Irish data on the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease.

SUMMARY: This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Key SummaryVedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBDThis study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.

Clinical Outcome of Patients with Raised Intraepithelial Lymphocytes with Normal Villous Architecture on Duodenal Biopsy.

INTRODUCTION: The finding of a raised intraepithelial lymphocytes (IELs) count with normal villous architecture is of sufficient clinical importance to be reported in routine duodenal biopsies. AIM: To study the clinical and demographic data of patients with isolated increased IELs on duodenal biopsy. METHODS: A single-tertiary-centre retrospective study was carried out with a review of medical records of patients with increased IELs. Patients from 2012 to 2014, >18 years with at least one biopsy from the second part of the duodenum with increased IELs; defined as >25 IELs/100 enterocytes, with preserved villous architecture were identified from our histopathology database with exclusion of patients with coeliac disease (CD).Clinical and demographic data were recorded following a chart review. CD was diagnosed by the attending physician based on the Physician Global Assessment. Data was compared between groups using a Student t test and ORs were calculated as appropriate. Statistical significance was set a priori at p < 0.05. RESULTS: Over 24 months, 6,244 patients were found to have duodenal biopsies and 114 (1.8%) had isolated increased IELs. Of the patients with increased IELs, the mean age was 50 years and 34 (30%) were male. Follow-up was available in 75 (65%) of these and CD was subsequently diagnosed in 32% (n = 24). CD was associated with the female gender (22 out of 24 vs. 39 out of 51, OR 7.5, older age 55 vs. 41 years, p < 0.04), and higher IEL count with an IEL of >40 in 11 out of 24 (46%) with CD vs. 12 out of 51 (24%) without CD, p = 0.0006. CONCLUSION: It is a non-specific but important finding, as it can have clinical implications.

Inflammatory Bowel Disease Disability Index is a valid and reliable measure of disability in an English-speaking hospital practice and predicts long-term requirement for treatment escalation.

Objective: The Inflammatory Bowel Disease Disability Index (IBD-DI) was developed according to WHO standards and has been validated in population-based cohorts. However, there are limited data on its relationship to various psychosocial and economic variables or its relevance to hospital clinical practice. The study aims were to determine the validity and reliability of the IBD-DI in an English-speaking hospital out-patient population and to evaluate its association with short and long-term disease activity. Design/Methods: 329 subjects were enrolled in a cross-sectional and longitudinal study assessing the IBD-DI and a range of quality of life, work impairment, depression, anxiety, body image, interpersonal, self-esteem, disease activity, symptom scoring scales in addition to long-term outcome. Results: The IBD-DI had adequate structure, was internally consistent and demonstrated convergent and predictive validity and was reliable in test-retest study. Disability was related to female sex (p=0.002), antidepressant use (p<0.001), steroid use (p<0.001) and disease activity (p<0.001). Higher IBD-DI scores were associated with long-term disease activity and need for treatment escalation in univariate (p<0.001) and multivariate (p=0.002) analyses. Conclusion: The IBD-DI is a valid and reliable measure of disability in English-speaking hospital populations and predicts long-term requirement for treatment escalation.

The effects of dairy on the gut microbiome and symptoms in gastrointestinal disease cohorts: a systematic review.

Bovine dairy foods provide several essential nutrients. Fermented bovine dairy foods contain additional compounds, increasing their potential to benefit gastrointestinal health. This review explores the effects of dairy consumption on the gut microbiome and symptoms in gastrointestinal disease cohorts. Human subjects with common gastrointestinal diseases (functional gastrointestinal disorders and inflammatory bowel disease) or associated symptoms, and equivalent animal models were included. A systematic literature search was performed using PubMed, Embase and Web of Science. The search yielded 3014 studies in total, with 26 meeting inclusion criteria, including 15 human studies (1550 participants) and 11 animal studies (627 subjects). All test foods were fermented bovine dairy products, primarily fermented milk and yogurt. Six studies reported increases in gastrointestinal bacterial alpha diversity, with nine studies reporting increases in relative Lactobacillus and Bifidobacterium abundance. Six studies reported increases in beneficial short-chain fatty acids, while three reported decreases. Gastrointestinal symptoms, specifically gut comfort and defecation frequency, improved in 14 human studies. Five animal studies demonstrated reduced colonic damage and improved healing. This review shows fermented bovine dairy consumption may improve gut microbial characteristics and gastrointestinal symptoms in gastrointestinal disease cohorts. Further human intervention studies are needed, expanding test foods and capturing non-self-reported gastrointestinal measures.

