Effectiveness and safety of vedolizumab for maintenance treatment in inflammatory bowel disease—The Israeli real world experience

Introduction

Several real-world experience (RWE) studies with vedolizumab (VDZ) for induction of remission in inflammatory bowel diseases (IBD) have been published; however, long-term RWE data is scarce.

Patient preferences for inflammatory bowel disease treatment objectives

BackgroundThere is currently little evidence about what treatment objectives most interest patients with inflammatory bowel disease (IBD).AimsTo determine patient preferences regarding IBD treatment objectives, specially the attributes they value most and the symptoms to be controlled as a priority.MethodsProspective, observational, anonymous study conducted in 117 outpatients with Crohn’s disease or ulcerative colitis.ResultsThe most important treatment objectives from the patients’ perspective were: improving quality of life (40.2% of patients), and completely resolving symptoms (33.3%). Only 12.8% of patients indicated having a completely normal colonoscopy as a preferred objective. The symptoms the patients considered to be most important when prioritizing their control were: abdominal pain (23.1% of patients), and bowel movement urgency (17.1%). The preferred treatment objectives were similar for Crohn’s disease and ulcerative colitis patients.ConclusionsImproving quality of life and completely controlling symptoms are the priority treatment objectives for IBD patients, with abdominal pain being the most important symptom. Conversely, therapeutic objective target goals proposed by physicians, such as healing the mucosal lesions, are not a priority for most patients. This indicates that there are discrepancies between patient and physician expectations, which should be taken into account if a patient-centered care model is to be implemented.     

Anti-integrin therapy for inflammatory bowel disease

In inflammatory bowel disease(IBD), tumor necro-sis factor plays an important role in mediating infla-mmation, but several other pathways are also involved in eliciting an inflammatory response. One such pathway is the invasion of the intestinal mucosa by leukocytes. Leukocytes within the systemic circulation move to sites of inflammation, and blocking this pathway could be an important treatment strategy for IBD. Anti-integrin therapy blocks the action of integrin on the surface of circulating immune cells and endothelial cell adhesion molecules, thereby inhibiting the interactions between leukocytes and intestinal blood vessels. Natalizumab, which acts on α4-integrin, was the first such drug to be approved for Crohn's disease, but its use is limited due to the risk of progressive multifocal leukoencephalopathy. Vedolizumab produces few systemic adverse effects because it acts on gut-trophic α4β7 integrin, and has been approved and is being used to treat IBD. Currently, several anti-integrin drugs, including etrolizumab, which acts on β7-integrin, and PF-00547569, which targets mucosal addressin cell adhesion molecule-1, are undergoing clinical trials and the results are being closely watched.     

Obesity and novel management of inflammatory bowel disease

Obesity is prevalent within the inflammatory bowel disease(IBD) population,particularly in newly developed countries.Several epidemiological studies have suggested that 15%-40% of IBD patients are obese,and there is a potential role of obesity in the pathogenesis of IBD.The dysfunction of mesenteric fat worsens the inflammatory course of Crohn’s disease and may induce formation of strictures or fistulas.Furthermore,obesity may affect the disease course or treatment response of IBD.Given the incr...     

炎症性肠病相关性肝病的研究进展

炎症性肠病(inflammatory bowel disease,IBD)是一种累及回肠、结肠、直肠的特发性炎症性疾病,本病主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。除常见的消化道症状外,研究发现IBD合并肝脏疾病较为常见,是IBD常见的肠外表现之一,其严重影响IBD的预后与转归。本文就IBD相关性肝病的分类和总结作一概述,以期为IBD及其肝脏病变的临床诊疗提供参考。     

Successful outcome of the transitional process of inflammatory bowel disease from pediatric to adult age: A five years experience

Introduction and aim

The transitional process of young patients affected by inflammatory bowel disease from pediatric to adult care is a crucial step. Our study aimed to investigate the 1-year success outcome of this transitional process.

Recent results of laparoscopic surgery in inflammatory bowel disease

Inflammatory bowel diseases are an ideal indication for the laparoscopic surgical approach as they are basically benign diseases not requiring lymphadenectomy and extended mesenteric excision;well-established surgical procedures are available for the conventional approach.Inflammatory alterations and fragility of the bowel and mesentery,however,may demand a high level of laparoscopic experience.A broad spectrum of operations from the rather easy enterostomy formation for anal Crohn’s disease(CD)to restorati...     

