Environmental Exposure to Trace Elements and Heavy Metals Preceding the Clinical Onset of Inflammatory Bowel Disease.

Background: The immune dysregulation underlying inflammatory bowel disease (IBD) can start years before the diagnosis, but the role of triggering factors and environmental exposures during this period is still uncertain. Methods: This single-center case-control study included asymptomatic subjects with an incidental diagnosis of IBD during the colorectal cancer screening program. Twenty-two minerals and 17 metals were determined at diagnosis in hair samples and compared 1:2 to healthy controls. Results: Six patients with preclinical IBD (3 ulcerative colitis, 67% left-sided; 3 Crohn's disease, 100% ileal, 67% inflammatory behavior) and 13 healthy non-IBD controls were included. No relevant occupational exposures were identified. We found statistically significant higher levels of sodium, potassium, and boron among cases compared to controls; while lower levels of zinc, uranium, copper, and germanium were observed. Conclusions: A range of environmental exposures can be identified during the preclinical phase of IBD, but their relationship with the symptomatic onset and disease progression should be further explored.

Therapeutic drug monitoring in inflammatory bowel diseases. Position statement of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis. / Monitorización terapéutica de los fármacos biológicos en la enfermedad inflamatoria intestinal. Documento de Posicionamiento del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU).

The treatment of inflammatory bowel disease has undergone a significant transformation following the introduction of biologic drugs. Thanks to these drugs, treatment goals have evolved from clinical response and remission to more ambitious objectives, such as endoscopic or radiologic remission. However, even though biologics are highly effective, a significant percentage of patients will not achieve an initial response or may lose it over time. We know that there is a direct relationship between the trough concentrations of the biologic and its therapeutic efficacy, with more demanding therapeutic goals requiring higher drug levels, and inadequate exposure being common. Therapeutic drug monitoring of biologic medications, along with pharmacokinetic models, provides us with the possibility of offering a personalized approach to treatment for patients with IBD. Over the past few years, relevant information has accumulated regarding its utility during or after induction, as well as in the maintenance of biologic treatment, in reactive or proactive strategies, and prior to withdrawal or treatment de-escalation. The aim of this document is to establish recommendations regarding the utility of therapeutic drug monitoring of biologics in patients with inflammatory bowel disease, in different clinical practice scenarios, and to identify areas where its utility is evident, promising, or controversial.

Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry.

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. METHODS: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. RESULTS: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. CONCLUSIONS: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.

Real-world long-term effectiveness of ustekinumab in ulcerative colitis: results from a spanish open-label cohort.

OBJECTIVE: Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients. METHODS: Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented. RESULTS: A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively. CONCLUSIONS: Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients.

Initial management of intraabdominal abscesses and preventive strategies for abscess recurrence in penetrating Crohn's disease: a national multicenter study based on ENEIDA registry.

INTRODUCTION: Intra-abdominal abscesses complicating Crohn's disease (CD) are a challenging situation. Their management, during the hospitalization and after resolution, is still unclear. METHODS: Adult patients with CD complicated with intraabdominal abscess who required hospitalization were included from the prospectively maintained ENEIDA registry from GETECCU. Initial strategy effectiveness and safety to resolve abscess was assessed. Survival analysis was performed to evaluate recurrence risk. Predictive factors associated with resolution were evaluated by multivariate regression and predictive factors associated with recurrence were assessed by Cox regression. RESULTS: 520 patients from 37 Spanish hospitals were included; 322 (63%) were initially treated with antibiotics alone, 128 (26%) with percutaneous drainage, and 54 (17%) with surgical drainage. The size of the abscess was critical to the effectiveness of each treatment. In abscesses < 30mm, the antibiotic was as effective as percutaneous or surgical drainage. However, in larger abscesses, percutaneous or surgical drainage was superior. In abscesses > 50mm, surgery was superior to percutaneous drainage, although it was associated with a higher complication rate. After abscess resolution, luminal resection was associated with a lower 1-year abscess recurrence risk (HR 0.43, 95% CI 0.24-0.76). However, those patients who initiated anti-TNF therapy had a similar recurrence risk whether luminal resection had been performed. CONCLUSIONS: Small abscesses (<30mm) can be managed with antibiotics alone, while larger ones require drainage. Percutaneous drainage will be effective and safer than surgery in many cases. After discharge, anti-TNF therapy reduces abscess recurrence risk in a similar way to bowel resection.

The Risk of Developing Disabling Crohn's Disease: Validation of a Clinical Prediction Rule to Improve Treatment Decision Making.