Implementation of BSG/ACPGBI/PHE polypectomy surveillance guidelines safely reduces the burden of surveillance in a screening cohort: a virtual model study.

OBJECTIVE: To evaluate the impact of British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England (BSG/ACPGBI/PHE) 2019 polypectomy surveillance guidelines within a national faecal immunochemical test-based bowel cancer screening (BS) cohort on surveillance activity and detection of pathology by retrospective virtual application. DESIGN: A retrospective review of BS colonoscopies performed in 2015-2016 with 5 years prospective follow-up in single institution. Index colonoscopies were selected. Incomplete colonoscopies were excluded. Histology of all resected polyps was reviewed. Surveillance intervals were calculated according to BSG/ACPGBI/PHE 2019 guidelines and compared with pre-existing 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis' (EUQA 2013). Total number of colonoscopies deferred by virtual implementation of BSG/ACPGBI/PHE 2019 guidelines were calculated. Pathology identified on procedures that would have been deferred was reviewed. RESULTS: Total number of index BS colonoscopies performed in 2015-2016 inclusive was 890. 115 were excluded (22 no caecal intubation, 51 inadequate bowel preparation, 56 incomplete polyp clearance). N=509 colonoscopies were scheduled within a 5-year interval following index colonoscopy surveillance rounds based on EUQA guidelines. Overall, volume of surveillance was significantly reduced with retrospective application of BSG/ACPGBI/PHE 2019 guidelines (n=221, p<0.0001). No cancers were detected within the 'potentially deferred' procedures who attended for follow-up (n=330) with high-risk findings found in<10% (n=30) of colonoscopies within the BSG/ACPGBI/PHE cohort. CONCLUSION: BSG/ACPGBI/PHE 2019 guidelines safely reduce the burden of colonoscopy demand with acceptable pathology findings on deferred colonoscopies.

Reduced Serological Response to COVID-19 Booster Vaccine is Associated with Reduced B Cell Memory in Patients With Inflammatory Bowel Disease; VARIATION [VAriability in Response in IBD AgainsT SARS-COV-2 ImmunisatiON].

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on responses after the third vaccine against SARS-CoV-2. METHODS: This was a prospective multicentre observational study of patients with IBD [n = 202] and healthy controls [HC, n = 92]. Serological response to vaccination was assessed by quantification of anti-spike protein [SP] immunoglobulin [Ig]G levels [anti-SPIgG] and in vitro neutralization of binding to angiotensin-converting enzyme 2 [ACE2]. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture. RESULTS: Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs [7862 vs 19 622 AU/mL, p < 0.001] as was ACE2 binding inhibition [p < 0.001]. IBD patients previously infected with COVID-19 [30%] had similar quantitative antibody response as HCs previously infected with COVID-19 [p = 0.12]. Lowest anti-SP IgG titres and neutralization were seen in IBD patients on anti-tumour necrosis factor [anti-TNF] agents, without prior COVID-19 infection, but all IBD patients show an attenuated vaccine response compared to HCs. Patients with IBD have reduced memory B-cell populations and attenuated B-cell responses to SARS-CoV-2 antigens if not previously infected with COVID-19 [p = 0.01]. Higher anti-TNF drug levels and zinc levels <65 ng/ml were associated with significantly lower serological responses. CONCLUSIONS: Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.

Mucosal Healing in Crohn's Disease: Bull's Eye or Bust? "The Pro Position".

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications. SUMMARY: Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge. KEY MESSAGES: Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention.

Reduced Serological Response to COVID-19 Vaccines in Patients with IBD is Further Diminished by TNF Inhibitor Therapy; Early Results of the VARIATION study [VAriability in Response in IBD Against SARS-COV-2 ImmunisatiON].

