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Hay una corrección posterior a este artículo: http://hdl.handle.net/10486/701800, Este artículo tiene una primera parte: http://hdl.handle.net/10486/701802, El tratamiento de la reservoritis es un escenario complejo que requiere una estrecha colaboración médico-quirúrgica. El tratamiento de elección de la reservoritis aguda es el ciprofloxacino o el metronidazol. Ante un primer episodio de reservoritis se recomienda la profilaxis de recidiva con una mezcla de probióticos; sin embargo, no está tan clara su utilidad como profilaxis primaria para prevenir un primer episodio de reservoritis tras la cirugía. El tratamiento de la reservoritis crónica refractaria debe iniciarse con una combinación de antibióticos, y si esta fracasa el siguiente escalón terapéutico es la budesonida oral. Algunas formas refractarias necesitarán terapias biológicas, siendo los anti-TNF α la primera opción, reservándose otros biológicos para pacientes refractarios. La ileostomía definitiva puede ser una opción final en los pacientes más graves, Pouchitis treatment is a complex entity that requires a close medical and surgical relationship. The elective treatment for acute pouchitis is antibiotics. After a first episode of pouchitis it is recommended prophylaxis therapy with a probiotic mix, nevertheless it is not clear the use of this formulation for preventing a first episode of pouchitis after surgery. First-line treatment for chronic pouchitis is an antibiotic combination. The next step in treatment should be oral budesonide. Selected cases of severe, chronic refractory pouchitis may benefit from biologic agents, and anti-TNF α should be recommended as the first option, leaving the new biologicals for multi-refractory patients. Permanent ileostomy may be an option in severe refractory cases to medical treatment

Pouchitis treatment is a complex entity that requires a close medical and surgical relationship. The elective treatment for acute pouchitis is antibiotics. After a first episode of pouchitis it is recommended prophylaxis therapy with a probiotic mix, nevertheless it is not clear the use of this formulation for preventing a first episode of pouchitis after surgery. First-line treatment for chronic pouchitis is an antibiotic combination. The next step in treatment should be oral budesonide. Selected cases of severe, chronic refractory pouchitis may benefit from biologic agents, and anti-TNF α should be recommended as the first option, leaving the new biologicals for multi-refractory patients. Permanent ileostomy may be an option in severe refractory cases to medical treatment.

Resumen Aunque un elevado porcentaje de pacientes con colitis ulcerosa deberia recibir tratamiento topico por via rectal, los estudios de practica clinica han demostrado que este esta infrautilizado. El proposito de este articulo es el de responder a 10 preguntas concretas sobre que farmacos estan disponibles para uso topico, su forma de presentacion, formulacion y metodos de aplicacion, asi como cual de ellos es mas eficaz e idoneo en los distintos escenarios clinicos de la colitis ulcerosa. Asimismo, se evalua la posibilidad de combinar diferentes formulaciones y vias de administracion, y la utilidad en la fase de remision de la enfermedad. Por ultimo, se hacen una serie de recomendaciones para una mejor informacion de los pacientes acerca de una correcta aplicacion y administracion.

Background and aims Crohn’s disease [CD] can develop penetrating complications at any time during the disease course. Enterocutaneous fistulae [ECF] are disease-related complications with an important impact on quality of life. Our aim was to describe the outcomes of this complication, including its medical and/or surgical management and their temporal trends. The primary endpoint was fistula closure, defined as the absence of drainage, with no new abscess or surgery, over the preceding 6 months. Methods Clinical information from all adult patients with CD and at least one ECF—excluding perianal fistulae—were identified from the prospectively-maintained ENEIDA registry. All additional information regarding treatment for this complication was retrospectively reviewed. Results A total of 301 ECF in 286 patients [January 1970-September 2020] were analysed out of 30 088 records. These lesions were mostly located in the ileum [67%] and they had a median of one external opening [range 1-10]. After a median follow-up of 146 months (interquartile range [IQR], 69-233), 69% of patients underwent surgery. Fistula closure was achieved in 84%, mostly after surgery, and fistula recurrence was uncommon [13%]. Spontaneous and low-output fistulae were associated with higher closure rates (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.17-1.93, p = 0.001, and HR 1.49, 95% CI 1.07-2.06, p = 0.03, respectively); this was obtained more frequently with medical therapy since biologics have been available. Conclusions ECF complicating CD are rare but entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A significant proportion of patients receiving medical therapy can achieve fistula closure.

