关键词： SARS-CoV-2 Vaccine   Inflammatory Bowel Disease   Effectiveness   Immunosuppressive Medications   Veterans Affairs Healthcare System  

摘要： BACKGROUND & AIMS: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly expanded;however, clinical trials excluded patients taking immunosuppressive medications such as those with inflammatory bowel disease (IBD). Therefore, we explored real-world effectiveness of coronavirus disease 2019 (COVID-19) vaccination on subsequent infection in patients with IBD with diverse exposure to immunosuppressive medications. METHODS: This was a retrospective cohort study of patients in the Veterans Health Administration with IBD diagnosed before December 18, 2020, the start date of the Veterans Health Administration patient vaccination program. IBD medication exposures included mesalamine, thiopurines, anti-tumor necrosis factor biologic agents, vedolizumab, ustekinumab, tofacitinib, methotrexate, and corticosteroid use. We used inverse probability weighting and Cox's regression with vaccination status as a time-updating exposure and computed vaccine effectiveness from incidence rates. RESULTS: The cohort comprised 14,697 patients, 7321 of whom received at least 1 vaccine dose (45.2% Pfizer, 54.8% Moderna). The cohort had median age 68 years, 92.2% were men, 80.4% were White, and 61.8% had ulcerative colitis. In follow-up data through April 20, 2021, unvaccinated individuals had the highest raw proportion of SARS-CoV-2 infection (197 [1.34%] vs 7 [0.11%] fully vaccinated). Full vaccination status, but not partial vaccination status, was associated with a 69% reduced hazard of infection relative to an unvaccinated status (hazard ratio, 0.31, 95% confidence interval, 0.17-0.56;P < .001), corresponding to an 80.4% effectiveness. CONCLUSIONS: Full vaccination (> 7 days after the second dose) against SARS-CoV-2 infection has an similar to 80.4% effectiveness in a broad IBD cohort with diverse exposure to immunosuppressive medications. These results may serve to increase patient and provider willingness to pursue vaccination in these settings.

关键词： adverse events   biologic   Crohn disease   tofacitinib   ulcerative colitis  

摘要： Objectives: Tofacitinib, a selective Janus kinase inhibitor, effectively induces and maintains remission in adults with inflammatory bowel disease (IBD), but data are limited in children. This study aimed to evaluate the efficacy and safety of tofacitinib for medically refractory pediatric-onset IBD. Methods: This single-center retrospective study included subjects ages 21 years and younger who started tofacitinib for medically refractory IBD. Clinical activity indices, clinical response, steroid-free remission, biochemical response, and adverse events (AEs) were evaluated over 52 weeks. Results: Twenty-one subjects, 18 with ulcerative colitis or indeterminate IBD, received tofacitinib. At the end of the 12-week induction period, 9 out of 21 (42.9%) subjects showed clinical response and 7 out of 21 (33.3%) were in steroid-free remission. Of evaluable subjects at 52 weeks, 7 out of 17 (41.2%) showed clinical response and were in steroid-free remission. Of those remaining on tofacitinib at 1 year, none required concomitant systemic corticosteroids. Tofacitinib was discontinued in 8 subjects because of refractory disease, including 8 who ultimately underwent colectomy, and in 1 subject who developed a sterile intra-abdominal abscess. There were no instances of thrombi, zoster reactivation, or clinically significant hyperlipidemia, all of which were AEs of interest. Conclusions: There is limited experience with tofacitinib in pediatric IBD. In this cohort, tofacitinib induced rapid clinical response with sustained efficacy in nearly half of subjects. This study provides encouraging evidence for the efficacy and safety of tofacitinib as part of the treatment paradigm for young individuals with moderate-to-severe IBD. Larger, well-powered, prospective studies are warranted.

关键词： Molecular Medicine   Antibodies   Cancer Research   Pharmacotherapy  

摘要： In the last two decades, understanding of inflammatory bowel disease (IBD) immunopathogenesis has expanded considerably. Histopathological examination of the intestinal mucosa in IBD demonstrates the presence of a chronic inflammatory cell infiltrate. Research has focused on identifying mechanisms of immune cell trafficking to the gastrointestinal tract that may represent effective gut-selective targets for IBD therapy whilst avoiding systemic immunosuppression that may be associated with off-target adverse effects such as infection and malignancy. Integrins are cell surface receptors that can bind to cellular adhesion molecules to mediate both leukocyte homing and retention. In 2014, Vedolizumab (Entyvio(R)) was the first anti-integrin (anti-alpha 4ss7 monoclonal antibody) treatment to be approved for use in IBD. Several other anti-integrin therapies are currently in advanced stages of development, including novel orally administered small-molecule drugs. Drugs targeting alternative trafficking mechanisms such as mucosal addressin cellular adhesion molecule-1 and sphingosine-1-phosphate receptors are also being evaluated. Here, we summarise key established and emerging therapies targeting leukocyte trafficking that may play an important role in realising the goal of stratified precision medicine in IBD care.

