Isolated ileal blind loop inflammation after intestinal resection with ileocolonic anastomosis in Crohn's disease: an often neglected endoscopic finding with an unfavorable outcome

OBJECTIVE: Postoperative endoscopic recurrence in patients with Crohn's disease (CD) is commonly classified using the Rutgeerts score. Ulcerations in the ileal blind loop are not taken into account in the Rutgeerts score, and the clinical relevance of these lesions is unknown. This study aimed to assess the outcome of isolated ileal blind loop inflammation (IBLI) in postoperative CD patients. METHODS: Adult CD patients who underwent intestinal surgery with ileocolonic anastomosis between 1997 and 2017 were included and postoperative endoscopy reports were retrospectively reviewed. IBLI was defined as isolated inflammation of the ileal blind loop with or without ulcera confined to the anastomosis. Outcome was assessed using endoscopic recurrence (Rutgeerts >i2) and surgical recurrence (re-resection). RESULTS: A total of 341 CD patients were included. In 125 out of 341 (37%) patients, the ileal blind loop was described in the endoscopy reports. IBLI was reported in 43 of 341 (13%) patients. Start or step-up drug therapy was initiated in 10 of 32 (31%) IBLI patients with abdominal symptoms within a median of 0.9 months [interquartile range (IQR) 0.7-1.4] after ileocolonoscopy. Endoscopic recurrence occurred in 4 out of 38 (11%) IBLI patients without re-resection, within a median of 12.4 months (IQR 6.8-13.3). Intestinal re-res

Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab- and ustekinumab-treated patients with inflammatory bowel disease-a prospective multicentre cohort study

Background: Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD). Aims: To evaluate the association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD. Methods: IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid-free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders. Results: We included 203 vedolizumab- and 207 ustekinumab-treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9-104.0) and 48.4 (IQR 24.4-55.1) weeks, median follow-up time 104.0 (IQR 103.1-104.0) and 52.0 weeks (IQR 49.3-100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022-1.883, P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127-2.231, P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034-2.541, P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes. Conclusions: Comorbidity - but not age - is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients

Vedolizumab for Inflammatory Bowel Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, A Nationwide Prospective Observational Cohort Study: ICC Registry – Vedolizumab

Prospective data of vedolizumab treatment for patients with inflammatory bowel disease (IBD) beyond 1 year of treatment is scarce but needed for clinical decision making. We prospectively enrolled 310 patients with IBD (191 with Crohn's disease (CD) and 119 patients with ulcerative colitis (UC)) with a follow-up period of 104 weeks (interquartile range: 103–104) in a nationwide registry. The corticosteroid-free clinical remission rate (Harvey Bradshaw Index ≤ 4, Short Clinical Colitis Activity index ≤ 2) at weeks 52 and 104 were 28% and 19% for CD and 27% and 28% for UC, respectively. Fifty-nine percent maintained corticosteroid-free clinical remission between weeks 52 and 104. Vedolizumab with concomitant immunosuppression showed comparable effectiveness outcomes compared with vedolizumab monotherapy (week 104: 21% vs. 23%; P = 0.77), whereas 8 of 13 severe infections occurred in patients treated with concomitant immunosuppression. To conclude, the clinical effect was 19% for CD and 28% for UC after 2 years of follow-up regardless of concomitant immunosuppression

Tofacitinib for ulcerative colitis:results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Background: Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). Aim: To evaluate effectiveness, safety and use of tofacitinib in daily practice. Methods: UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation. Results: In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively. Conclusion: Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients

High Percentage of IBD Patients with Indefinite Fecal Calprotectin Levels: Additional Value of a Combination Score