COVID-19; Immunosuppression; Inflammatory bowel disease COVID-19; Immunosupressió; Malaltia inflamatòria intestinal COVID-19; Inmunosupresión; Enfermedad inflamatoria intestinal (1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case−control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March−July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3−5.9), occupational risk (OR: 2.9; 95%CI: 1.8−4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2−2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09−0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution.

Malaltia de Crohn; Factors predictius; Ustekinumab Enfermedad de Crohn; Factores predictivos; Ustekinumab Crohn’s disease; Predictive factors; Ustekinumab Ustekinumab has shown efficacy in Crohn’s Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients’ data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission. This work was supported by Janssen-Cilag Spain. This sponsor had a partial role in study design, analysis, and interpretation of data.

To analyze knowledge, perceptions, attitude, barriers and facilitators of biosimilars uptake across physicians managing immune diseases and hospital pharmacists.Two structured and closed anonymous online surveys were designed and sent to 41 physicians (rheumatologists, dermatologists, gastroenterologists) and 32 hospital pharmacists. Sociodemographic and clinical practice related variables were collected. We also gathered information about biosimilars knowledge and importance, access, attitude in clinical practice and perceptions, barriers and facilitators to biosimilars uptake. A descriptive analysis was performed.Surveys response rate was 100% (hospital pharmacists) and 96% (physicians). We found certain lack of biosimilars knowledge about key aspects including switching, extrapolation, interchangeability or substitution. There was a great variability in the types and brands of biosimilars depending on the hospital. We observed several organization preferences, policies, and practices regarding biosimilars. General perception and attitude to biosimilars was positive. If used, biosimilars were predominantly prescribed in biologic treatment-naive patients (this indication was considered adequate and participants felt comfortable with it). Reluctance to switch in clinical practice was common. The main barriers to biosimilars uptake were the lack of confidence and knowledge. The main facilitators were the development of recommendations from professional associations and societies and the demonstration of interchangeability efficacy. We gathered concerns about biosimilar long term efficacy and safety, lack of real-life data, lack of biosimilars traceability or the risk of biologic reference medicines stock shortages.Biosimilar education and more evidence filling current gaps might help increase prescriber knowledge, comfort and use of biosimilars.Objetivo: Analizar el conocimiento, las percepciones, la actitud, las barreras y los facilitadores sobre el uso de los biosimilares entre los médicos que manejan enfermedades inmunológicas y los farmacéuticos de hospital.Método: Se diseñaron dos encuestas online anónimas, estructuradas y cerradas que se enviaron a 41 médicos (reumatólogos, dermatólogos y gastroenterólogos) y 32 farmacéuticos de hospital. Se recogieron variables sociodemográficas y relacionadas con la práctica clínica. También información sobre el nivel de conocimiento e importancia de los biosimilares, el acceso a los mismos, la actitud en la práctica clínica, y las percepciones, barreras y facilitadores con el uso de los mismos. Se realizó un análisis descriptivo.Resultados: La tasa de respuesta fue del 100% (farmacéuticos de hospital) y del 96% (médicos). Encontramos cierta falta de conocimiento sobre los biosimilares en aspectos clave como el cambio de un biológico de referencia a un biosimilar, la extrapolación de indicaciones, la intercambiabilidad o la sustitución. Hubo una gran variabilidad en los tipos y marcas comerciales de biosimilares entre hospitales. Observamos distintas preferencias, políticas y prácticas en los hospitales en relación con el uso de biosimilares. La percepción y actitud general hacia los biosimilares fue positiva. Los biosimilares se prescribían predominantemente en pacientes sin tratamiento bioló gico previo (esta indicación se consideraba adecuada y los participantes se sentían cómodos con ella). La reticencia al cambio en la práctica clínica fue común. Los principales obstáculos para el uso de biosimilares fueron la falta de confianza y de conocimientos. Los principales facilitadores el desarrollo de recomendaciones de asociaciones y sociedades científicas y la demostración de la eficacia de la intercambiabilidad. Se recogieron preocupaciones sobre la eficacia y seguridad a largo plazo de los biosimilares, la falta de datos en vida real, la falta de trazabilidad de los biosimilares o el riesgo de escasez de existencias de medicamentos biológicos de referencia.Conclusiones: Actividades formativas en biosimilares y una mayor evidencia podrían ayudar a aumentar el conocimiento, comodidad y el uso de los biosimilares por parte de los prescriptores.

