COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. OBJECTIVE: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. METHODS: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. RESULTS: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. CONCLUSION: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

Higher adalimumab maintenance regimen is more effective than standard dose in anti-TNF experienced Crohn's disease patients.

BACKGROUND: Many Crohn's disease patients treated with anti-tumor necrosis factor (TNF) therapies suffer from loss of response over time and require dose escalation. The aim of this study was to evaluate the efficacy and safety of treating anti-TNF experienced Crohn's disease patients with higher maintenance regimens of adalimumab. METHODS: In a retrospective observational study, Crohn's disease patients receiving adalimumab were categorized according to their maintenance regimen; 40 mg weekly, 80 mg every other week or greater were defined as a high-dose maintenance regimen and 40 mg every other week was defined as a standard maintenance regimen. The primary outcome was time to treatment failure. RESULTS: Thirty-nine patients were started on high-dose regimens following induction and 40 patients received the standard regimen. According to a Kaplan-Meier survival curve analysis, time to treatment failure was significantly longer in patients in the high-dose group (P = 0.0015). Patients on high-dose adalimumab had a lower treatment failure rate (hazard ratio 0.21; P = 0.0005) when compared to patients on the standard regimen, after adjusting for induction dose and concomitant immunomodulator use. No difference in adverse events was identified between the groups (31 vs. 30%; P = 0.94). CONCLUSION: High-dose maintenance regimens were more effective than the standard adalimumab maintenance protocol with better short and long-term clinical outcomes.

Inflammatory bowel disease patient profiles are related to specific information needs: A nationwide survey.

BACKGROUND: Inflammatory bowel diseases (IBD) is a heterogenous, lifelong disease, with an unpredictable and potentially progressive course, that may impose negative psychosocial impact on patients. While informed patients with chronic illness have improved adherence and outcomes, previous research showed that the majority of IBD patients receive insufficient information regarding their disease. The large heterogeneity of IBD and the wide range of information topics makes a one-size fits all knowledge resource overwhelming and cumbersome. We hypothesized that different patient profiles may have different and specific information needs, the identification of which will allow building personalized computer-based information resources in the future. AIM: To evaluate the scope of disease-related knowledge among IBD patients and determine whether different patient profiles drive unique information needs. METHODS: We conducted a nationwide survey addressing hospital-based IBD clinics. A Total of 571 patients completed a 28-item questionnaire, rating the amount of information received at time of diagnosis and the importance of information, as perceived by participants, for a newly diagnosed patient, and for the participants themselves, at current time. We performed an exploratory factor analysis of the crude responses aiming to create a number of representative knowledge domains (factors), and analyzed the responses of a set of 15 real-life patient profiles generated by the study team. RESULTS: Participants gave low ratings for the amount of information received at disease onset (averaging 0.9/5) and high ratings for importance, both for the newly diagnosed patients (mean 4.2/5) and for the participants themselves at current time (mean 3.5/5). Factor analysis grouped responses into six information-domains. The responses of selected profiles, compared with the rest of the participants, yielded significant associations (defined as a difference in rating of > 0.5 points with a P < 0.05). Patients with active disease showed a higher interest in work-disability, stress-coping, and therapy-complications. Patients newly diagnosed at age > 50, and patients with long-standing disease (> 10 years) showed less interest in work-disability. Patients in remission with mesalamine or no therapy showed less interest in all domains except for nutrition and long-term complications. CONCLUSION: We demonstrate unmet patient information needs. Analysis of various patient profiles revealed associations with specific information topics, paving the way for building patient-tailored information resources.

Associations between quantitative evaluation of bowel wall microvascular flow by contrast-enhanced ultrasound and indices of disease activity in Crohn's disease patients using both bolus and infusion techniques.