Dysplasia and colorectal cancer surveillance in inflammatory bowel disease

Introduction: Inflammatory bowel disease (IBD) patients are at an increased risk of developing colorectal cancer (CRC), a devastating complication of which intestinal dysplasia is the precursor. Considerable progress has been made to determine CRC risk in IBD, identification & management of dysplasia and preventative methods. Traditionally, surveillance colonoscopies with random colonic biopsies was used. However recent data suggests that chromoendoscopy is a better method of surveillance. Using 5-aminosalicylic acid agents primarily for chemoprevention is an ongoing debate however, when prescribed along with other strategies to control inflammation, their use is considered of benefit. This review presents current understanding of risk factors of neoplasia focusing on dysplasia and preventive strategies.

Areas covered: PubMed search was done using key words to assess current evidence. Along with genetics, risk factors, strategies that modify the risk of dysplasia, and CRC in IBD are discussed in detail.

Expert commentary: The role of our strategies in modifying CRC risk needs further assessment. Future research should aim to fill knowledge gaps such as high quality evidence for Chromoendoscopy and development of molecular markers for dysplasia detection. Our ultimate goal would be to eliminate CRC and is possible by better understanding of key pathogenic mechanisms in IBD.     

First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases: A 2020 Delphi consensus

Ulcerative colitis and Crohn’s disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract. The incidence and prevalence are on the rise worldwide, and the heterogeneity between patients and within individuals over time is striking. The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients. This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence- and expert opinion-based recommendations. Comprehensive up-to-date guidance is provided regarding diagnosis, evaluation of disease severity, appropriate and timely use of different investigations, choice of appropriate therapy for induction and remission phase according to disease severity, and management of main complications.     

Minimum sample size estimates for trials in inflammatory bowel disease: A systematic review of a support resource

BACKGROUNDOf 25% of randomised controlled trials (RCTs) on interventions for inflammatory bowel disease (IBD) have no power calculation. AIMTo systematically review RCTs reporting interventions for the management of IBD and to produce data for minimum sample sizes that would achieve appropriate power using the actual clinical data.METHODSWe included RCTs retrieved from Cochrane IBD specialised Trial register and CENTRAL investigating any form of therapy for either induction or maintenance of remission against control, placebo, or no intervention of IBD in patients of any age. The relevant data was extracted, and the studies were grouped according to the intervention used. We recalculated sample size and the achieved difference, as well as minimum sample sizes needed in the future.RESULTSA total of 105 trials were included. There was a large discrepancy between the estimated figure for the minimal clinically important difference used for the calculations (15% group differences observed vs 30% used for calculation) explaining substantial actual sample size deficits. The minimum sample sizes indicated for future trials based on the 25 years of trial data were calculated and grouped by the intervention. CONCLUSIONA third of intervention studies in IBD within the last 25 years are underpowered, with large variations in the calculation of sample sizes. The authors present a sample size estimate resource constructed on the published evidence base for future researchers and key stakeholders within the IBD trial field.     

HLA-DQ: Celiac disease vs inflammatory bowel disease

AIM To determine the genetic predisposition to celiacdisease(Ce D) in inflammatory bowel disease(IBD) patients by quantifying the frequency of Ce D-related human leucocyte antigen(HLA)(HLA-Ce D: HLA-DQ2 and-DQ8) in IBD patients globally, by type of IBD and gender, and by calculating the protective/risk contribution of these haplotypes in the development of the IBD disease.METHODS We conducted a prospective study with IBD patients from our Unit. Clinical information was gathered and blood was tested for HLA-CeD. The control group was made up of unrelated Valencian organ donors.RESULTS1034 subjects were analyzed: 457 IBD [207 ulcerative coliti(UC) and 250 Crohn's disease(CD)] patients and 577 healthy controls. 39% of the controls and 34% of the patients had HLA-Ce D(P = 0.0852). HLA-DQ2 was less frequent in UC patients(P = 0.0287), and HLA-DQ8 in CD(P = 0.0217). In women with UC, the frequency of DQ2.5 cis(DQB1*02:01-DQA1*05:01) was reduced ≥ 50% [P = 0.0344; preventive fraction(PF) = 13%]. PFs(7%-14%) were obtained with all HLACe D haplotypes. HLA DQB1*02:02-DQA1*02:01(HLADQ2.2) was more frequent in CD patients with respect to controls(P = 0.001) and UC patients(etiological fraction = 15%).CONCLUSION HLA-CeD is not more frequent in IBD patients, with an even lower frequency of HLA-DQ2 and-DQ8 in UC and CD respectively. HLA-DQ2.5 confers protection from the development of UC, especially in women, and HLADQ8 does so for the appearance of CD. HLA-DQ2.2 is present in 34% of the CD patients and may constitute a genetic risk factor for CD development.     