The chronic inflammatory process that characterizes inflammatory bowel diseases (IBD) is mainly driven by T-cell response to microbial and environmental antigens. Psychological stress is a potential trigger of clinical flares of IBD, and sphingosine-1-phosphate (S1P) is involved in T-cell recruitment. Hence, stress impact and the absence of sphingosine kinase 2 (Sphk2), an enzyme of S1P metabolism, were evaluated in the colon of mice after sub-chronic stress exposure. Here, we show that sub-chronic stress increased S1P in the mouse colon, possibly due to a decrease in its degradation enzymes and Sphk2. S1P accumulation could lead to inflammation and immune dysregulation reflected by upregulation of toll-like receptor 4 (TLR4) pathway, inhibition of anti-inflammatory mechanisms, cytokine-expression profile towards a T-helper lymphocyte 17 (Th17) polarization, plasmacytosis, decrease in IgA+ lymphoid lineage cells (CD45+)/B cells/plasmablasts, and increase in IgM+ B cells. Stress also enhanced intestinal permeability. Sphk2 knockout mice presented a cytokine-expression profile towards a boosted Th17 response, lower expression of claudin 3,4,7,8, and structural abnormalities in the colon. Intestinal pathophysiology should consider stress and S1P as modulators of the immune response. S1P-based drugs, including Sphk2 potentiation, represent a promising approach to treat IBD.

Background Severe haemorrhage is an uncommon but life-threatening complication of ulcerative colitis (UC). Superselective transcatheter embolization has shown to be an effective and safe therapeutic modality in patients with lower gastrointestinal bleeding of various aetiologies; nevertheless, its role in UC-related acute bleeding is unknown. Cases presentation Efficacy and safety of selective transcatheter arterial embolization in three consecutive UC patients diagnosed with massive haemorrhage admitted in a tertiary institution are reported. In all patients computed tomography scan showed active arterial haemorrhage from ascendant or sigmoid colon; subsequent arteriography demonstrated active arterial bleeding from colic branches of the superior or inferior mesenteric arteries, and selective transcatheter embolization was performed with immediate technical success in all three cases. Nevertheless, rebleeding requiring subtotal colectomy occurred between 5 h and 6 days after the procedure. Conclusions Transcatheter arterial embolization is not an effective therapeutic approach in UC patients with severe, acute colonic haemorrhage. Colectomy should not be delayed in this setting.

Altres ajuts: Takeda Farmacéutica España S.A. Background: Anti-TNFα represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs. Aims: To assess the treatment patterns with the first anti-TNFα in IBD. Methods: Retrospective, observational study. Results: 310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC. Conclusions: Around one-third of IBD biologic-naive patients treated with an anti-TNFα required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNFα due to inappropriate disease control.

Aim To assess the experience with health care among patients with type 2 diabetes (T2DM) and to evaluate patients’ demographic variables and healthcare‐related characteristics which may affect their experience. Methods A cross‐sectional survey was delivered to T2DM adults. Patient experiences were assessed with the ‘Instrument for Evaluation of the Experience of Chronic Patients’ (IEXPAC) questionnaire, a validated 12‐item survey, which describes patient experience within the last 6 months (items 1–11) and hospitalization in the last 3 years (item 12), with possible scores ranging from 0 (worst) to 10 (best experience). Results A total of 451 T2DM patients responded to the survey (response rate 72.3%; mean age 69.5 ± 10.1 years, 67.8% men). The mean overall IEXPAC score was 5.92 ± 1.80. Mean scores were higher for productive interactions (7.92 ± 2.15) and self‐management (7.08 ± 2.27) than for new relational model (1.72 ± 2.01). Only 32.8% of patients who had been hospitalized in the past 3 years reported having received a follow‐up call or visit after discharge. Multivariate analyses identified that regular follow‐up by the same physician and follow‐up by a nurse were associated with a better patient experience. Continuity of healthcare score was higher only in those patients requiring help from others. Conclusions The areas of T2DM care which may need to be addressed to ensure better patient experience are use of the Internet, new technologies and social resources for patient information and interaction with healthcare professionals, closer follow‐up after hospitalization, and a comprehensive multidisciplinary approach with regular follow‐up by the same physician and a nurse., Improving healthcare experience among patients with chronic conditions (eg type 2 diabetes [T2DM]) may be considered a therapeutic goal as it is associated with better clinical effectiveness and safety.Using the IEXPAC tool in 451 patients with T2DM, we identified positive aspects of patient experience, regarding productive interactions, and self‐management score, but not for the new relational model. Being followed regularly by the same physician and receiving additional follow‐up by a nurse were associated with a better experience.Improvement areas of T2DM care to ensure better patient experience may include the use of the internet, new technologies and social resources for patient information and interaction with healthcare professionals, closer follow‐up after hospitalization, and a comprehensive multidisciplinary approach with regular follow‐up by the same physician and a nurse.