BACKGROUND AND AIMS: Evidence suggests patients with inflammatory bowel disease [IBD] receiving TNF antagonists have attenuated response to vaccination against COVID-19. We sought to determine the impact of IBD and of various medications for treatment of IBD on antibody responses to vaccination against COVID-19. METHODS: Patients with IBD [n = 270] and healthy controls [HC, n = 116] were recruited prospectively, and quantitative antibody responses were assessed following COVID-19 vaccination. The impact of IBD and of medications for treatment of IBD on vaccine response rates was investigated. RESULTS: Of HC, 100% seroconverted following complete vaccination with two vaccine doses; 2% of patients with IBD failed to seroconvert. Median anti-spike protein [SP] immunoglobulin [Ig]G levels following complete vaccination in our IBD cohort was significantly lower than among HC [2613 AU/mL versus 6871 AU/mL, p ≤0.001]. A diagnosis of IBD was independently associated with lower anti-SP IgG levels [ß coefficient -0.2, p = 0.001]. Use of mRNA vaccines was independently associated with higher anti-SP IgG levels [ß coefficient 0.25, p ≤0.001]. Patients with IBD receiving TNF inhibitors had significantly lower anti-SP IgG levels [2445 AU/mL] than IBD patients not receiving TNF inhibitors [3868 AU/mL, p ≤0.001]. Patients with IBD not receiving TNF inhibitors still showed attenuated responses compared with HC [3868 AU/mL versus 8747 AU/mL, p = 0.001]. CONCLUSIONS: Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Use of anti-TNF therapy negatively affects anti-SP IgG levels further. Patients who do not seroconvert following vaccination are a particularly vulnerable cohort. Impaired responses to vaccination in our study highlight the importance of booster vaccination programmes for patients with IBD.

Review Article: vaccination for patients with inflammatory bowel disease during the COVID-19 pandemic.

BACKGROUND: Poor immune responses are frequently observed in patients with inflammatory bowel disease (IBD) receiving established vaccines; risk factors include immunosuppressants and active disease. AIMS: To summarise available information regarding immune responses achieved in patients with IBD receiving established vaccines. Using this information, to identify risk factors in the IBD population related to poor vaccine-induced immunity that may be applicable to vaccines against COVID-19. METHODS: We undertook a literature review on immunity to currently recommended vaccines for patients with IBD and to COVID-19 vaccines and summarised the relevant literature. RESULTS: Patients with IBD have reduced immune responses following vaccination compared to the general population. Factors including the use of immunomodulators and anti-TNF agents reduce response rates. Patients with IBD should be vaccinated against COVID-19 at the earliest opportunity as recommended by International Advisory Committees, and vaccination should not be deferred because a patient is receiving immune-modifying therapies. Antibody titres to COVID-19 vaccines appear to be reduced in patients receiving anti-TNF therapy, especially in combination with immunomodulators after one vaccination. Therefore, we should optimise any established risk factors that could impact response to vaccination in patients with IBD before vaccination. CONCLUSIONS: Ideally, patients with IBD should be vaccinated at the earliest opportunity against COVID-19. Patients should be in remission and, if possible, have their corticosteroid dose minimised before vaccination. Further research is required to determine the impact of different biologics on vaccine response to COVID-19 and the potential for booster vaccines or heterologous prime-boost vaccinations in the IBD population.

Predicting pathology on small bowel capsule endoscopy: a good FIT.

Background and study aims Small bowel capsule endoscopy [SBCE) has an established role in investigating suspected small bowel bleeding [SSBB). Identification of a biomarker to predict pathology would maximize utility of this valuable diagnostic modality. This study aimed to investigate if fecal immunochemical test [FIT) could predict likelihood of small bowel pathology on SBCE. Patients and methods Patients referred for SBCE to investigate anaemia or suspected small bowel bleeding were prospectively recruited. All patients had negative upper and lower endoscopy prior to referral. A FIT ≥ 45 ug Hb/g was considered positive. SBCE was positive if a potential source of SSBB was identified. The primary endpoint was correlation between FIT and positive SBCE. Secondary endpoints were correlation between anemia and SBCE and a combination of anemia plus FIT and SBCE. Results Fifty-one patients were included in the final study cohort. 29.4 % had a positive FIT, 33.3 % were anemic, and 25.5 % patients had significant SBCE findings. There was a statistically significant association between positive FIT and pathology on SBCE (OR 12, 95 % CI [2.8 - 51.9), P  = 0.001). Sensitivity and specificity of positive FIT in predicting SBCE findings were 69 % and 84 %, respectively. A normal Hb had an NPV of 83 % (OR 0.30, P  = 0.09). Combining Hb and FIT was statistically significant in predicting pathology on SBCE (OR 9.14, 67 % PPV, 82 % NPV, P  = 0.025). Conclusion FIT ≥ 45 ug Hb/g is a useful tool in predicting small bowel pathology on SBCE. Use of this biomarker alone, or in combination with serum haemoglobin, has value as a screening tool and may help to better triage patients referred for SBCE.

Same-day colon capsule endoscopy is a viable means to assess unexplored colonic segments after incomplete colonoscopy in selected patients.