PURPOSE: The aim is to investigate whether baseline contrast-enhanced ultrasound (CEUS) correlates with indices of activity in Crohn's disease (CD) and can predict response to medical treatment. METHODS: In this prospective study, symptomatic CD patients underwent baseline CEUS performed with Definity using both bolus and infusion methods. Time-intensity curves (TIC), peak intensity (PI), and area under curve (AUC) from a region of interest over the diseased bowel were calculated for both bolus and infusion acquisitions. We used Mann-Whitney U test for continuous and chi-square/two-tailed Fisher's exact test for categorical variable comparison and Spearman's correlation coefficient to correlate clinical score and CEUS kinetic parameters. RESULTS: Twenty-one patients (9 men, 12 women, median age 32 years) were accrued. Fifteen patients had clinically active disease defined as Harvey-Bradshaw Index (HBI) score ≥5. Median values of baseline CEUS parameters PI (bolus: 26 vs 8.86; P = .023 and perfusion: 7.6 vs 3.2; P = .009) and AUC (bolus: 769 vs 248.8; P = .036 and perfusion: 188.9 vs 73.9; P = .012) differed significantly in patients with active vs inactive disease. Nine patients with active disease underwent escalated or new treatment. Five were nonresponders. Responders had higher median values of baseline parameters (PI, bolus: 35 vs 18.8; P = .556, and perfusion: 7.6 vs 3.9; P = 190), (AUC, bolus: 1473.9 vs 314; P = .111, and perfusion: 154.7 vs 74.4, P = .286). CONCLUSIONS: CEUS kinetic parameters correlate with clinical and laboratory indices and are significantly higher in patients with active disease. The responders had higher CEUS kinetic parameters than nonresponders that did not reach statistical significance in our small cohort.

Correlation of 18F-FDG PET/MRE Metrics with Inflammatory Biomarkers in Patients with Crohn's Disease: A Pilot Study.

Background: To investigate the association between 18F-FDG (Fluorodeoxyglucose) PET (positron emission tomography)/MRE (magnetic resonance enterography) metrics with the inflammatory biomarkers fecal calprotectin and C-reactive protein (CRP) in patients with Crohn's disease (CD). Methods: This prospective pilot study was institutional review board (IRB) approved with informed consent obtained. Consecutive CD patients were referred to 18F-FDG PET/MRE. Patients in whom colonoscopy was performed and CRP and fecal calprotectin levels were measured were included. CRP and fecal calprotectin were regarded as positive for inflammation if they were greater than 0.5 mg/dl and 150 mcg/g, respectively. Correlation of quantitative variables was performed using the Pearson's correlation coefficient. Receiver operating characteristic (ROC) curves were drawn and the area under the curve (AUC) was calculated to evaluate the accuracy of PET and MRE metrics in determining the presence of inflammation evaluated by calprotectin and CRP levels. Results: Analysis of 21 patients (16 women and 5 men, 43 ± 18 years) was performed. Magnetic resonance index of activity (MaRIA) score had an AUC of 0.63 associated with fecal calprotectin and CRP. Adding apparent diffusion coefficient (ADC) and metabolic inflammatory volume (MIV) to MaRIA score resulted in an AUC of 0.92 with a cutoff value of 447 resulting in 83% and 100% sensitivity and specificity, respectively. Conclusion: The addition of ADC and MIV to the MaRIA score increases the accuracy for discrimination of disease activity in patients with CD. Trial registration number is 2015062.

Quality of life and uncertainty in Crohn's disease.

INTRODUCTION: Crohn's disease impairs patients' perception of health and has a negative impact on health-related quality of life. Although it is apparent that uncertainty is a significant factor that decreases quality of life, it has never been studied in patients with Crohn's disease. The objective of the present study was to examine the association between level of certainty, self-epistemic authority, Internet information gathering habits, and health-related quality of life. METHODS: A cross-sectional study of 105 Crohn's disease patients was conducted. Data were collected using a questionnaire composed of five parts: (1) demographic and clinical information; (2) health-related quality of life; (3) level of certainty; (4) self-epistemic authority; and (5) Internet information gathering habits regarding Crohn's disease. RESULTS: A significant positive correlation was demonstrated between levels of certainty and health-related quality of life. Self-epistemic authority correlated positively with certainty, while information gathering via the Internet was related to decreased certainty. Multiple regression analysis for factors associated with health-related quality of life showed a positive association with the level of certainty, while negative associations were found between Internet information seeking and disease activity with the quality of life. CONCLUSION: Level of certainty proved an important variable associated with health-related quality of life in Crohn's disease patients. Improving patients' self-epistemic authority can increase certainty and, thus, improve health-related quality of life.