Luis Cea-Calvo,1 Ignacio Marín-Jiménez,2 Javier de Toro,3 María J Fuster-RuizdeApodaca,4,5 Gonzalo Fernández,1 Nuria Sánchez-Vega,1 Domingo Orozco-Beltrán6 1Medical Affairs Department, MSD Spain, Madrid, Spain; 2IBD Unit, Gastroenterology Department, Clinical Research Institute Gregorio Marañón (IiSGM), Gregorio Marañón University Hospital, Madrid, Spain; 3Rheumatology Department, A Coruña University Hospital, A Coruña, Spain; 4SEISIDA (Spanish AIDS Multidisciplinary Society), Madrid, Spain; 5Department of Social and Organizational Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain; 6Clinical Medicine Department, Miguel Hernandez University, San Juan de Alicante, SpainCorrespondence: Luis Cea-CalvoMedical Affairs Department, MSD Spain, Josefa Valcárcel 38, Madrid 28027, SpainTel +34 913210740Email luis.cea@merck.comPurpose: To investigate relationships between intentional and non-intentional non-adherence behaviors and patient experience with healthcare and beliefs in medications.Patients and Methods: This is a post hoc analysis of a cross-sectional anonymous survey distributed between May and September 2017 to patients with rheumatic disease, inflammatory bowel disease, HIV infection or diabetes mellitus from outpatient and primary care clinics in Spain. Patients answered five questions about non-adherence behaviors and completed questionnaires on their experience with healthcare (IEXPAC: Instrument to Evaluate the EXperience of PAtients with Chronic diseases) and beliefs about medicines (BMQ: Beliefs About Medicines Questionnaire).Results: Among 1530 respondents, 53% showed ≥ 1 non-adherence behavior; 35% had ≥ 1 non-intentional non-adherence behavior, and 33% had ≥ 1 intentional non-adherence behavior. Patients with HIV infection had the lowest frequency of intentional non-adherence behaviors. Non-intentional non-adherence was associated with patient beliefs (inversely with BMQ overall score) and patient experiences (inversely with IEXPAC Factor 3 sub-score, self-management). Intentional non-adherence was strongly associated with beliefs scores (directly with BMQ concerns and inversely with BMQ necessity sub-score) and inversely associated with HIV infection.Conclusion: The different associations of intentional and non-intentional non-adherence behaviors found in this study help to understand how patient experiences and beliefs influence medical non-adherence, and in the development of strategies for reducing non-adherence.Keywords: BMQ, chronic disease, IEXPAC, intentional behavior, medication adherence, patient beliefs

Purpose: biosimilar infliximab (CTP-13) has been recently approved for the treatment of several immune-mediated inflammatory disorders, including inflammatory bowel disease (IBD). Comparative studies between this biosimilar and original infliximab in the real clinical practice are scarce. The objective of this study was to compare short and long-term safety and efficacy of original (O) and biosimilar infliximab (B-IFX) in biologic-naive, IBD patients in the real life clinical practice. Methods: a retrospective, multicentric study was performed in five Spanish hospitals. Consecutive IBD, biologic-naive patients from an historic cohort who initiated O-IFX from January 2013 were compared with biologic-naive patients, who started treatment with B-IFX since its approval in January 2015. The evaluation of efficacy was assessed after the induction phase, at week 14 and week 54 of treatment. Time to dose escalation or treatment persistence of both O-IFX and B-IFX was also considered. The appearance of serious adverse events was recorded. Results: two hundred and thirty-nine IBD biologic-naive patients who started with O-IFX or B-IFX were included: 153 patients were diagnosed with Crohn’s disease (95 treated with O- and 58 treated with B-IFX) and 86 with ulcerative colitis (40 received O- and 46 received B-IFX). At weeks 14 and 54, both O-IFX and B-IFX groups reached a similar clinical response and remission rates. Time to dose escalation, treatment persistence and safety profile were comparable between both groups. Conclusions: this long-term real-life experience provides additional evidence of the similarity of O- and B-IFX CTP-13 in terms of efficacy and safety in IBD patients.