关键词： Biologics   COVID-19   SARS-CoV-2   Inflammatory bowel disease   Mortality  

摘要： Background Patients with Inflammatory bowel disease (IBD) remain highly concerned that either their disease or medications-namely, biologics-may increase the risk of severe coronavirus-2019 (COVID-19). We aimed to assess the safety of biologics in Inflammatory bowel disease (IBD) patients with COVID-19. Methods We systematically reviewed multiple databases to find relevant articles reporting the effect of biologics on "severe" COVID-19 in IBD patients. Those in the form of case series (> 10 patients), case-control, and cohort studies were included. Severe COVID-19 was defined as intensive care unit (ICU) admission, mechanical ventilation, and/or mortality. Pooled analysis with multivariate regression was performed. Results A total of 12 studies with 2681 patients were included. The proportion of females was (48.3%, 95% confidence interval (CI) 47.0-49.5%). The proportion of UC patients was (44.8%, 95% CI 41.0-48.5%). Overall, in IBD patients, the need for mechanical ventilation, intensive care unit (ICU) admission, and mortality was 5.1%, 6.1%, and 4.5%, respectively. Use of biologics did not show a moderating effect on mechanical ventilation (p = 0.68), ICU admission (p = 0.27), or mortality (p = 0.20). Conclusions Our findings advocate for the continued biologic therapy in IBD patients during the COVID-19 pandemic. Nevertheless, the incidence, severity, and outcomes related to COVID-19 in IBD patients' needs to be reassessed as data continues to emerge.

关键词： Inflammatory Bowel Disease   Colorectal Cancer Screening   Chromoendoscopy   Colonoscopy  

摘要： Improvements in disease management, as well as endoscopic technology and quality, have dramatically changed the way in which we conceptualize and manage inflam-matory bowel disease-related dysplasia over the past 20 years. Based on evolving literature, we propose a conceptual model and best practice advice statements for the prevention, detection, and management of colorectal dysplasia in people with inflammatory bowel disease. This expert review was commissioned and approved by the American Gastroenterological Association Institute Clinical Practice Updates Committee and the American Gastroenterological Association Governing Board to provide timely guidance on a topic of high clinical importance to the American Gastroenterological Association membership. It underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology.

关键词： children   Epstein-Barr virus   immunomodulator therapy   inflammatory bowel disease  

摘要： The use of thiopurine therapy in Epstein-Barr virus (EBV)-naive inflammatory bowel disease (IBD) patients remains controversial due to a risk of EBV-associated complications. We evaluated EBV status and outcomes within our paediatric IBD population over an 8-year period;finding that 217 of 409 (53%) screened patients were seropositive for EBV at IBD diagnosis;that thiopurines were used in 189 of 217 (87%) seropositive and 159 of 192 (83%) seronegative patients (P = 0.22);and that 7 of 192 (4%) previously seronegative patients subsequently tested positive for EBV with 6 of 7 (86%) patients having concurrently recorded thiopurine use. All six patients continued thiopurine with/without a period of cessation;no EBV-associated lymphoproliferative disorders/serious complications were recorded within our cohort. A significant proportion of our patients would not receive thiopurine therapy should their use be avoided in EBV-negative patients (47%) or seronegative males (30%). The small but significant risks of thiopurine treatment must be balanced against the potential benefits of successful IBD management;further research into this is required.