BACKGROUND: Crohn's disease (CD) is characterized by the development of complications over the course of the disease. It is crucial to identify predictive factors of disabling disease, in order to target patients for early intervention. We evaluated risk factors of disabling CD and developed a prognostic model. METHODS: In total, 511 CD patients were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to identify demographic, clinical, and biological risk factors. A predictive nomogram model was developed in a subgroup of patients with noncomplicated CD (inflammatory pattern and no perianal disease). RESULTS: The rate of disabling CD within 5 years after diagnosis was 74.6%. Disabling disease was associated with gender, location of disease, requirement of steroids for the first flare, and perianal lesions. In the subgroup of patients (310) with noncomplicated CD, the rate of disabling CD was 80%. In the multivariate analysis age at onset <40 years (OR = 3.46, 95% confidence interval [CI] = 1.52-7.90), extensive disease (L3/L4) (OR = 2.67, 95% CI = 1.18-6.06), smoking habit (OR = 2.09, 95% CI = 1.03-4.27), requirement of steroids at the first flare (OR = 2.20, 95% CI = 1.09-4.45), and albumin (OR = 0.59, 95% CI = 0.36-0.96) were associated with development of disabling disease. The developed predictive nomogram based on these factors presented good discrimination, with an area under the receiver operating characteristic curve of 0.723 (95% CI: 0.670-0.830). CONCLUSION: We identified predictive factors of disabling CD and developed an easy-to-use prognostic model that may be used in clinical practice to help identify patients at high risk and address treatment effectively.

[Health-related quality of life by IBDQ-32 in colombian patients with inflammatory bowel disease in remission: A cross-sectional study]. / Calidad de vida relacionada con la salud por IBDQ-32 en pacientes colombianos con enfermedad inflamatoria intestinal en remisión: Un estudio de corte transversal.

In Colombia there are no data about perception of quality of life (QoL) in inflammatory bowel disease (IBD). The aim of this study was to determine the perception of QoL by means of the IBDQ-32 questionnaire in patients with IBD from a sample of patients from different referral centers. We carried out a cross-sectional study in adults with IBD in clinical remission, in outpatient follow-up, in 3 institutions in different cities, between June 2022 and November 2022, eligible subjects were identified, information was collected on different dates, about socio-demographic and clinical aspects, and the IBDQ-32 questionnaire was evaluated on one occasion. Descriptive and analytical analysis of the variables evaluated was performed. 80 patients, 70% women, mean age 38.5(range 18-72; SD 13.25) years. 67.5% ulcerative colitis (UC), 32.5% Crohn's disease (CD). Moderate QoL involvement (median 150 points, interquartile range118.3-181.5) was found in IBD, in UC median 151 (interquartile range120-174.75) points, while in CD 133 (interquartile range106.25-186.25) points. There was greater involvement in the systemic domain, with median 21 (interquartile range 15.8-27) points, and 18.5 (interquartile range 12.8-25.3) points, for UC and CD, respectively. The least affected corresponded to the digestive domain and social function, in median UC 48.5 (interquartile range 40-58.3), and 27(interquartile range 20.8-33); in median CD 43 (interquartile range 35.5-61.75) and 24.5(interquartile range 18-32.5), respectively. No statistically significant differences were found. This study provides unique information about QoL of patients with IBD in Colombia. It is necessary to continue reinforcing the accompaniment, support, and education of patients with IBD.

Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017-2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients' outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

Asociación entre la vitamina D y las enfermedades inflamatorias intestinales

La vitamina D es una hormona conocida desde larga fecha, por sus efectos sobre la salud ósea y la regulación del metabolismo del fósforo y calcio. Desde el descubrimiento de receptores para esta molécula en un gran número de células del organismo, se ha abierto el campo para el estudio de sus efectos sobre el sistema inmune. Sus relaciones con las células del sistema inmune, genes y microbiota hace que el interés sea grande en relación con enfermedades inmunomediadas. Muchos datos indican que esta vitamina tiene efectos preventivos, moduladores y controladores de los efectos adversos de las Enfermedades Inflamatorias Intestinales (EII) en la salud ósea, aunque es difícil demostrar la causalidad de forma taxativa. En esta revisión intentamos resumir la situación actual y los temas de controversia en este interesante campo, centrándonos en las enfermedades inflamatorias intestinales.