ObjectiveTo evaluate the impact of comorbidities and extraintestinal manifestations of inflammatory bowel disease on the response of patients with inflammatory bowel disease to antitumour necrosis factor alpha (anti-TNFα) therapy.DesignData from 310 patients (194 with Crohn’s disease and 116 with ulcerative colitis) treated consecutively with the first anti-TNFα in 24 Spanish hospitals were retrospectively analysed. Univariate and multivariate logistic regression analyses were performed to assess the associations between inflammatory bowel disease comorbidities and extraintestinal manifestations with anti-TNFα treatment outcomes. Key clinical features, such as type of inflammatory bowel disease and concomitant treatments, were included as fixed factors in the model.ResultsMultivariate logistic regression analyses (OR, 95% CI) showed that chronic obstructive pulmonary disease (2.67, 1.33 to 5.35) and hepato-pancreato-biliary diseases (1.87, 1.48 to 2.36) were significantly associated with primary non-response to anti-TNFα, as was the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn’s disease). It was also found that myocardial infarction (3.30, 1.48 to 7.35) and skin disease (2.73, 1.42 to 5.25) were significantly associated with loss of response, along with the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn’s disease).ConclusionsOur results suggest that the presence of some comorbidities in patients with inflammatory bowel disease, such as chronic obstructive pulmonary disease and myocardial infarction, and of certain extraintestinal manifestations of inflammatory bowel disease, such as hepato-pancreato-biliary conditions and skin diseases, appear to be related to failure to anti-TNFα treatment. Therefore, their presence should be considered when choosing a treatment.Trial registration numberNCT02861118.

Aims The aims of this study were (a) to know the kinetics of antitumor necrosis factor (TNF) drug serum levels during the induction phase in patients with Crohn's disease; (b) to identify variables associated with these levels; and (c) to assess the relation between these levels and short-term effectiveness in Crohn's disease patients. Methods Patients with Crohn's disease naive to anti-TNF treatment were prospectively included. Remission was defined as a Crohn's disease activity index (CDAI) score 150 at study entry. At week 14, 52 out of 71 patients with CDAI > 150 at baseline (73%) had clinical remission. There were no differences in infliximab levels between patients with and without remission (8 vs. 9.1 mu g/mL, P > 0.05) or with and without response (7 vs. 11 mu g/mL, P > 0.05) at week 14. There was a trend to higher levels of adalimumab concentration in responders in comparison with nonresponders (13 vs. 6.7 mu g/mL, P = 0.05) and in patients who achieved remission in comparison with nonremitters (13.5 vs. 8.4 mu g/mL, P = 0.06). In the multivariate analysis, no variable was predictive of short-term remission, including infliximab and adalimumab serum levels. Conclusion Determining anti-TNF serum levels during the induction phase is not useful for predicting short-term remission in patients with Crohn's disease.

The Th17 immune response plays a key role in autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). Expression of Th17-related genes in inflamed tissues has been reported in autoimmune diseases. However, values are frequently obtained using invasive methods. We aimed to identify biomarkers of MS in an accessible sample, such as blood, by quantifying the relative expression of 91 Th17-related genes in CD4+ T lymphocytes from patients with MS during a relapse or during a remitting phase. We also compared our findings with those of healthy controls. After confirmation in a validation cohort, expression of SMAD7 and S1PR1 mRNAs was decreased in remitting disease (&ndash, 2.3-fold and &ndash, 1.3-fold, respectively) and relapsing disease (&ndash, 2.2-fold and &ndash, 1.3-fold, respectively). No differential expression was observed for other SMAD7-related genes, namely, SMAD2, SMAD3, and SMAD4. Under-regulation of SMAD7 and S1PR1 was also observed in another autoimmune disease, Crohn&rsquo, s disease (CD) (&minus, 4.6-fold, -1.6-fold, respectively), suggesting the presence of common markers for autoimmune diseases. In addition, expression of TNF, SMAD2, SMAD3, and SMAD4 were also decreased in CD (&ndash, 2.2-fold, &ndash, 1.4-fold, &ndash, 1.6-fold, and &ndash, 1.6-fold, respectively). Our study suggests that expression of SMAD7 and S1PR1 mRNA in blood samples are markers for MS and CD, and TNF, SMAD2, SMAD3, and SMAD4 for CD. These genes could prove useful as markers of autoimmune diseases, thus obviating the need for invasive methods.