Efficacy and Safety of Vedolizumab for Induction of Remission in Inflammatory Bowel Disease-the Israeli Real-World Experience.

BACKGROUND: Vedolizumab (VDZ) is an anti-integrin monoclonal antibody effective in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to examine the "real world" efficacy and safety of VDZ in a large national patient cohort. METHODS: Patients with inflammatory bowel disease treated with VDZ were prospectively followed for 14 weeks. Patients who completed the induction protocol (week 0/2/6/14) or discontinued the treatment before week 14 for adverse events (AEs) or primary nonresponse were included. The primary outcome was induction of clinical remission at week 14; secondary outcomes included clinical response and corticosteroid-free clinical remission. RESULTS: A total of 204 patients (CD-130, UC-69, inflammatory bowel disease-unclassified-5) from 8 centers in Israel were included. Fifteen (7.4%) of the patients were anti-tumor necrosis factor naive and 46 (35.4%) had a previous surgery. For patients with CD, 69/130 (53.1%) responded to treatment; 45 (34.6%) achieved clinical remission; and 38 (29.2%) achieved corticosteroid-free remission at week 14. Fourteen (10.7%) patients discontinued VDZ before week 14 due to primary nonresponse or AEs. For UC, 32/74 (43.2%) responded to treatment; 20 (28.4%) achieved clinical remission, and 18 (24.3%) achieved corticosteroid-free remission at week 14. Fifteen (20.3%) patients with UC did not complete the induction due to primary nonresponse or AEs. AEs were reported by 29 (14.2%) patients (CD and UC combined), most common being nasopharyngitis and skin eruptions. CONCLUSIONS: In a large real-world Israeli cohort of anti-tumor necrosis factor-experienced patients with inflammatory bowel disease, VDZ was effective and safe in induction of clinical remission and steroid-free clinical remission.

Intraepithelial lymphocytosis is a frequent finding in biopsies from ileal pouch-anal anastomoses.

Following restorative proctocolectomy with an ileal pouch-anal anastomosis, the small bowel mucosa undergoes several specific histologic adaptions, which may be unrelated to the underlying disease or symptoms of pouchitis. An increase in intraepithelial lymphocytes (IELs) has not been described as part of this spectrum. Mucosal biopsies of the ileal pouch and afferent limb of 230 patients (mean age: 45.7y [18.3-74.7], gender [female/male]: 117/113) with a functioning ileal pouch-anal anastomosis (mean time since ileostomy closure: 10.8months) and associated clinically annotated outcome data were assessed for IELs/100 enterocytes. Forty-two patients (18.3%) showed an increase in IELs (≥20 IELs/100 enterocytes [range 20-39]), in pouch and/or afferent limb biopsies. Intraepithelial lymphocytosis was more commonly observed in afferent limb compared to pouch biopsies (18.8% vs 8.3%; P = .42) and in familial adenomatous polyposis compared to ulcerative colitis patients (16% vs 8%; P = 0.36), but neither difference reached statistical significance. No cases with increased IELs displayed severe villous blunting. Increased IELs were not significantly associated with age, sex, ethnicity, smoking history, time since ileostomy, use of antibiotics, biologic agents, anti-diarrheal agents or probiotics, C-reactive protein levels or differential white cell count. None of the 42 patients with increased IELs had positive celiac serology (anti-human tissue transglutaminase IgA [ELISA] with corresponding total serum IgA). Intraepithelial lymphocytosis in pouch biopsies may represent a subclinical response to an altered bacterial microenvironment. Pathologists should be aware that intraepithelial lymphocytosis is part of the spectrum of changes in pouch biopsies, and only rarely is due to celiac disease.

The current place of probiotics and prebiotics in the treatment of pouchitis.

Pouchitis is a common complication in patients undergoing restorative proctocolectomy for ulcerative colitis. Therapeutic attempts include manipulations of pouch flora composition. In this review, we bring together the evidence supporting the use of probiotics and prebiotics in pouchitis patients, to clarify the place of these treatments in current therapeutic regimens.

