Effectiveness and Safety of Ustekinumab in Ulcerative Colitis: Real-world Evidence from the ENEIDA Registry

Abstract Background and Aims The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% o…

Alpha-defensins (α-Defs) in Crohn's disease: decrease of ileal α-Def 5 via permanent methylation and increase in plasma α-Def 1-3 concentrations offering biomarker utility.

Summary An impaired expression of α-defensins (α-Defs) in the ileal mucosa and, conversely, increased levels in plasma, have been reported in Crohn's disease (CD). However, the specificity and correlation of these findings with the degree of inflammation are unclear. We aimed to characterize the concentration and utility of ileal and plasma α-Defs in CD and to analyse a potential epigenetic mechanism of α-Def expression. Peripheral blood samples and ileal biopsies were obtained from patients at disease onset (aCD), from those who achieved remission (iCD) and from two control groups (healthy controls and non-CD-aetiology ileitis patients). Plasma α-Defs 1–3 and 4 were detected by enzyme-link…

Telemedicine in Inflammatory Bowel Disease

Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents.

This is the peer reviewed version of the following article: Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents. Journal of Gastroenterology and Hepatology (2020): 29 April, which has been published in final form at https://doi.org/10.1111/jgh.15084. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

A Web-Based Telemanagement System for Patients With Complex Inflammatory Bowel Disease: Protocol for a Randomized Controlled Clinical Trial

Background: Telemedicine has been successfully used to provide inflammatory bowel disease (IBD) patients with health care services remotely via the implementation of information and communications technology, which uses safe and feasible apps that have been well accepted by patients in remission. However, the design of telemedicine apps in this setting involves difficulties that hinder the adherence of patients to the follow-up plans and the efficacy of these systems to improve disease activity and quality of life. Objective: This study aimed to evaluate the development of a Web platform, Telemonitoring of Crohn Disease and Ulcerative Colitis (TECCU), for remote monitoring of patients with …

Identification of Epigenetic Methylation Signatures With Clinical Value in Crohn's Disease.

INTRODUCTION: DNA methylation is an epigenetic mechanism that regulates gene expression and represents an important link between genotype, environment, and disease. It is a reversible and inheritable mechanism that could offer treatment targets. We aimed to assess the methylation changes on specific genes previously associated with Crohn's disease (CD) and to study their possible associations with the pathology. METHODS: We included 103 participants and grouped them into 2 cohorts (a first [n = 31] and a second validation [n = 72] cohort), with active CD (aCD) and inactive CD (iCD) and healthy participants (CTR). DNA was obtained from the peripheral blood and analyzed by the Agena platform.…

Use of telemedicine in inflammatory bowel disease: a real monitoring option?

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic and relapsing disorder characterized by inflammation of the gastrointestinal tract. The natural progression includes periods of flares and remission, requiring continuous and personalized follow-up to achieve long remission and minimize short and long term damage. In fact, IBD patients show significantly higher rates of utilization of healthcare resources than patients with other conditions [1]. It is important to emphasize that 30-45% of adults are nonadherents [2], making these patients five times more likely to suffer relapses and consequently increasing health care costs [3]. …

Tofacitinib in Ulcerative Colitis: Real-world Evidence From the ENEIDA Registry.

Abstract Aim To evaluate the effectiveness and safety of tofacitinib in ulcerative colitis [UC] in real life. Methods Patients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score [PMS]. Short-term response/remission was assessed at Weeks 4, 8, and 16. Results A total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio [OR] = 0].2; 95% confidence interval [CI] = 0].1–0.4) was the only variable …

A Web-Based Telemanagement System for Improving Disease Activity and Quality of Life in Patients With Complex Inflammatory Bowel Disease: Pilot Randomized Controlled Trial.

Background: The reported efficacy of telemedicine in patients with inflammatory bowel disease (IBD) is inconsistent among studies, and data for complex IBD are lacking. Objective: We aimed to evaluate the impact of remote monitoring using a Web system—Telemonitorizacion de la Enfermedad de Crohn y Colitis Ulcerosa or Telemonitoring of Crohn’s Disease and Ulcerative Colitis (TECCU)—as compared to standard care and telephone care on health outcomes and health care in patients with complex IBD. Methods: We performed a 3-arm randomized controlled trial. Adult patients with IBD who received immunosuppressants and biological agents were recruited from the IBD Unit of a tertiary university hospita…

Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn's Disease Recurrence. A GETECCU Randomised Trial.

Background and aims Postoperative recurrence of Crohn's disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting. Methods We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader. Results We recruited 91 patients [median age 35.…

Correlation between fecal calprotectin and inflammation in the surgical specimen of Crohn's disease

Background: An accurate assessment of the inflammatory activity is crucial to establish the most appropriate treatment in Crohn's disease (CD). The present study aimed to evaluate the utility of preoperative fecal calprotectin (FC) measurement in small bowel CD and its relationship with inflammatory activity in surgical pathology specimens. Methods: This was a prospective observational study including all the patients with small bowel CD operated on at our center between March 2011 and September 2013. Preoperative laboratory and stool tests were performed. A meticulous exploration of entire small bowel was performed during surgery, and the resected bowel (or a sample of whole intestinal wal…

Information resources used by patients with inflammatory bowel disease: Satisfaction, expectations and information gaps.