The Th17 immune response plays a key role in autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). Expression of Th17-related genes in inflamed tissues has been reported in autoimmune diseases. However, values are frequently obtained using invasive methods. We aimed to identify biomarkers of MS in an accessible sample, such as blood, by quantifying the relative expression of 91 Th17-related genes in CD4+ T lymphocytes from patients with MS during a relapse or during a remitting phase. We also compared our findings with those of healthy controls. After confirmation in a validation cohort, expression of SMAD7 and S1PR1 mRNAs was decreased in remitting disease (–2.3-fold and –1.3-fold, respectively) and relapsing disease (–2.2-fold and –1.3-fold, respectively). No differential expression was observed for other SMAD7-related genes, namely, SMAD2, SMAD3, and SMAD4. Under-regulation of SMAD7 and S1PR1 was also observed in another autoimmune disease, Crohn’s disease (CD) (−4.6-fold, -1.6-fold, respectively), suggesting the presence of common markers for autoimmune diseases. In addition, expression of TNF, SMAD2, SMAD3, and SMAD4 were also decreased in CD (–2.2-fold, –1.4-fold, –1.6-fold, and –1.6-fold, respectively). Our study suggests that expression of SMAD7 and S1PR1 mRNA in blood samples are markers for MS and CD, and TNF, SMAD2, SMAD3, and SMAD4 for CD. These genes could prove useful as markers of autoimmune diseases, thus obviating the need for invasive methods.

Aim To assess the likelihood of detecting latent tuberculosis infection [LTBI] by the positive conversion of a serial tuberculin skin test [TST] at 1 year in inflammatory bowel disease [IBD] patients with negative baseline two-step TST. Methods In this multicentre prospective cohort study, we evaluated rate and predictors of conversion of TST at 1 year in patients with negative baseline TST. We also evaluated management of patients who had a positive TST at baseline or a conversion at 1 year. In all patients we assessed TB cases occurring during follow-up. Results Of the 192 IBD patients receiving anti-tumour necrosis factor [TNF] and 220 IBD controls not receiving anti-TNF, 35 [8.5%, 95% CI 5.7-11.3] had positive conversion (median TST induration 13 mm, interquartile range [IQR] 9-16). Ten anti-TNF cohort patients [5.2%, 95% CI 2.5-9.5] versus 25 controls [11.4%, 95% CI 7.5-16.3] had TST conversion [p = 0.029]. In multivariate analysis, conversion was associated with smoking habit (odds ratio [OR] 2.19, 95% CI 1.08-3.97; p = 0.028). Anti-TNF-treated patients had a lower conversion rate [OR 0.41, 95% CI 0.20-0.83; p = 0.013]. The likelihood of conversion correlates with fewer immunosuppressive therapies between baseline TST and TST at 1 year [p = 0.042]. One case of active TB [isoniazid-resistant strain] occurred in a patient with positive baseline TST receiving anti-TNF [0.05 events/100 patient-years]. Conclusions Serial TST at 1 year can detect LTBI in IBD patients receiving anti-TNF therapy with negative baseline TST. Serial TST seems to be advisable to reduce the risk of TB cases associated with inability to detect LTBI in pre-treatment screening.