Vitamin D is a hormone known for a long time, for its effects on bone health and the regulation of phosphorus and calcium metabolism. Since the discovery of receptors for this molecule in a large number of cells in the body, the field has been opened for the study of its effects on the immune system. Its relationships with the cells of the immune system, genes, and microbiota cause great interest in relation to immune-mediated diseases. Many data indicates that this vitamin has preventive, modulating and controlling effects of the adverse effects of Inflammatory Bowel Diseases (IBD) on bone health, although it is difficult to definitively demonstrate causality. In this review, we try to summarize the current situation and controversial issues in this interesting field, focusing on inflammatory bowel diseases.

Current management of bowel failure due to Crohn's disease in Spain: Results of a GETECCU survey. / Manejo actual del fracaso intestinal por enfermedad de Crohn en nuestro medio: resultados de una encuesta GETECCU.

INTRODUCTION: Intestinal failure is a rare pathology which requires knowledge and highly specialized multidisciplinary management. Crohn's disease (CD) being one of the most frequent causes in adults. MATERIAL AND METHODS: Survey format study carried out within the GETECCU group, included closed format questions about the diagnosis, management and current knowledge of intestinal failure in CD. RESULTS: Forty-nine doctors participated, belonging to different Spanish centers (19 cities). It was considered that a patient suffered from intestinal failure, in 67.3% (33/49 surveyed) when there was a disorder malabsorptive associated regardless of the intestinal length resected, with surgeries resective ileal repeated (40.8%, 20/49), the most frequent cause. It highlights frequent ignorance about the pathology (24.5%) did not know if there were patients in their center and also 40% did not know the pharmacological treatment. A total of 228 patients were registered for follow-up due to intestinal failure of any aetiology, 89 patients (39.5%) were identified with CD. Regarding the therapeutic management of patients with CD and intestinal failure (72.5%) were receiving total parenteral nutrition (NTP) and 24 patients (27%) with teduglutide. Regarding the response to the drug: 37.5% had no response to teduglutide, 37.5% partial response (reduce NTP) and 25% good response (withdrawal of home NTP). In questions related to knowledge about intestinal failure, it was considered limited (53.1%) or very limited (12.2%) by the surveyed. CONCLUSION: It is necessary to carry out a combined management of intestinal failure and CD in the context of a multidisciplinary approach.

Calidad de vida relacionada con la salud por IBDQ-32 en pacientes colombianos con enfermedad inflamatoria intestinal en remisión: Un estudio de corte transversal

En Colombia no hay datos acerca de la percepción de la calidad de vida (CdV) en enfermedad infamatoria intestinal (EII). Se plantea como objetivo determinar la percepción de la CdV mediante el cuestionario IBDQ-32 en pacientes con EII a partir de una muestra de pacientes de diferentes centros de referencia. Se realizó un estudio de corte transversal en adultos, con EII en remisión clínica, en seguimiento ambulatorio, en 3 instituciones en diferentes ciudades, entre junio 2022 a noviembre 2022, se identificaron sujetos elegibles, se recolectó información en fechas distintas, acerca aspectos sociodemográficos y clínicos, se evaluó el cuestionario IBDQ-32 en una ocasión y se realizó análisis descriptivo y analítico de las variables evaluadas. Como resultado, se obtuvieron 80 pacientes, 70% mujeres, edad media 38,5 (rango18-72; SD 13,25) años. 67,5% colitis ulcerosa (CU), 32,5% enfermedad de Crohn (EC). Se encontró compromiso moderado de la CdV (mediana 150 puntos, rango-intercuartílico 118,3-181,5) en EII, en CU mediana 151 (rango-intercuartílico 120-174,75) puntos, mientras en EC 133(rango-intercuartílico 106,25-186,25) puntos. Hubo mayor afección en dominio sistémico, con medianas 21 (rango-intercuartílico 15,8-27) puntos, y 18,5 (rango-intercuartílico 12,8-25,3) puntos, para CU y EC, respectivamente. Y, los menos afectados correspondieron al dominio digestivo y función social, en CU medianas 48,5 (rango-intercuartílico 40-58,3), y 27 (rango-intercuartílico 20,8-33); en EC medianas 43 (rango-intercuartílico 35,5-61,75) y 24,5 (rango-intercuartílico 18-32,5), respectivamente. No se encontraron diferencias estadísticamente significativas. Este estudio aporta información única acerca CdV de los pacientes con EII en Colombia. Se requiere seguir reforzando el acompañamiento, apoyo, y educación a los pacientes con EII.

