Viscoelastic properties of small bowel mesentery at MR elastography in Crohn's disease: a prospective cross-sectional exploratory study.

BACKGROUND: Creeping fat is a pathological feature of small bowel Crohn's disease (CD), with literature suggesting that bowel resection with extended mesenteric resection is related to less postoperative recurrences. Conventional imaging is unable to accurately quantify the disease involvement (i.e., fibrosis) of creeping fat. Quantification of disease involvement could be useful in decision-making for additional extended mesenteric resection. We investigated the feasibility of magnetic resonance elastography (MRE) of the mesentery and if MRE is capable to detect fibrotic disease involvement of mesentery in active CD. METHODS: Multifrequency MRE yielded spatial stiffness (shear wave speed, SWS, |G*|) and fluidity maps (φ). Viscoelastic properties of seven CD patients' mesentery were compared to age- and sex-matched healthy volunteers (HV) (Mann-Whitney U-test). Within CD patients, the affected and "presumably" unaffected mesentery were compared (Wilcoxon-signed rank test). Repeatability was tested in 15 HVs (Bland-Altman analysis, coefficient of variation [CoV]). Spearman rank correlations were used to investigate the relation between microscopically scored amount of mesenteric fibrosis and viscoelastic parameters. RESULTS: SWS, |G*|, and φ of affected mesentery in CD were higher compared to HV (p = 0.017, p = 0.001, p = 0.017). Strong correlations were found between percentage of area of mesenteric fibrosis and SWS and |G*| (p < 0.010). No differences were found within CD between affected and presumably unaffected mesentery. Repeatability of SWS showed 95% limits of agreement of (-0.09, 0.13 m/s) and within-subject CoV of 5.3%. CONCLUSION: MRE may have the potential to measure fibrotic disease involvement of the mesentery in CD, possibly guiding clinical decision-making with respect to extended mesenteric resection. TRIAL REGISTRATION: Dutch trial register, NL9105 , registered 7 December 2020. RELEVANCE STATEMENT: MRE may have the potential to measure the amount of mesenteric fibrosis of the affected mesenteric fat in active Crohn's disease, giving more insight into disease progression and could potentially play a role in clinical decision-making for extended mesenteric resection. KEY POINTS: • MRE of the mesentery in patients with active CD is feasible. • Fluidity and stiffness of the mesentery increase in active CD, while stiffness correlates with the histopathological amount of mesenteric fibrosis. • MRE provides biomarkers to quantify mesenteric disease activity in active CD.

Quality of care indicators in inflammatory bowel disease in a tertiary referral center with open access and objective assessment policies.

BACKGROUND: In the management of inflammatory bowel diseases, there is considerable variation in quality of care. AIMS: The aim of this study was to evaluate structural, access/process components and outcome quality indicators in our tertiary referral IBD center. METHODS: In the first phase, structural/process components were assessed, followed by the second phase of formal evaluation of access and management on a set of consecutive IBD patients with and without active disease (248CD/125UC patients, median age 35/39 years). RESULTS: Structural/process components of our IBD center met the international recommendations. At or around the time of diagnosis usual procedures were full colonoscopy in all patients, with ileocolonoscopy/gastroscopy/CT/MRI in 81.8/45.5/66.1/49.6% of CD patients. A total of 86.7% of CD patients had any follow-up imaging evaluation or endoscopy. The median waiting time for non-emergency endoscopy/CT/MRI was 16/14/22 days. During the observational period patients with flares (CD/UC:50.6/54.6%) were seen by specialist at the IBD clinic within a median of 1day with same day laboratory assessment, abdominal US, CT scan/surgical consult and change in therapy if needed. Surgery and hospitalization rates were 20.1/1.4% and 17.3/3.2% of CD/UC patients. CONCLUSION: Our results highlight that structural components and processes applied in our center are in line with international recommendations, including an open clinic concept and fast track access to specialist consultation, endoscopy and imaging.

Prediction of Short- and Medium-term Efficacy of Biosimilar Infliximab Therapy. Do Trough Levels and Antidrug Antibody Levels or Clinical And Biochemical Markers Play the More Important Role?