BACKGROUND: Same-day colon capsule endoscopy (CCE) immediately following incomplete optical colonoscopy (OC) would have a number of advantages for patients, while also presenting unique procedural challenges including the effect of sedation on capsule propulsion and patient tolerance of protracted preparation and fasting. AIM: The aim of this article is to prospectively assess the efficacy of same-day CCE after incomplete OC in an unselected patient cohort. METHODS: This was an observational, prospective, single-centre study of CCE post-incomplete colonoscopies. Patients with an incomplete OC for any reason other than obstruction or inadequate bowel preparation were recruited. CCE was performed after a minimum of a one-hour fast. Once the patient was fully alert, intravenous metoclopramide was administered after capsule ingestion when possible, and a standard CCE booster protocol was then followed. Relevant clinical information was recorded. CCE completion rates, findings and their impact, and adverse events were noted. RESULTS: Fifty patients were recruited, mean age = 57 years and 66% (n = 32) were female. Seventy-six per cent (n = 38) of CCEs were complete; however, full colonic views were obtained in 84% (n = 42) of cases. Patients > 50 years of age were five times more likely to have an incomplete CCE and there was also a trend towards known comorbidities associated with hypomobility having reduced excretion rates. Overall diagnostic yield for CCE in the unexplored segments was 74% (n = 37), with 26% (n = 13) of patients requiring significant changes in management based on CCE findings. The overall incremental yield was 38%. CCE findings were normal 26% (n = 13), polyps 38% (n = 19), inflammation 22% (n = 11), diverticular disease 25 (n = 12), angiodysplasia 3% (n = 1) and cancer 3% (n = 1). Significant small bowel findings were found in three (6%) cases, including Crohn's disease and a neuroendocrine tumour. A major adverse event occurred in one patient (2%), related to capsule retention. CONCLUSION: Same-day CCE is a viable alternative means to assess unexplored segments of the colon after incomplete OC in selected patients.

Golimumab effectiveness and safety in clinical practice for moderately active ulcerative colitis.

BACKGROUND AND AIMS: Golimumab (GLB) is an antitumour necrosis factor-α (anti-TNF) therapy that has shown efficacy as induction and maintenance therapy for ulcerative colitis (UC). We aimed to describe the outcome of GLB therapy for UC in a real-world clinical practice. PATIENTS AND METHODS: Consecutive patients receiving GLB for UC in six Irish Academic Medical Centres were identified. The primary study endpoint was the 6-month corticosteroid-free remission rate. The secondary endpoints included the 3-month clinical response, time free of GLB discontinuation and adverse events. RESULTS: Seventy-two patients were identified [57% men; median (range) age of 41.4 years (20.3-76.8); disease duration 6.6 years (0-29.9); follow-up 8.7 months (0.4-39.2)]. Sixty-four percent of patients were anti-TNF naive. The 3-month clinical response and the 6-month corticosteroid-free remission rates were 55 and 39%, respectively. Forty-four percent of patients discontinued GLB during the follow-up, median (95% confidence interval) time to GLB discontinuation 18.7 months (9.2-28.1). A C-reactive protein more than 5 mg/l at baseline was associated with failure to achieve 6-month corticosteroid-free remission and a shorter time to GLB discontinuation, odds ratio 0.2 (0.1-0.7), P=0.008, and hazard ratio (95% confidence interval) 2.8 (1.3-5.7), P=0.007, respectively. Adverse events occurred in 7% of patients (n=5), all of which were minor and self-limiting. CONCLUSION: These real-world clinical data suggest that GLB is an effective and safe therapy for a UC cohort with significant previous anti-TNF exposure. An elevated baseline C-reactive protein, likely reflective of increased inflammatory burden, is associated with a reduced likelihood of a successful outcome of GLB therapy.

Post-ERCP Emphysematous Cholecystitis in a Young Woman: A Rare and Potentially Fatal Complication.

A 45-year-old woman with suspected Functional Biliary Sphincter Disorder (FBSD) developed Clostridium perfringens related emphysematous cholecystitis after ERCP. A low index of suspicion for emphysematous cholecystitis in this young, otherwise healthy woman led to a significant delay in making the correct diagnosis, and air in the gallbladder was wrongly attributed to a possible gallbladder perforation. ERCP is associated with significant risks, particularly in patients with FBSD, where diagnostic uncertainty renders the balance of risk versus benefit even more critical. Post-ERCP emphysematous cholecystitis secondary to Clostridium perfringens is a rare but potentially fatal complication.