In Colombia there are no data about perception of quality of life (QoL) in inflammatory bowel disease (IBD). The aim of this study was to determine the perception of QoL by means of the IBDQ-32 questionnaire in patients with IBD from a sample of patients from different referral centers. We carried out a cross-sectional study in adults with IBD in clinical remission, in outpatient follow-up, in 3 institutions in different cities, between June 2022 and November 2022, eligible subjects were identified, information was collected on different dates, about socio-demographic and clinical aspects, and the IBDQ-32 questionnaire was evaluated on one occasion. Descriptive and analytical analysis of the variables evaluated was performed. 80 patients, 70% women, mean age 38.5(range 18-72; SD 13.25) years. 67.5% ulcerative colitis (UC), 32.5% Crohn´s disease (CD). Moderate QoL involvement (median 150 points, interquartile range118.3-181.5) was found in IBD, in UC median 151 (interquartile range120-174.75) points, while in CD 133 (interquartile range106.25-186.25) points. There was greater involvement in the systemic domain, with median 21 (interquartile range 15.8-27) points, and 18.5 (interquartile range 12.8-25.3) points, for UC and CD, respectively. The least affected corresponded to the digestive domain and social function, in median UC 48.5 (interquartile range 40-58.3), and 27(interquartile range 20.8-33); in median CD 43 (interquartile range 35.5-61.75) and 24.5(interquartile range 18-32.5), respectively. No statistically significant differences were found. This study provides unique information about QoL of patients with IBD in Colombia. It is necessary to continue reinforcing the accompaniment, support, and education of patients with IBD.

Epidemiological, Clinical, Patient-Reported and Economic Burden of Inflammatory Bowel Disease (Ulcerative colitis and Crohn's disease) in Spain: A Systematic Review.

INTRODUCTION: This study describes the epidemiological, clinical, patient-reported and economic burden of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), in Spain. METHODS: A systematic review was performed of observational studies reporting the epidemiological, clinical, patient-reported and economic burden of IBD in the Spanish population, from 2011 to 2021. Original articles and conference abstracts published in English or Spanish were eligible. RESULTS: A total of 45 publications were included in the review. The incidence of IBD in adults ranged from 9.6 to 44.3 per 100,000 inhabitants (4.6 to 18.5 for CD and 3.4 to 26.5 for UC). The incidence increased between 1.5- and twofold from 2000 to 2016 (regionally). Up to 6.0% (CD) and 3.0% (UC) IBD-associated mortality was reported. Disease onset predominantly occurs between 30 and 40 years (more delayed for UC than CD). Most frequently reported gastrointestinal manifestations are rectal bleeding in UC and weight loss in CD. Extraintestinal manifestations (EIM) have been described in up to 47.4% of patients with CD and 48.1% of patients with UC. Psychiatric comorbidities were frequently reported in both CD and UC (depression up to 20% and anxiety up to 11%). Reduced health-related quality of life (HRQoL) compared to the general population was reported. Significant symptomatology was associated with high levels of anxiety, depression, stress and lower HRQoL. Main healthcare resources reported were emergency department visits (24.0%), hospitalization (14.7%), surgery (up to 11%) and use of biologics (up to 60%), especially in CD. Direct and indirect annual costs per patient with UC were €1754.1 and €399.3, respectively. CONCLUSION: Patients with CD and UC present a high disease burden which negatively impacts their HRQoL, leading to elevated use of resources.

Spanish Society of Primary Care Physicians (SEMERGEN) and Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) survey on the management of patients with inflammatory bowel disease. / Encuesta Sociedad Española de Médicos de Atención Primaria (SEMERGEN) y Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el manejo de pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Collaboration between Primary Care (PC) and Gastroenterology in inflammatory bowel disease (IBD) is crucial to provide high-quality healthcare. The aim of this study is to analyse the relationship between PC and gastroenterologists at a national level in order to identify areas for improvement in the management of patients with inflammatory bowel disease (IBD) and how to address them, with the aim of subsequently developing concrete proposals and projects between SEMERGEN and GETECCU. METHODS: Descriptive, observational, cross-sectional study, was carried out using an anonymous online questionnaire between October 2021 and March 2022. RESULTS: A total of 157 surveys from Gastroenterology and 222 from PC were collected. 43.8% and 34.3% of gastroenterologists and family practitioners, respectively, considered that there was a good relationship between the units. The level of knowledge from family practitioners regarding different aspects of IBD out of 10 was: clinical 6.67±1.48, diagnosis 6.47±1.46, treatment 5.63±1.51, follow-up 5.53±1.68 and complications 6.05±1.54. The perception of support between both units did not exceed 4.5 on a scale from 0 to 10 in either of the surveys. The most highly voted improvement proposals were better coordination between the units, implementation of IBD units, and nursing collaboration. CONCLUSION: There are deficiencies in the relationship between PC and Gastroenterology with special dedication to IBD that require the efforts of the scientific societies that represent them for greater coordination with the development of joint protocols and agile, fast, and effective communication channels.