关键词： Pharmacotherapy   Pharmacology/Toxicology   Internal Medicine  

关键词： Crohn's disease   Ulcerative colitis   Children   Vedolizumab  

摘要： Vedolizumab is a humanised monoclonal antibody that binds to integrin alpha 4 beta 7 expressed in T-cells, inhibiting its binding to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is specifically expressed in the small intestine and colon, playing a fundamental role in T-cell migration to the gastrointestinal tract. Vedolizumab has been shown to be effective in treating adults with inflammatory bowel disease;however, efficacy data for paediatric use are scarce. The objective of the present study was to assess the effectiveness and safety of vedolizumab for inducing and maintaining clinical remission in children with inflammatory bowel disease. We conducted a retrospective multicentre study of patients younger than 18 years with inflammatory bowel disease refractory to anti-tumour necrosis factor alpha (anti-TNF-alpha) drugs, who underwent treatment with vedolizumab. Clinical remission was defined as a score < 10 points in the activity indices. We included 42 patients, 22 of whom were male (52.3%), with a median age of 13.1 years (IQR 10.2-14.2) at the start of treatment. Of the 42 patients, 14 (33.3%) had Crohn's disease (CD) and 28 (66.7%) had ulcerative colitis (UC). At the start of treatment with vedolizumab, the Paediatric Crohn's Disease Activity Index was 36 (IQR 24-40) and the Paediatric Ulcerative Colitis Activity Index was 47 (IQR 25-65). All of them had received prior treatment with anti-TNF and 3 patients ustekinumab. At week 14, 69% of the patients responded to the treatment (57.1% of those with UC and 75% of those with UC;p=0.238), and 52.4% achieved remission (35.7% with CD and 60.7% with UC;p=0.126). At 30 weeks, the response rate was 66.7% (46.2% and 78.3% for CD and UC, respectively;p=0.049), and 52.8% achieved remission (30.8% and 65.2% for CD and UC, respectively;p=0.047). Among the patients with remission at week 14, 80% of the patients with CD and 84.5% of those with UC maintained the remission at 52 weeks. Adverse effects were

关键词： oncostatin-M   pediatric inflammatory bowel disease   refractory disease   tumor necrosis factor antagonist  

摘要： Objectives: This study aimed to determine whether mRNA expression of oncostatin-M (OSM) and its receptor (OSMR) in initial, pre-treatment intestinal biopsies is predictive of response to tumor necrosis factor antagonists (anti-TNF) in a pediatric inflammatory bowel disease (IBD) cohort. Secondary outcomes correlated OSM and OSMR expression with demographic variables;IBD type, extent, phenotype, and severity;laboratory values;and endoscopic findings. Methods: A retrospective chart review was conducted on 98 pediatric patients. Patients' clinical courses were stratified as follows: failed anti-TNF (n = 14), quiescent on anti-TNF (n = 36), anti-TNF naive (n = 19), and age-matched non-IBD controls (n = 29). The mRNA from each patient's pre-treatment ileal or colonic biopsy was isolated, and expression of OSM and OSMR was analyzed. Results: There was no difference in OSM or OSMR expression among the three IBD groups;however, expression was significantly higher in patients with IBD than non-IBD controls (P < 0.001). OSM and OSMR were more highly expressed in patients with ulcerative colitis (UC) with a Mayo score of 3 (P = 0.0092 and P = 0.0313, respectively). High OSM expression correlated with severe disease activity indices at diagnosis (P = 0.002), anemia at diagnosis (P = 0.0236), and need for immunomodulators (P = 0.0193) and steroids (P = 0.0273) during patients' clinical courses. Conclusions: OSM and OSMR expression were not predictive of response to anti-TNF in our pediatric cohort. OSM expression did correlate with IBD compared with healthy controls as well as with several clinical indicators of severe IBD.

摘要： Background Poor dietary intake is associated with the development of malnutrition, micronutrient deficiencies, anaemia and osteoporosis in individuals with inflammatory bowel disease. While trials are underway to manipulate the diet of people with IBD, there has been no comprehensive systematic review of the dietary intake of adults with IBD. Aims To conduct a systematic evaluation and meta-analysis of the dietary intake of adults with IBD, including macronutrients, micronutrients and food group data. Methods CINAHL, Embase, Medline and Scopus were searched from 1 January 2000 to 25 September 2020 for cohort, case-control or cross-sectional studies that reported usual dietary intake in adults. Data were pooled and reported as weighted mean intake for: all adults with IBD;Crohn's disease;ulcerative colitis;active disease;remission;males;females. A random-effects meta-analysis model compared intake with healthy individuals. Results Forty studies were identified and 19 were included in the meta-analysis. All subgroups of adults with IBD consumed inadequate energy (mean intake in adults with IBD 1980 +/- 130 kcal), fibre (14 +/- 4 g), folate (246 +/- 33 mg) and calcium (529 +/- 114 mg) per day. Intake of breads and cereals, legumes, fruit, vegetables and dairy were inadequate. Compared to healthy individuals, adults with IBD consume significantly less dietary fibre (SMD -0.59;95% CI: -0.73, -0.46). Conclusions This review provides improved clarity about the dietary intake of adults with IBD. Future attention is required to improve diet quality and increase understanding of factors influencing dietary intake in IBD.