BACKGROUND AND AIMS: Biosimilar infliximab CT-P13 received European Medicines Agency [EMA] approval in June 2013 for all indications of the originator product. In the present study, we aimed to evaluate the predictors of short- and medium-term clinical outcome in patients treated with the biosimilar infliximab at the participating inflammatory bowel disease [IBD] centres in Hungary. METHODS: Demographic data were collected and a harmonised monitoring strategy was applied. Clinical and biochemical activities were evaluated at Weeks 14, 30, and 54. Trough level [TL] and anti-drug antibody [ADA] concentrations were measured by enzyme-linked immunosorbent assay [ELISA] [LT-005, Theradiag, France] at baseline at 14, 30 and 54 weeks and in two centres at Weeks 2 and 6. RESULTS: A total of 291 consecutive IBD patients (184 Crohn's disease [CD] and 107 ulcerative colitis [UC]) were included. In UC, TLs at Week 2 predicted both clinical response and remission at Weeks 14 and 30 (clinical response/remission at Week 14: area under the curve [AUC] = 0.81, p < 0.001, cut-off: 11.5 µg/ml/AUC = 0.79, p < 0.001, cut-off: 15.3µg/ml; clinical response/remission at Week 30: AUC = 0.79, p = 0.002, cut-off: 11.5 µg/ml/AUC = 0.74, p = 0.006, cut-off: 14.5 µg/ml), whereas ADA positivity at Week 14 was inversely associated with clinical response at Week 30 [58.3% vs 84.8% ,p = 0.04]. Previous anti-tumour necrosis factor [TNF] exposure was inversely associated with short-term clinical remission [Week 2: 18.8% vs 47.8%, p = 0.03, at Week 6: 38.9% vs 69.7%, p = 0.013, at Week 14: 37.5% vs 2.5%, p = 0.06]. In CD, TLs at Week 2 predicted short-term [Week 14 response/remission, AUCTLweek2 = 0.715-0.721, p = 0.05/0.005] but not medium-term clinical efficacy. In addition, early ADA status by Week 14 [p = 0.04-0.05 for Weeks 14 and 30], early clinical response [p < 0.001 for Weeks 30/54] and normal C-reactive protein [CRP] at Week 14 [p = 0.005-0.0001] and previous anti-TNF exposure [p = 0.03-0.0001 for Weeks 14, 30, and 54] were associated with short-and medium-term clinical response and remission. CONCLUSIONS: In UC, early TLs were predictive for short- and medium-term clinical efficacy, whereas in CD, Week 2 TLs were associated only with short-term clinical outcomes.

Optimizing biological therapy in Crohn's disease.

Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn's disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn's disease and identify strategies to optimize biological treatment.

Tuberculin Skin Test and Quantiferon in BCG Vaccinated, Immunosuppressed Patients with Moderate-to-Severe Inflammatory Bowel Disease.

BACKGROUND AND AIMS: There are few data available on the effect of immunomodulator/biological therapy on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in BCG-vaccinated immunosuppressed patients with inflammatory bowel disease (IBD). Our aim was to define the accuracy, predictors and agreement of TST and IGRA in a BCG-vaccinated immunosuppressed referral IBD cohort. METHODS: 166 consecutive moderate-to-severe IBD patients (122 Crohn's disease, CD and 44 ulcerative colitis, UC) were enrolled in a prospective study from three centers. Patients were treated with immunosuppressives and/or biologicals. IGRA and TST were performed on the same day. Both in- and outpatient records were collected and comprehensively reviewed. RESULTS: TST positivity rate was 23.5%, 21.1%,14.5% and 13.9% when cut-off values of 5, 10, 15 and 20mm were used. IGRA positivity rate was 8.4% with indeterminate result in 0.6%. Chest X-ray was suggestive of latent tuberculosis in 2 patients. Correlation between TST and IGRA was moderate (kappa: 0.39-0.41, p<0.001). In addition, a cut-off of 14 and 17mm for TST was defined to identify IGRA positivity in a ROC analysis (AUC: 0.76, p=0.03). TST and/or IGRA positivity was not influenced by medical therapy or disease phenotype. Importantly, smoking was identified as a risk factor for TST but not IGRA positivity (OR: 2.70-5.02, p<0.01, for TSTcut-offs=5-20mm). CONCLUSION: TST and IGRA tests are partly complimentary methods, and additional testing by TST (with a cut-off of >15mm) should be considered to identify patients at risk for latent TB. Accuracy is satisfactory in BCG-vaccinated, immunosuppressed IBD patients. Smoking is a risk factor for TST positivity.

Low incidence of venous thromboembolism in inflammatory bowel diseases: prevalence and predictors from a population-based inception cohort.

OBJECTIVE: Patients with inflammatory bowel diseases (IBD) are considered to have an increased risk for venous thromboembolism (VTE). The aim of the present study was to analyze the incidence and risk factors of VTE in a population-based inception cohort in the Veszprem province database between 1977 and 2012. MATERIAL AND METHODS: A total of 1708 incepted IBD patients were included (male/female: 879/829; CD (Crohn's disease): 648, age at onset: 29, interquartile range (IQR): 22-39; UC (ulcerative colitis): 1060, age at onset: 36, IQR: 26-50 years). Both in- and outpatient records were collected and comprehensively reviewed and followed up for a total of 21,369 patient-years. RESULTS: Twenty-two VTE events were identified in 19 patients (6 events in 5 CD and 16 in 14 UC patients). The incidence rate of VTE in IBD was 1.03 per 1000 patient-years. The risk of VTE in UC was associated with extensive location (odds ratio (OR): 3.25, 95% confidence interval (CI): 1.13-9.35), presence of fulminant episode during the disease course (OR: 4.15, 95% CI: 1.28-13.5), smoking (OR: 3.46, 95% CI: 1.14-10.5), and need for steroids (OR: 2.97, 95% CI: 0.99-8.92). CONCLUSION: The incidence of VTE was lower than previously reported. The incidence was higher in males and in UC it was associated with extensive disease, fulminant episodes, corticosteroids-requiring disease and smoking, but not with age at onset.