BACKGROUND AND AIM: Monitoring mucosal inflammation in inflammatory bowel disease (IBD) is of major importance to prevent complications and improve long-term disease outcome. The correlation of clinical activity indices with endoscopic disease activity is, however, moderate. Fecal calprotectin (FC) is a better predictor of mucosal inflammation, but values between 100 and 250 µg/g are difficult to interpret in clinical practice. We aimed to evaluate the occurrence of indefinite FC levels in a real-life IBD cohort and study the additional value of a combination of biochemical markers and clinical activity indices. METHODS: In total, 148 Crohn’s disease (CD) and 80 ulcerative colitis (UC) patients visiting the outpatient clinic were enrolled. FC, clinical disease activity scored by the Harvey–Bradshaw index or Simple Clinical Colitis Activity Index, and C-reactive protein (CRP) were assessed. In a subset of patients, endoscopic activity was scored by the simple endoscopic score-Crohn’s disease and Mayo endoscopic subscore. Clinical activity index, CRP, and FC were integrated in a combination score and compared with endoscopy. RESULTS: Indefinite FC values were present in 24% of CD and 15% of UC. In the cohort of patients with endoscopy scores available, the combination score predicted endoscopic disease activity in CD with a sensitivity of 83% and specificity of 69% [positive predictive value (PPV) 58%, negative predictive value (NPV) 89%]. In UC, this was 88 and 75% (PPV 93%, NPV 60%). CONCLUSIONS: A combination of FC with clinical activity indices or CRP may aid in classifying patients with indefinite disease activity according to FC alone

Faecal Microbiota Dynamics and their Relation to Disease Course in Crohn's Disease

BACKGROUND: Microbial shifts have been associated with disease activity in Crohn's disease [CD], but findings on specific taxa are inconsistent. This may be due to differences in applied methods and cross-sectional study designs. We prospectively examined the faecal microbiota in adult CD patients with changing or stable disease course over time. METHODS: Faeces were collected at two time-points from 15 healthy control individuals [HCs], 35 CD patients who were in remission and who maintained remission [RRs], and 22 CD patients during remission and also during subsequent exacerbation [RAs]. The microbial composition was assessed by 16S rRNA [V4] gene sequencing. RESULTS: Compared with HCs, patients with CD had a lower microbial richness [p = 0.0002] and diversity [p = 0.005]. Moreover, the microbial community structure of a subset of patients, clustered apart from HCs, was characterized by low microbial diversity and Faecalibacterium abundance. Patients within this cluster did not differ with respect to long-term disease course compared with patients with a 'healthy-appearing' microbiota.Over time, microbial richness and diversity did not change in RR versus RA patients. Although the microbial community structure of both RR and RA patients was less stable over time compared with that of HCs, no differences were observed between the patient groups [p = 0.17]; nor was the stability impacted by Montreal classification, medication use, or surgery. CONCLUSION: The altered microbiota composition and stability in CD was neither associated with disease activity nor long-term disease course, questioning its involvement in the development of an exacerbation. The aberrant microbiota composition in a subset of CD patients warrants further exploration of a more microbiota-driven etiology in this group

Volatile metabolites in breath strongly correlate with gut microbiome in CD patients

Microbiota composition and its metabolic capacity are very important for host health. Evidence suggests that gut microbiome is involved in the metabolites production by host-microbiome interaction. These metabolites can be absorbed in blood and excreted in exhaled air. Although, profiles of gut microbiota and exhaled metabolites were associated with gastrointestinal diseases, a direct link between them has not yet been investigated. The aim of the study was to investigate the relation between volatiles in breath and gut microbiome in active and quiescent Crohn's disease (CD) via a multivariate statistical approach. Canonical correlation analysis (CCA) was used to assess the relation between exhaled metabolites and faecal bacterial species.From 68 CD patients, 184 repeated faecal and breath samples were collected (92 active and 92 quiescent disease). The microbiota composition was assessed by the pyrosequencing of the 16 S rRNA V1-V3 gene region and breath metabolites by gas chromatography mass spectrometry.In active disease, CCA analysis identified 18 metabolites significantly correlated with 19 faecal bacterial taxa (R = 0.91 p-value 3.5*10-4). In quiescent disease 17 volatile metabolites were correlated with 17 bacterial taxa (R = 0.96 p-value 2.8*10-4). Nine metabolites and three bacteria taxa overlapped in active and inactive CD. This is the first study that shows a significant relation between gut microbiome and exhaled metabolites, and was found to differ between active and quiescent CD, indicating various underlying mechanisms. Unravelling this link is essential to increase our understanding on the functional effects of the microbiome and may provide new leads for microbiome-targeted intervention. (C) 2018 Elsevier B.V. All rights reserved.</p