Probiotics and prebiotics in Crohn's disease therapies.

Therapeutic manipulation of gut microbiota has proven valuable in the management of ulcerative colitis and pouchitis. Despite some similarities among the various inflammatory bowel conditions, the probiotics investigated thus far seem to confer little benefit in Crohn's disease. In this review, we aim to bring together the evidence available on the clinical effect of probiotics and prebioltics in Crohn's disease patients, and to clarify the place of probiotic treatment in current Crohn's therapeutic regimens.

Practice Variations in the Management of Inflammatory Bowel Disease Between Pediatric and Adult Gastroenterologists.

BACKGROUND: Different practice guidelines and consensus statements for both pediatric- and adult-onset inflammatory bowel disease exist. Although variations in medical care among gastroenterologists are common, it is unknown whether there are fundamental differences between disciplines. The primary aim of the present study was to investigate differences in common practices across disciplines. METHODS: This was a prospective, questionnaire-based survey of gastroenterologists attending gastroenterology meetings in Israel. The questionnaire covered attitudes to medical resources, diagnostic and follow-up measures as well as therapeutic approaches. RESULTS: Overall, 120 (60%) of the approached adult gastroenterologists (AGs) and 49 (75%) pediatric gastroenterologists (PGs) completed the questionnaire. The 2 groups differed significantly in various practice areas. Pediatric patients are seen more frequently and for longer appointments. PGs tend to assess thiopurine metabolites (96% vs 47%) more often during treatment. There is a significant variation in practice between groups concerning infectious serology status and vaccinations. Methotrexate in Crohn patients is used more commonly by PGs (55% vs 22%). Long-term combination therapy of thiopurines and anti-tumor necrosis factorα agents is used more often by AGs. In patients with ulcerative colitis AGs use oral 5-aminosalicylic acid once daily (51% vs 21%) and add rectal agents from the first day of treatment (72% vs 35%) more often as compared with PGs. CONCLUSIONS: This study demonstrates that common practices in inflammatory bowel disease patients differ significantly between adult and pediatric practitioners. These findings call for investigating the reasons for these differences and promoting strategies to diminish these gaps.

Uptake of influenza vaccine in ulcerative colitis.

BACKGROUND: The incidence of vaccine-preventable-disease is increasing. Current practice guidelines recommend annual influenza vaccination for all inflammatory bowel disease (IBD) patients. STUDY: Using the Business Objects database of Clalit Health Services in the Tel Aviv district we identified all patients over 18 years-old with a diagnosis of ulcerative colitis (UC) on 31.12.05. This cohort was followed until 31.12.12. Subjects over age 50 without IBD who are also targeted for influenza vaccination served as controls. The uptake of annual influenza vaccination was recorded. RESULTS: 470 UC patients were included (241 (51.3%) males, age 50.4 ± 18.4 years, disease duration 158.9 ± 86.5 months), and 2960 controls. During the years 2006, 2007, 2008, 2009, 2010, 2011 and 2012 the uptake of influenza vaccination was 101 (21.5%), 122 (26.0%), 147 (31.3%), 181 (38.5%), 177 (37.7%), 170 (36.2%) and 178 (37.9%) amongst UC patients, and 993 (33.5%), 1360 (45.9%), 1524 (51.5%), 1611 (54.4%), 1446 (48.9%), 1576 (53.2%) and 1557 (52.6%) amongst controls (p<0.0001 for every year). Independent predictors of vaccination included age (OR, 1.05; 95% CI, 1.03-1.06; p<0.001) and cardiovascular risk (OR, 1.81; 95% CI, 1.31-2.49; p<0.01). CONCLUSIONS: Although uptake influenza vaccination is consistently lower in UC compared to controls, an upward trend was observed over the study period. Public health initiatives should target this high-risk population to promote immunization.

Utilization of influenza immunization in adults with Crohn's disease-a longitudinal, population-based study.