Updates in therapeutic drug monitoring in inflammatory bowel disease

Biologics and immunomodulators (IMM) are generally considered the most effective therapies for the treatment of ulcerative colitis and Crohn’s disease. However, despite the efficacy of these therapies, many patients either have a primary lack of response or a secondary loss of response to these medications. Therapeutic drug monitoring (TDM) is a systematic approach to managing such patients. In this review, we summarize the latest data on TDM, including reactive and proactive TDM, in patients with inflammatory bowel disease on biologics and/or IMM.     

Regional variation of pediatric inflammatory bowel disease in Saudi Arabia: Results from a multicenter study

BACKGROUND Incidence and severity variations of inflammatory bowel disease(IBD)have been reported from Western populations between continents and regions of the same countries.However,no data were available from other countries.AIM To investigate the regional differences in the IBD profiles of pediatric patients from the Kingdom of Saudi Arabia.METHODS Data from a national multicenter IBD study were used.The incidence,time trend,and clinical presentation of Crohn’s disease(CD)and ulcerative colitis(UC)in the Central region(CR),Western region(WR),and Eastern region(ER)were analyzed and compared.Statistical analysis included Poisson regression analysis for incidence variation and Chi-square test for demographic and clinical parameters.A P<0.05 was considered significant.RESULTS The prevalence of positive family history was lower in children with CD from the ER than the CR or the WR.Consanguinity rate was higher in children with CD and UC from the CR and the ER,respectively.The incidences and time trends of CD and UC were not significantly different between regions.In the ER,a significantly higher percentage of children with CD presented with abdominal pain(P<0.001),blood in stools(P=0.048),stricturing or penetrating disease(P=0.029),higher erythrocyte sedimentation rate(P<0.001),higher C-reactive protein(P<0.001),higher anemia(P=0.017),and lower albumin level(P=0.014).For children with UC from the ER,a significantly higher percentage presented with anemia(P=0.006)and a lower percentage with pancolitis(P<0.001).CONCLUSION The most important finding is the identification of significantly more severe presentation of CD in the ER of the Kingdom of Saudi Arabia.Prospective studies are needed to explain such variations.     

Diagnosing inflammatory bowel disease and differentiating it from potential mimics

The initial diagnosis of inflammatory bowel disease (IBD) requires multiple diagnostic modalities; however, endoscopic evaluation as a diagnostic test is considered the gold standard. Endoscopic evaluation includes colonoscopy with ileoscopy, esophagogastroduodenoscopy, enteroscopy, and capsule endoscopy. IBD encompasses Crohn’s disease, ulcerative colitis, and IBD unclassified. Colonoscopy with ileoscopy along with biopsy collection is essential in most IBD cases for diagnosis and to rule out alternative findings that may mimic IBD including ischemia, diverticulitis, segmental colitis associated with diverticulosis, neoplasia, radiation enteritis, and drug-induced colitis. Esophagogastroduodenoscopy, enteroscopy, and capsule endoscopy are used in the initial workup of specific groups of patients with IBD. The role of endoluminal diagnostic studies in the initial diagnosis of IBD is discussed in detail in this article.     

Impact of a medical interview on the decision to switch from originator infliximab to its biosimilar in patients with inflammatory bowel disease

BackgroundTo lighten the burden on health-care spending, switching from the infliximab originator to a biosimilar in patients with inflammatory bowel disease (IBD) is advocated. However, the uptake of biosimilars lacks initiatives aimed at educating patients.AimsTo explore the impact of a gastroenterologist’s interview on IBD patients’ acceptance for switching from infliximab bio-originator Remicade® to its biosimilar CT-P13 Inflectra®.MethodsAfter the interview of 138 included patients, 120 properly responded to a self-administered questionnaire to collect consent about the switch and relevant data. French national IBD patients’ association (Association François Aupetit) provided an information sheet on biosimilars.Results93 (67.0%) out of 138 and 82 (68.3%) out of 120 patients switched treatment. 114 (79.8%) had never heard about biosimilars. Paradoxically, having heard about biosimilars was associated with a poorer chance to switch (Odds Ratio OR [95% CI] = 0.13 [0.02–0.72]). On the contrary, the more satisfied about generics, the more patients accepted the switch (OR [95% CI] = 1.31 [1.01–1.69]). There were 1.47 (Relative Risk RR [95% CI] = 1.47 [1.07–2.01]) times more chance to agree to the switch if the interview modified the patient’s opinion on biosimilars.ConclusionThis study confirms that an organized information provided to the patient is a contributive way to enhance patient’s acceptance of biosimilars in IBD.     

