postoperative objective recurrence in adult CD patients. METHODS: We performed a retrospective chart review of CD patients who underwent intestinal resection from 2012 to 2018. Demographics, IBD history, pre- and postoperative course were obtained from the electronic medical record. The primary outcome was postoperative recurrence during follow up, defined as a composite of endoscopic (Rutgeerts grade &gt; i2), biochemical (increase in CRP &gt;5 mg/dL), or radiographic (presence of active inflammation) disease recurrence stratified by postoperative biologic exposure, including anti-TNF, vedolizumab (VDZ), ustekinumab (UST), and no therapy. Student's t-test, Pearson's chi-squared, logistic and Cox regression analyses were used to detect differences in the composite and components of the outcome among these groups. RESULTS: 123 patients were included. CD recurrence occurred in 36.6% of patients (13.0% biochemically, 24.4% endoscopically, 16.3% radiographically) at a median of 6.9 months (IQR 3.3-14.1) from surgery (Table 1). The number of patients in the anti-TNF, VDZ, UST, and no therapy groups were 57 (46.7%), 6 (4.9%), 13 (10.7%), and 46 (37.7%), respectively. Biologic therapy was initiated after ileostomy reversal within 3 months for 55 patients (72.4%), between 3-6 months for 11 patients (14.5%), and between 6-12 months for 10 patients (13.2%). Adjusting for prior resection and anti-TNF exposure, any biologic initiation within 6 months of surgery was superior to initiation after 6 months for preventing postoperative endoscopic recurrence (OR 0.24, 0.06-0.92), but not for the composite outcome. There were statistically significant differences among biologics for recurrence (Figure 1). Adjusting for prior resection and anti-TNF exposure, less patients relapsed under anti-TNF exposure compared to UST (HR 3.46, 1.45-8.23) for the composite outcome, and compared to UST (HR 3.95, 1.43-10.9) and VDZ (HR 4.42, 1.02-19.1) for endoscopic recurrence (Figure 2). CONCLUSION: Among CD patients, initiation of biologics within 6 months and anti-TNF agents were superior in preventing postoperative recurrence compared to other management strategies.

Assessment of bioelectrical phase angle as a predictor of nutritional status in patients with Crohn's disease: A cross sectional study

The assessment of body composition (BC) can be used to identify malnutrition in patients with Crohn's disease (CD). The aim of this study was to evaluate the nutritional status of CD patients by assessing BC, phase angle (PhA) and muscle strength. Differences in disease duration and medications were also considered. Consecutive adult CD patients aged 18-65 years were enrolled in this cross-sectional study. Disease activity was clinically defined by the Crohn's Disease Activity Index (CDAI) in the active and quiescent phases. All participants underwent anthropometry, BC and handgrip-strength (HGS) measurements; additionally, blood samples were taken. Data from CD patients were also compared with age-, sex- and BMI-matched healthy people. A total of 140 CD patients with a mean age of 38.8±13.9 years and a mean body weight of 64.9±12kg were recruited and compared to controls. The findings showed that all nutritional parameters, especially PhA and HGS, were lower in CD patients than in controls, and these parameters were substantially impaired as disease activity increased. Active CD patients had a lower body weight and fat mass than both the quiescent and control groups. PhA was negatively correlated with age (r=-0.362; p=0.000) and CDAI (r=-0.135; p=0.001) but was positively associated with fat free mass (FFM) (r=0.443; p=0.000) and HGS (r=0.539; p=0.000). Similarly, serum protein markers were lower in the active CD group than in the quiescent group (p<0.05). Disease duration and medications did not significantly affect nutritional status. BIA-derived PhA is a valid indicator of nutritional status in CD patients, and its values decreased with increasing disease activity. Additionally, small alterations in BC, such as low FFM, and reduced HGS values can be considered markers of nutritional deficiency. Therefore, the assessment of BC should be recommended in clinical practice for screening and monitoring the nutritional status of CD patients.

Decreasing Trends in Intestinal Resection and Re-Resection in Crohn's Disease: A Nationwide Cohort Study.