BACKGROUND: The incidence of vaccine-preventable disease is increasing. Several guidelines recommend annual influenza vaccination for patients with inflammatory bowel disease. METHODS: Using the Business Objects database of Clalit Health Services in the Tel Aviv district we identified all patients older than 18 years with a diagnosis of Crohn's disease (CD) on December 31, 2005. This cohort was followed until December 31, 2012. Subjects without inflammatory bowel disease older than 50 years served as controls. The uptake of annual influenza vaccination was recorded. RESULTS: The study included 515 patients with CD (267 [51.8%] men, age 48.9 ± 17.5 years, disease duration 142.7 ± 56.9 months) and 2960 controls (1262 [42.6%] men, P < 0.01, age 68.9 ± 11.1 years, P < 0.01). The mean number of influenza vaccines received from 2006 to 2012 was 2.08 ± 2.46 and 3.40 ± 2.71 in CD and controls, respectively (P < 0.01). Uptake was higher in patients with CD aged 50 to 59 years and 60 to 69 years, compared with controls (0.45 ± 0.04 versus 0.24 ± 0.01, P < 0.01 and 0.64 ± 0.06 versus 0.50 ± 0.01, P = 0.04, respectively). Vaccination uptake increased significantly over time in both groups (P < 0.01). Predictors of vaccination in CD included age, female sex, immunosuppression, and cardiovascular disease. CONCLUSIONS: Uptake of influenza vaccination in CD has increased over the past 7 years, and among subjects older than 50 years, uptake remains higher in age-matched controls. Nevertheless, overall uptake remains low, particularly in young males.

Ileal pouch symptoms do not correlate with inflammation of the pouch.

BACKGROUND & AIMS: Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA). However, symptoms are not specific. The Pouchitis Disease Activity Index (PDAI) and the Pouchitis Activity Score (PAS) have been used to diagnose pouchitis. We evaluated the correlation between the clinical components of these scores and endoscopic and histologic findings. METHODS: We performed a cross-sectional study, analyzing data from 278 patients from Mount Sinai Hospital (Toronto, Canada) who had an IPAA. Patients underwent pouchoscopy with a biopsy, and data were collected on patients' clinical status. The PDAI and PAS were calculated for each subject. The Spearman rank correlation (ρ) statistical test was used to evaluate correlations between the PDAI scores and PAS, and between total scores and subscores. RESULTS: The total PDAI scores and PAS scores were correlated; the clinical components of each correlated with the total score (ρ = 0.59 and ρ = 0.71, respectively). However, we observed a low level of correlation between clinical and endoscopic or histologic subscores, with ρ of 0.20 and 0.10, respectively, by PDAI, and ρ of 0.19 and 0.04, respectively, by PAS. CONCLUSIONS: There is a low level of correlation between clinical and endoscopic and histologic subscores of patients with IPAA; clinical symptoms therefore might not reflect objective evidence of inflammation. These findings, along with evidence of correlation between total scores and clinical symptoms, indicate that these indices do not accurately identify patients with pouch inflammation. Further research is required to understand additional factors that contribute to clinical symptoms in the absence of objective signs of pouch inflammation.

Pouchitis: a practical guide.

Up to 30% of patients with ulcerative colitis (UC) will require surgical management. The established surgical procedure of choice is colectomy with ileal pouch-anal anastomosis (IPAA) for most patients. Patients with UC who have undergone IPAA are prone to develop inflammatory and non-inflammatory complications. Up to 50% of patients can be expected to experience at least one episode of pouchitis, and most of these patients will experience at least one additional acute episode within 2 years. In other cases, pouchitis might follow a relapsing-remitting course or a chronically active course. The specific aetiology of pouchitis is unknown and the optimal means of diagnosis and classification of pouchitis is not completely agreed upon. Diagnosis of pouchitis based on symptoms alone has been shown to be non-specific due to the fact that symptoms can originate from a myriad of aetiologies, not necessarily inflammatory in nature. As a result, the diagnosis of pouchitis should generally be based on the appropriate constellation of symptoms, combined with endoscopic and histological assessment. Due to the frequently relapsing course of pouchitis, and the fact that the aetiology and pathogenesis are not entirely clear, the long-term management can sometimes be challenging. This review outlines the features suggestive of deviation from 'normal' pouch function and provides an approach to the optimal use of diagnostic modalities and medical therapies to treat pouchitis in its various forms.