Sexual health and fertility for individuals with inflammatory bowel disease

The impact of a chronic disease such as inflammatory bowel disease(IBD) on sexual functioning and body image can significantly impair the quality of life of patients. This review considers the sexual and fertility aspects of IBD patients and their daily management. Modern IBD healthcare management should include appropriate communication on sexuality and consider psychological,physiological, and biological issues. Patients with IBD have less children than the general population, and voluntary childlessness is frequent. The most influential factors reported by IBD patients who experience fertility alteration are psychological and surgery-related problems. Pregnancy is a major concern for patients, and any pregnancy for IBD patients should be closely followed-up to keep the chronic disease in a quiescent state. Preconceptional consultation is of great help.     

Impact of the COVID-19 pandemic on inflammatory bowel disease patients: A review of the current evidence

Since the initial coronavirus disease 2019 (COVID-19) outbreak in China in December 2019, the infection has now become the biggest medical issue of modern medicine. Two major contributors that amplified the impact of the disease and subsequently increased the burden on health care systems were high mortality among patients with multiple co-morbidities and overcapacity of intensive care units. Within the gastroenterology-related community, particular concern was raised with respect to patients with inflammatory bowel disease (IBD), as those patients are prone to opportunistic infections mainly owing to their immunosuppressive-based therapies. Hence, we sought to summarize current knowledge regarding COVID-19 infection in patients with IBD. Overall, it seems that IBD is not a comorbidity that poses an increased risk for COVID-19 acquisition, except in patients treated with 5-aminosalicylates. Furthermore, outcomes of the infected patients are largely dependent on therapeutic modality by which they are treated, as some worsen the clinical course of COVID-19 infection, whereas others seem to dampen the detrimental effects of COVID-19. Finally, we discussed the present and the future impact of COVID-19 pandemic and concomitantly increased health care burden on IBD-management.     

Selective granulocyte and monocyte apheresis in inflammatory bowel disease: Its past,present and future

The etiology and pathogenesis of inflammatory bowel disease(IBD), including ulcerative colitis and Crohn's disease, are not fully understood so far. Therefore,IBD still remains incurable despite the fact that significant progress has been achieved in recent years in its treatment with innovative medicine. About 20 years ago, selective granulocyte and monocyte apheresis(GMA) was invented in Japan and later approved by the Japanese health authority for IBD treatment.From then on this technique was extensively used for IBD patients in Japan and later in Europe. Clinical trials from Japan and European countries have verified the effectiveness and safety of GMA therapy in patients with IBD. In 2013, GMA therapy was approved by China State Food and Drug Administration for therapeutic use for the Chinese IBD patients. However, GMA therapy has not been extensively used in China, although a few clinical studies also showed that it was effective in clinical and endoscopic induction of remission in Chinese IBD patients with a high safety profile. This article reviews past history, present clinical application as well as the future prospective of GMA therapy for patients with IBD.     

Epidemiology of inflammatory bowel disease in the Republic of San Marino: The “EPIMICI – San Marino” study

Background

The burden of Crohn’s disease (CD) and ulcerative colitis (UC) has never been estimated in the Republic of San Marino, the third smallest nation of the world.

Epidemiology of inflammatory bowel disease in South America: A systematic review

BACKGROUND The worldwide epidemiology of inflammatory bowel disease(IBD) is rapidly changing. Increasing Crohn's disease(CD) and ulcerative colitis(UC) incidence and prevalence have been recorded in developing regions such as Asia, Africa and Eastern Europe where it was previously thought to be uncommon. Whether this is also the case in South America is not well known. Demonstration that developing regions worldwide have increasing IBD incidence would indicate that environmental change plays a significant role in the development of IBD.AIM To report the incidence, prevalence and disease characteristics of CD and UC within the South American continent.METHODS A systematic review was conducted by searching published studies in major international and regional databases(MEDLINE, EMBASE and Scopus) between January 1990 and December 2018. Outcomes considered were incidence,prevalence, phenotype, environmental and genetic factors, ethnicity and gender.A pair of independent reviewers screened and reviewed all identified articles.RESULTS One hundred and sixty two citations were initially retrieved with 18 studies included in this systematic review. The majority of included studies were from Brazil(n =13, 72%). The incidence of UC ranged from 4.3-5.3/100000 personyears whilst the incidence of CD ranged from 0.74-3.5/100000 person-years.Prevalence ranged from 15.0-24.1/100000 inhabitants for UC and from 2.4-14.1/100000 inhabitants for CD. The incidence and prevalence of both UC and CD has increased significantly in Brazil over the past 21 years. Pancolitis was the most common disease distribution in patients with UC whilst colonic involvement was the most common distribution in CD. People residing in urbanareas were at higher risk of developing both CD and UC.CONCLUSION The IBD burden in South America is increasing at a rate possibly even greater than other developing regions around the world. There is a paucity of highquality epidemiological studies and further robust and representative data are required to further explore modifiable risk factors and disease phenotypes.