Abstract Background and purpose Information received by IBD patients about their disease is of particular importance. The objective of the study was to determine the information resources these patients used, together with their perceived information gaps and expected preferences. Patients and methods A prospective, observational, cross-sectional study conducted on IBD patients attending 13 Spanish hospitals during 2008. Patients completed a semi-structured 52-question survey. Results Survey was adequately completed by 379 of 385 patients (98%), of whom 57% had Crohn's disease and 43% ulcerative colitis. Mean patient age was 37.9 years (range, 16–76 years). Gastroenterologists were the most…

Quality of life during one year of postoperative prophylactic drug therapy after intestinal resection in Crohn's patients: Results of the APPRECIA trial

Background: In APPRECIA trial, Crohn's disease (CD) patients undergoing intestinal resection were randomized to postoperative adalimumab (ADA) or azathioprine (AZA). Aims: To evaluate health-related quality of life (HRQoL) in APPRECIA trial. Methods: HRQoL was evaluated using disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) and generic European Quality of Life-5 Dimensions (EQ-5D) questionnaires, completed at baseline and at weeks 24 and 52. Results: Sixty-one patients (37 ADA and 24 AZA) had evaluable data for HRQoL. Patients treated with ADA or AZA had significant improvement from baseline to weeks 24 and 52 in SIBDQ-9 and EQ-5D (p < 0.001 and p = 0.006 for all comparisons…

Mitochondrial dysfunction, persistent oxidative damage, and catalase inhibition in immune cells of naïve and treated Crohnʼs disease

Background: Oxidative stress is considered a potential etiological factor for Crohn's disease (CD). We characterized the reactive oxygen species (ROS) generated in immune peripheral cells of CD patients, as well as their antioxidant enzyme status and the presence of oxidative damage. In addition, mitochondrial function (ΔΨm) was analyzed to detect the possible origin of ROS. Methods: Cells were obtained from patients at the onset of disease, prior to any treatment. Experiments were repeated when patients were in clinical remission. A set of experiments was carried out in a group of CD patients in persistent morphological remission. Controls were healthy volunteers who were not receiving any…

Antitumor Necrosis Factor Agents to Treat Endoscopic Postoperative Recurrence of Crohn's Disease: A Nationwide Study With Propensity-Matched Score Analysis

INTRODUCTION: Patients with Crohn's disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR. METHODS: Multicenter, retrospective, study of patients with Crohn's disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a R…

Telemonitoring of Crohn's Disease and Ulcerative Colitis (TECCU): Cost-Effectiveness Analysis.

Background Although electronic health interventions are considered safe and efficient, evidence regarding the cost-effectiveness of telemonitoring in inflammatory bowel disease is lacking. Objective We aimed to evaluate the cost-effectiveness and cost-utility of the Telemonitorización de la Enfermedad de Crohn y Colitis Ulcerosa (Telemonitoring of Crohn’s Disease and Ulcerative Colitis [TECCU]) Web platform (G_TECCU intervention group) for telemonitoring complex inflammatory bowel disease, compared with standard care (G_control) and nurse-assisted telephone care (G_NT intervention group). Methods We analyzed cost-effectiveness from a societal perspective by comparing the 3 follow-up method…

Relevance of dynamic studies with magnetic resonance enterography in Crohn's disease.

A proper quantification of the inflammatory activity in Crohn's disease (CD) lesions is needed to establish the appropriate management for each patient. The aim of this study is to evaluate the inflammatory activity of affected segments in small bowel lesions using dynamic studies of magnetic resonance enterography (MRE) in patients undergoing surgery, and their correlation with the level of inflammation and histological fibrosis of the surgical piece.A prospective, consecutive, observational, clinical study was conducted that included all the patients with small bowel CD that underwent surgery in this center between March 2011 and September 2013. Diagnosis was established according to Lenn…

Study of the Viral and Microbial Communities Associated With Crohn's Disease: A Metagenomic Approach

OBJECTIVES: This study aimed to analyze and compare the diversity and structure of the viral and microbial communities in fecal samples from a control group of healthy volunteers and from patients affected by Crohn's disease (CD). METHODS: Healthy adult controls (n=8) and patients affected by ileocolic CD (n=11) were examined for the viral and microbial communities in their feces and, in one additional case, in the intestinal tissue. Using two different approaches, we compared the viral and microbial communities in several ways: by group (patients vs. controls), entity (viruses vs. bacteria), read assembly (unassembled vs. assembled reads), and methodology (our approach vs. an existing pipe…

P260 Adaptation of TECCU App based on patients’ perceptions for telemonitoring inflammatory bowel disease: A qualitative study using focus groups