Subclinical bowel inflammation increases healthcare resources utilization and steroid use before diagnosis of inflammatory bowel disease.

BACKGROUND: Previous data support that the inflammatory process underlying ulcerative colitis (UC) and Crohn's disease (CD) can start years before the diagnosis. The aim of this study was to determine if patients with an incidental diagnosis of UC or CD demonstrate an increase in healthcare utilization in the years preceding the symptomatic onset of the disease. METHODS: We performed a multicenter, retrospective, hospital-based, case-control study. Patients with an incidental diagnosis of UC or CD during the colorectal cancer screening program at 9 hospitals were included. Cases were matched 1:3 and compared separately with two control populations: one including healthy non-IBD subjects adjusted by gender, age, and date, excluding those with visits to Gastroenterology; and a second control cohort of UC/CD patients with symptomatic onset. RESULTS: A total of 124 patients with preclinical inflammatory bowel disease (IBD) were included (87 UC, 30 CD, 7 IBD unclassified; median age 56 years). Patients with preclinical IBD showed an increase in the number of visits to Primary Care up to 3 and 5 years before diagnosis (aIRR 1.59, 95% CI [1.37-1.86], p = 0.001; aIRR 1.43, 95% CI [1.24-1.67], p = 0.01) and more frequent use of steroids (aOR 2.84, 95% CI [1.21-6.69], p = 0.03; aOR 2.25, 95% CI [1.06-4.79], p = 0.04) compared to matched non-IBD healthy controls, respectively. In contrast, patients with a symptomatic onset visited Primary Care less frequently, but they had an increase in the number of visits to Emergency Department, specialist care, sick-leaves, CT/ultrasound examinations, and use of antibiotics or systemic steroids. CONCLUSIONS: There is an increased need for medical assistance and use of systemic steroids during the presymptomatic phase of IBD. These results will help in establishing new tools for early identification of IBD in the future.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry.

BACKGROUND AND AIMS: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. METHODS: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. RESULTS: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. CONCLUSIONS: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Ileal reservoir-associated complications in ulcerative colitis versus familial adenomatous polyposis: Impact on patient quality of life. / Complicaciones asociadas al reservorio ileal en colitis ulcerativa versus poliposis familiar adenomatosa: Impacto en la calidad de vida del paciente.

BACKGROUND: Proctocolectomy with ileal reservoir is the surgical procedure of choice for patients with ulcerative colitis and familial adenomatous polyposis. OBJECTIVES: To evaluate long-term postoperative complications (1994-2019) in patients operated for familial adenomatous polyposis (FAP) and ulcerative colitis (UC) and the degree of satisfaction with the procedure. METHODS: Observational study based on the analysis of a retrospective database with prospective follow-up in 115 consecutive patients: 79 with UC and 36 with FAP. A total of 88 patients were followed up, 60 with UC and 28 with PFA. RESULTS: 48 males (54.4%) with a mean age of 44.8 ± 10.6 years were evaluated. Indications for surgery were intractable disease in 54 patients (47%), dysplasia/cancer in 43 (37%), severe bleeding in 4 (4%) and perforation in 3 (3%). A proctectomy and mucosectomy of the rectal stump was performed in 67 (76.1%), and a double stapling technique in 21. A protective ileostomy was performed in all patients with UC and FAP. No differences were found in early complications between the two groups. Late complications showed a higher rate of reservoritis in UC patients compared to FAP (44.9 vs. 14.3%, p = 0.001), with more refractory reservoritis in the UC group (13.3 vs. 0%, p = 0.04) with no differences in bowel obstruction, strictures, or anastomotic fistulas. Overall satisfaction and adaptation were considered good in 87% of UC patients and only 57% in the FAP group (p < 0.01). CONCLUSIONS: Proctocolectomy with ileal reservoir has comparable morbidity and mortality, except for the higher rate of reservoritis in patients with a history of UC, despite this contingency there is a better quality of life and greater acceptance of surgery in UC patients than in FAP patients.