To assess time trends in intestinal resection and re-resection in Crohn's disease (CD) patients. CD treatment has changed considerably over the past decades. The effect of these advances on the necessity of intestinal resections and the risk of re-resection is unclear. In this nationwide cohort study, adult CD patients with ileocolonic, small bowel, colon, or rectum resections between 1991 and 2015 were included. Data were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology (PALGA). Time trends were analyzed with a broken stick model and Cox proportional hazard model with smoothing splines. The identified cohort comprised 8172 CD patients (3293/4879 male/female) in whom 10,315 intestinal resections were performed. The annual intestinal resection rate decreased nonlinearly from 1.9/100,000 (1991) to 0.2/100,000 (2015). A significantly steeper-decrease was observed before 1999 (slope –0.13) as compared to subsequent years (slope –0.03) (p<0.001). Analogous trends were observed for ileocolonic, small bowel, and colon resections. Overall cumulative risk of re-resection was 10.9% at 5 years, 18.6% at 10 years, and 28.3% at 20 years after intestinal resection. The hazard for intestinal re-resection showed a nonlinear decreasing trend, with hazard ratio 0.39 (95% confidence interval 0.36-0.44) in 2000 and hazard ratio 0.25 (95% confidence interval 0.18-0.34) in 2015 as compared to 1991. Over the past 25 years, intestinal resection rate has decreased significantly for ileocolonic, small bowel, and colonic CD. In addition, current postoperative CD patients are at 75% lower risk of intestinal re-resection.

Perioperative management and early complications after intestinal resection with ileocolonic anastomosis in Crohn's disease: analysis from the PRACTICROHN study.

BackgroundThis study is aimed at describing the prevalence of and risk factors associated with early post-operative complications after Crohn’s disease-related intestinal resection.MethodsThis was a retrospective analysis of data from the PRACTICROHN cohort. Adult Crohn’s disease patients who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010 were included. The complications evaluated included death, ileus, anastomotic leak, abscess, wound infection, catheter-related infection, digestive bleeding and other extra-abdominal infections that occurred in the 30 days after surgery.ResultsA total of 364 patients (median age at surgery 38 years and 50% men) were included. Indication for surgery was: stricturing disease (46.4%), penetrating disease (31.3%), penetrating and stricturing disease (14.0%) or resistance to medical treatment (5.8%). Early complications were recorded in 100 (27.5%) patients, with wound infection, intra-abdominal abscess and anastomotic leakage being the most frequent complications. Median hospitalization duration was 16 days for patients with complications vs. 9 days without complications (P < 0.001). Complications were more common among patients with penetrating disease (36/114, 31.6%) and those refractory to treatment (9/21, 42.9%) compared with stricturing disease (45/169, 26.6%) or stricturing + penetrating disease (6/51, 11.8%) (P = 0.040). The rate of complications was higher among patients with diagnosis made at the time of surgery (15/31, 48.4%) compared with the rest (85/331, 25.7%) (P = 0.013). Medication received at the time of surgery did not affect the rate of complications.ConclusionsAlmost a quarter of patients developed early complications after intestinal resection. Penetrating disease and urgent surgery were associated with an increased risk of complications.

Systematic review: outcomes and adverse events from randomised trials in Crohn's disease.

SummaryBackgroundThe suitability of disease activity indices has been challenged, with growing interest in objective measures of inflammation.AimTo undertake a systematic review of efficacy and safety outcomes in placebo‐controlled randomised controlled trials (RCTs) of patients with Crohn's disease.MethodsMEDLINE, EMBASE, CINAHL and Cochrane Library were searched until November 2015, for RCTs of adult Crohn's disease patients treated with medical or surgical therapies. Data on efficacy and safety outcomes, end‐point definitions, and measurement instruments were extracted and stratified by publication date (pre‐2009 and 2009 onwards).ResultsOne hundred and eighty‐one RCTs (110 induction and 71 maintenance) were identified, including 23 850 patients. About 92.3% reported clinical efficacy endpoints. The Crohn's Disease Activity Index (CDAI) dominated, defining clinical response or remission in 63.5% of trials (35 definitions of response or remission). CDAI < 150 was the commonest endpoint, but reporting reduced between periods (46.4%‐41.1%), whilst use of CDAI100 increased (16.8%‐30.4%). Fistula studies most commonly reported fistula closure (9, 90.0%). Reporting of biomarker, endoscopy and histology endpoints increased overall (33.3%‐40.6%, 14.4%‐30.4% and 3.2%‐12.5%, respectively), but were heterogeneous and rarely reported in fistula trials. Patient‐reported outcome measures were reported in 41.4% of trials and safety endpoints in 35.4%. Many of the common adverse events relate to disease exacerbation or treatment failure.ConclusionsTrial endpoints vary across studies, over time and are distinct in fistula studies. Despite growth in reporting of objective measures of inflammation and in patient‐reported outcome measures, there is a lack of standardisation. This confirms the need for a core outcome set for comparative effectiveness research 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.