Abstract Background Despite the continuous adaptation of eHealth systems for patients with inflammatory bowel disease (IBD), a significant disconnection persists between users and developers. Since non-adherence remains high, it is necessary to better understand the patients’ perspectives on telemonitoring for IBD. The aim of this study was to adapt the TECCU app to the preferences and needs of IBD patients. Methods A qualitative study was carried out using successive focus groups of IBD patients. Meetings were audio-recorded and a thematic analysis approach was employed until data saturation was achieved. The first group included patients who had used the TECCU app in a pilot clinical tria…

Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) y de la Confederación de Asociaciones de Enfermedad de Crohn y Colitis Ulcerosa (ACCU) para el manejo de los aspectos psicológicos en la enfermedad inflamatoria intestinal

Resumen Objetivos Establecer recomendaciones para el manejo de los aspectos psicologicos de los pacientes con enfermedad inflamatoria intestinal (EII). Metodos Se llevo a cabo una reunion con un grupo de expertos en EII formado por medicos, psicologos, enfermeras y representantes de pacientes. Se presentaron resultados de: 1) un grupo focal previo, 2) encuestas a medicos y pacientes y 3) una revision sistematica sobre instrumentos de cribado de ansiedad y depresion. Se realizo una discusion guiada sobre los aspectos psicologicos y emocionales mas importantes en EII, los criterios de derivacion apropiados y situaciones a evitar. Se selecciono el instrumento validado mas aplicable a la practi…

P051 DNA methylation signatures associated with pathogenesis Crohn's disease-related genes

OP29 Tofacitinib in ulcerative colitis: Real-world evidence from Eneida Registry

Abstract Background Our aim was to evaluate the effectiveness and safety of tofacitinib in ulcerative colitis (UC) in real life. Methods Patients from the prospectively maintained ENEIDA registry treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 4, 8 and 16. The last-observation-carried-forward method was used in patients that stopped tofacitinib before the time-points for clinical assessment. Variables associated with short-term remission at week 8 were identified by logistic regression analysis. The cumulative retention rate and the cumulative incidence o…

Different Genetic Expression Profiles of Oxidative Stress and Apoptosis-Related Genes in Crohn's Disease.

&lt;b&gt;&lt;i&gt;Background/Aims:&lt;/i&gt;&lt;/b&gt; Increased oxidative stress and decreased immune cell apoptosis have been reported to be important factors in the pathogenesis of Crohn’s disease (CD). Our aim was to characterize the genetic expression of molecules implicated in the regulation of oxidative stress and apoptosis in peripheral white mononuclear cells of 18 healthy volunteers (controls) and 20 patients at the onset of CD (active CD [aCD]): 10 who achieved remission (inactive CD [iCD]) and 10 who did not present a complete and deep response to treatment (aCD-T). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; mRNA expression was measured by the Agena MassARRAY quantitative ge…

Metagenomic Analysis of Crohn's Disease Patients Identifies Changes in the Virome and Microbiome Related to Disease Status and Therapy, and Detects Potential Interactions and Biomarkers.

Background The aim of this study was to survey the bacterial and viral communities in different types of samples from patients with Crohn's disease (CD) at different stages of the disease to relate their distribution with the origin and progression of this disorder. Methods A total of 42 fecal samples and 15 biopsies from 20 patients with CD and 20 healthy control individuals were collected for bacterial 16S rRNA gene profiling and DNA/RNA virome metagenomic analysis through 454 pyrosequencing. Their composition, abundance, and diversity were analyzed, and comparisons of disease status, patient status, and sample origin were used to determine statistical differences between the groups. Resu…

Telemedicina en el manejo de pacientes con enfermedad inflamatoria intestinal

Inflammatory bowel disease (IBD) is a chronic and relapsing disorder with significant medical, social and financial impacts. IBD patients require continuous follow-up, and healthcare resource use in this context increases over time. In the last decade, telemedicine has influenced the treatment of chronic diseases like IBD via the application of information and communication technologies to provide healthcare services remotely. Telemedicine and its various applications (telemanagement, teleconsulting and tele-education) enable closer follow-up and provide education resources that promote patient empowerment, encouraging treatment optimisation over the entire course of the disease. We describ…

Telemedicine in the treatment of patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic and relapsing disorder with significant medical, social and financial impacts. IBD patients require continuous follow-up, and healthcare resource use in this context increases over time. In the last decade, telemedicine has influenced the treatment of chronic diseases like IBD via the application of information and communication technologies to provide healthcare services remotely. Telemedicine and its various applications (telemanagement, teleconsulting and tele-education) enable closer follow-up and provide education resources that promote patient empowerment, encouraging treatment optimisation over the entire course of the disease. We describ…

Adaptation of TECCU App Based on Patients´ Perceptions for the Telemonitoring of Inflammatory Bowel Disease: A Qualitative Study Using Focus Groups

Background: Despite the continuous adaptation of eHealth systems for patients with inflammatory bowel disease (IBD), a significant disconnection persists between users and developers. Since non-adherence remains high, it is necessary to better understand the patients&rsquo