Background Previous studies comparing inflammatory bowel disease(IBD) features between migrant and native patients have shown clinical phenotype differences. To date, no study has focused on IBD immigrants(MP) in Spain. The aim of this study was to explore the features of MP in Spain and to compare age of disease onset, IBD phenotype and therapeutic requirements with native-born IBD patients(NP). Methods This was an observational, multicentric and case-control study of the nationwide ENEIDA registry. We selected all IBD patients who were born outside of Spain and compared with a control cohort of NP. All included patients were diagnosed with IBD before 2015. Results A total of 13,524 patients were included(1864 MP and 11660 NP).The most prevalent ethnic migrant group was Caucasian(771, 41%), followed by Latin American(572, 31%) and Arabian(341,18%), whereas Asian represented only 6%. Table 1 summarizes the demographic and phenotypic features. 71% of MP were diagnosed with IBD in Spain. There was not a gender predisposition to IBD in the overall migrant group, however more female UC MP were detected compared to UC NP(52 % vs 45%, p Conclusion In the largest cohort of migrant IBD patients in Spain, immigrants were younger, had a shorter disease duration and required a higher use of biologics than natives, pointing phenotypic differences in this population and a universal access to the healthcare system all over the country.

Background Colon immune dysregulation results in a chronic inflammatory response typical of IBD and mainly driven by T-cell response to microbial antigens. Interestingly, stress can trigger or modulate inflammation and even modify the clinical course of IBD. Sphingosine 1-phosphate (S1P) increase in tissues is involved in T-cell recruitment and different compounds acting on S1P signaling are currently under clinical trials to test their ability to impact IBD progression, including sphingosine kinase 2 (Sphk2) inhibitors. Methods Male C57BL/6NJ and Sphk2-/- mice were randomly assigned to 4 experimental groups: Control WT (n=5), Control Sphk2-/- (n=5), Stress WT (n=8), and Stress Sphk2-/- (n=8). A sub-chronic stress mixed model based on immobilization and ultrasound exposure for 2h during 4 days was used. A set of tissue and biochemical assays was performed to evaluate stress and immune responses, S1P pathways, and epithelial barrier integrity. Results Stress caused weight loss and corticosterone upregulation regardless of the genotype. S1P was increased in the colon of stressed mice due to a decrease in its degradation enzymes and Sphk2, leading to an immune dysregulation reflected by an upregulation of TLR4 pathway, an inhibition of anti-inflammatory mechanisms – 15-lipoxygenase, N-formyl-peptide receptor 2 and Liver X Receptor – a decrease in IgA+ and a decrease in IgM+ B-cells and plasmablasts, and a Th17 polarization. Sphk2 deletion did not affect inflammatory processes but could interfere with Th17 response. Moreover, Sphk2-/- mice showed lower expression levels of claudins 3, 4, 5, 7, and 8 that could be related to structural abnormalities relevant to IBD. Stress exposure also decreased some of these claudins and increased intestinal permeability, but a synergistic effect between stress and genotype for permeability was not detected. Conclusion Sub-chronic stress induced colon S1P increase, immune dysregulation and increased intestinal permeability. Sphk2 deletion is involved in structural abnormalities and Th17 response but did not aggravate the inflammatory processes exerted by stress.

Background The information regarding IBD patients with COVID-19 suggests that the factors related to bad outcome are older age and comorbidity whereas immunosuppressants do not have a significant impact worsening the disease evolution. To date, there is no information to assess if there are differences in epidemiological, demographical, and clinical characteristics between infected and non-infected IBD patients. Methods Case-control study in IBD patients with COVID-19 (cases) compared to IBD without COVID-19 (controls) in the period March-July/2020 within the ENEIDA registry (promoted by GETECCU and with more than 60.000 IBD patients included). Cases were matched 1:2 by age (±5y), type of disease (CD/UC), gender, and centre. All controls were selected from only one investigator blind to other clinical characteristics of the patients to avoid selection bias. Results 496 cases and 964 controls from 63 Spanish centres were included. No differences were found within the basal characteristics including CD location, CD behaviour, extraintestinal manifestations, family history of IBD or smoking habits. Cases had ≥ 1 comorbidities (cases:43%vs. controls:36%, p=0.01) and occupational risk (cases:27% vs. controls:10.6%, p Conclusion Comorbidities and epidemiological risk factors are the most relevant aspects for the risk of COVID-19 in IBD patients. This risk of COVID-19 seems to be increased by aminosalicylates but not by immunosuppressants or biologics. The attitude regarding treating IBD patients with aminosalicylates during the COVID-19 pandemic deserves a deeper analysis. Funded by the Carlos III Health Institute COV20/00227.