MRI reveals different Crohn's disease phenotypes in children and adults.

To identify differences between two cohorts of adult and pediatric patients affected by Crohn's disease (CD), with regard to lesion location in the small intestine and colon-rectum, lesion activity, and prevalence of perianal disease (PD), using MRI as the main diagnostic tool. We retrospectively reviewed 350 consecutive MRI examinations performed between 2013 and 2016 in outpatients or inpatients with histologically proven CD, monitored by the Gastroenterology and Pediatric Units of our Hospital. The magnetic resonance enterography (MRE) protocol for adult and pediatric CD patients routinely includes evaluation of nine different intestinal segments (from jejunum to rectum) and of the anal canal. Intestinal activity was also calculated using a validated score. Perianal disease (PD) was staged. Fisher's exact test was used and the odds ratio (OR) was calculated. Two hundred and nineteen out of 350 MRI studies (118 adults and 101 children) were included. The prevalence of PD was 34.6% in children and 16.1% in adults (OR = 2.8; p = 0.0017). Pediatric patients showed more frequent rectal involvement (29.7% vs 13.5%, OR = 2.7; p = 0.0045) and higher risk of PD in the presence of rectal disease (p = 0.043; OR = 4.5). In pediatric patients with severe colorectal disease, the prevalence of PD was twofold (86.7% vs 40%; p = 0.072). Using the clinical Montreal classification for lesion location, no significant differences emerged between the two patient populations. MRI showed a significantly higher prevalence of rectal involvement and perianal disease in the pediatric population. These results may have a relevant clinical impact and deserve further investigation. • To our knowledge, this is the largest morphological comparative study available in the literature using MRI as the main diagnostic tool to compare adult patients and children with Crohn's disease. • Our study showed significant differences between adults and children: a higher prevalence of rectal and perianal fistulous disease (PD) in pediatric patients and an increased prevalence of PD in the presence of severe colon-rectum involvement. • The association of rectal and perianal disease implies a poorer clinical prognosis and a higher risk of disabling complications in pediatric patients.

Enteral nutrition and dietary modification in adult and paediatric Crohn's disease: a systematic review

Background: Crohn's disease (CD) is an inflammatory bowel disease (IBD) that causes exacerbations of inflammation in the gastrointestinal tract, with secondary symptoms including malnutrition and weight loss. Its aetiology is related to genetics, the intestinal microbiome and environmental factors, and treatment aims to manage symptoms and induce remission. Aims: This systematic literature review considers the evidence for common dietary modifications and nutritional support for both adult and paediatric CD patients. Methods: PubMed and Google Scholar were searched for randomised control trials or others relating to diet and nutritional interventions in CD patients. Results: Eight articles were selected that met inclusion criteria. There was some limited evidence for the use in adults of low-FODMAP, gluten-free, IgG4-guided exclusion, low-residue, paleo and specific-carbohydrate diets. Only the specific-carbohydrate diet was studied in children. Partial and exclusive enteral nutrition were effective interventions in both populations, though more commonly used in children. Conclusion: In paediatric patients, enteral nutrition is the preferred treatment for severe CD. In adult CD, IgG4-exclusion diets are particularly likely to help induce remission. More research is needed before any conclusive recommendations can be made.

Loss of response to scheduled infliximab therapy for Crohn's disease in adults: A systematic review and meta-analysis.

To determine the potential predictors of loss of response (LOR) to infliximab (IFX) maintenance therapy for adult patients with Crohn's disease (CD). We searched for English-language articles published between 1990 and March 2017 in PubMed, Embase, and the Cochrane Library. After identifying eligible studies, data extraction was performed independently by two reviewers. The potential prognostic variables were identified and dichotomized for meta-analysis. Based on the heterogeneity among study variables, random-effects models was used in our meta-analysis. Twenty-six studies met our eligibility criteria and consolidated drug response data were obtained from 3212 patients. The pooled rate of LOR to IFX maintenance therapy with a median follow-up of 1.1 years was 34%. The incidence of LOR to IFX therapy was increased in CD patients with perianal lesions (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.04-2.75, P = 0.03), colon involvement (OR 2.56, 95% CI 1.20-5.50, P = 0.02) and younger age at CD onset (standardized mean difference -0.79, 95% CI -1.41 to -0.18, P = 0.01). The meta-analysis estimates the incidence of LOR among adult CD patients undergoing IFX therapy is 34%. The presence of perianal lesions, younger age at CD onset, and involvement of the colon are relative risk factors of LOR in CD patients received scheduled IFX maintenance therapy.