Background Crohn’s disease (CD) can develop fistulizing complications at any time during the disease course. Enterocutaneous fistulas (ECF) are disabling lesions with a significant impact on quality of life. The aim of this study was to describe the characteristics and natural history of ECF complicating CD, and to analyze its medical and/or surgical management. Methods A retrospective analysis of all adult patients with fistulizing CD with at least one episode of ECF from the ENEIDA registry (over 68,000 patients) was performed. ECF were defined as a communication between the gastrointestinal tract and the skin producing leakage of luminal contents. Additional data describing the ECF and its medical or surgical management were gathered. The main endpoint was any ECF-related surgical intervention. Fistula closure was defined as the absence of drainage, with no new abscess or surgery for at least 6 months. A comparison of the characteristics and outcomes after the availability of biologic agents (Jan/2000) was also performed. The baseline characteristics were analyzed by means of descriptive statistics and were compared by non-parametric tests. Factors associated with surgery were further evaluated in a binary multivariable regression and survival analysis. Results A total of 301 ECF in 286 patients from 46 hospitals diagnosed between Jan/1970-Sept/2020 were included (median age 34 years (IQR, 27–46); 59% male; 67% L3). ECF had a median of 1 external opening (range 1–10), 59% with concomitant internal fistulas, and usually involved the ileum (67%) or colon (23%). After 146 months (IQR, 69–233) of follow-up, 37% received thiopurines, 40% anti-TNF, 6% ustekinumab and 2% vedolizumab. Surgery was performed in 208 patients (69%) after a median of 4 months (IQR, 1.4–12). Fistula closure was achieved in 253 patients (84%) after 30 months (IQR, 4–84), mostly after surgery (54%) and in one third after medical therapy. Fistula recurrence was uncommon (11%) after closure. Patient and fistula characteristics were significantly different after the availability of biologics. In fact, anti-TNF biologics and thiopurines reduced surgery risk (HR 0.5; 0.38–0.67; HR 0.64; 0.47–0.86, respectively). The surgery rate in the biologic era tends to be lower than before (OR 0.63;0.33–1.09) while timing is similar. Closure rates are also comparable, but it was obtained more frequently after medical therapy once biologicals were available (OR 2.21; 1.13–4.29). Conclusion ECF complicating CD entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A number of patients can benefit from medical therapy and achieve fistula closure.

Background The exhaustive registry of COVID-19 cases in patients with IBD is a unique opportunity to learn how to deal with this infection, especially in reference to the management of immunosuppressive treatment, isolation measures or if the disease is more severe in IBD patients due to immunosuppression. With these premises, the aims of this study were to know the incidence and characteristics of COVID-19 in the ENEIDA cohort during the first wave of the pandemic; the outcomes among those under immunosuppressants/biologics for IBD; the risk factors for contracting the infection and poor outcomes; and the impact of the infection after three-month follow-up. Methods Prospective observational cohort study of all IBD patients with COVID-19 included in the ENEIDA registry (with 60.512 patients in that period) between March and July 2020, with at least 3 months of follow-up. Any patient with a confirmed (by PCR or SARS-CoV-2 serology) or probable (suggestive clinical picture) infection was considered as a case. Results A total of 484 patients with COVID-19 from 63 centres were included: 247 Crohn’s disease, 223 ulcerative colitis and 14 unclassified colitis; median age 52 years (IQR: 42–61), 48% women and 44% ≥1 comorbidity. Diagnosis was made by PCR: 63% and serology: 35%. The most frequent symptoms: fever (69%), followed by cough (63%) and asthenia (38%). During lockdown 78% followed strict isolation. 35% required hospital admission (ICU: 2.7%) and 12% fulfilled criteria for SIRS upon admission. 16 patients died from COVID-19 (mortality:3.3%). 12% stop IBD medication during COVID-19. At 3 months, taken into account all included cases, 76% were in remission of IBD. Male gender (OR 1.56; 95%CI:1–2.4, p=0.05), ≥40 years of age (OR 2.55; 95% CI:1.4–4.8; p=0.004), Charlson score ≥1 (OR 2.1; 95% CI:1.3–3.5; p=0.004), and systemic steroids Conclusion IBD does not seem to worsen the prognosis of COVID-19, even when immunosuppressants and biological drugs are used. Age and comorbidity are the most important prognostic factors for more severe COVID-19 in IBD patients. The use of aminosalicylates and the risk of a worse outcome deserves a deeper analysis. Funded by the Carlos III Health Institute (COV20 / 00227).