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Drug-induced inflammatory bowel disease (IBD) is a clinical entity on the rise due to the frequent use of immunomodulatory therapy. Here we report the case of Crohn's disease due to Ocrelizumab, a humanized anti-CD20 monoclonal antibody approved for the treatment of multiple sclerosis. The exact mechanism by which anti-CD20 antibodies can trigger IBD is unknown, but since IBD and multiple sclerosis are processes included within the spectrum of immunomediated diseases, we could suggest that Ocrelizumab could trigger IBD in genetically predisposed patients.

Recurrent abdominal pain is a common reason for consultation in Gastroenterology. The differential diagnosis includes hereditary angioedema (HAE), a rare disorder characterized by recurrent episodes of angioedema, without urticaria or pruritus, which most often affects the skin, but also mucosal tissues of the gastrointestinal tract, triggered by diverse factors such as infections, trauma, surgery, drugs, or stress. It is a disease with a difficult diagnosis due to its heterogeneous and transitory clinical features, so having a clinical suspicion in the appropriate context would allow the administration of a specific treatment and avoid unnecessary examinations. We present the case of a 19-year-old male followed-up for recurrent abdominal pain that, after numerous microbiological, endoscopic, and radiological examinations, complement tests were requested, obtaining low levels of C4 with increased levels of C1 inhibitor and reduced functional activity, being diagnosed with HAE type II.

Resumen La evidencia de que el seguimiento de las recomendaciones sobre el cribado y tratamiento de la infeccion tuberculosa no evita totalmente la aparicion de tuberculosis en pacientes con enfermedad inflamatoria intestinal, y el uso reciente de nuevos farmacos biologicos y de nuevos inmunomoduladores, ha llevado al Grupo Espanol de Trabajo en Enfermedad de Crohn y en Colitis Ulcerosa a actualizar sus recomendaciones para la prevencion de la tuberculosis en los pacientes con enfermedad inflamatoria intestinal. Se revisan los metodos de diagnostico de la infeccion tuberculosa latente, los distintos escenarios en los que se va a realizar el cribado, las estrategias para disminuir el riesgo de tuberculosis una vez iniciado el tratamiento biologico, las pautas de quimioprofilaxis de la infeccion tuberculosa latente y el manejo de la tuberculosis activa durante el tratamiento biologico. Finalmente, se resumen las recomendaciones en el texto y en un algoritmo.

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.

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.

Vedolizumab is a monoclonal antibody that has demonstrated efficacy and a good safety profile in patients with inflammatory bowel disease. Varicella zoster virus encephalitis is a potentially serious complication not previously described with its use, highlighting the importance of vaccination, as well as early diagnosis and treatment of infections in this type of patients.

BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

Background The management of inflammatory bowel disease (IBD) has substantially changed in the last decades, both in relation to medical and surgical treatments. Aims Principal: To know the rate of surgery in a newly diagnosed IBD cohort within the first year after diagnosis. Secondary: To describe the type of surgeries and indications in this cohort, and to identify predictive factors for surgery (focused on intestinal resection) in these patients. Methods Prospective, population-based nationwide registry. Adult patients diagnosed with IBD -Crohn’s disease (CD) and ulcerative colitis (UC)- during 2017 in Spain were included and were followed-up for 1 year. Kaplan-Meier curves were used to calculate the rate of surgery. In patients with intestinal resections, only medical treatments before surgery were considered. Predictive factors for surgery were identified by Cox-regression analysis. Results 3,454 patients (1,647 CD and 1,807 UC) were included (table 1). The incidence rate for surgery was significantly higher among CD patients (figure 1). A total of 197 patients (6%) underwent surgery within the first 12 months: 126 (64%) intestinal resections, and 71 (36%) perianal surgeries. Fifty-seven percent of intestinal resections were urgent, and 43% elective. The main indications for intestinal resections were: intestinal obstruction in 37%, abscess/fistula in 27%, perforation/acute abdomen in 25%, and refractoriness to medical treatment in 18% of cases. A total of 174 CD patients (10.6%) underwent surgery ¾61% intestinal resections and 39% perianal. Twenty-three UC patients (1.3%) were operated on; the number of surgeries in UC was too low to identify predictive factors. In CD patients, to have been treated with thiopurines [Hazard ratio (HR)=0.2, 95% confidence interval (CI)=0.1–0.3) was associated with lower likelihood of intestinal resection. Disease behaviour at diagnosis [stricturing vs. inflammatory (HR=6.5, 95%CI=4–10) and fistulising vs. inflammatory (HR=13, 95%CI=9–21)] was associated with the risk of intestinal resection. Biologic treatment was not associated with the likelihood of intestinal resection (figure 2). Conclusion Six percent of IBD patients undergo surgery within the first year of diagnosis, being higher in CD (11%) than in UC (1.3%). Sixty percent of intestinal resections are urgent procedures. The risk of surgery is increased in CD patients with fistulising and stricturing behaviour. Thiopurine, but not biologic treatment, is associated with lower risk of surgery.

Background Post-marketing data are required to confirm the durability and the long-term benefit and safety of UST in CD in clinical practice. Our aims were: (1) to evaluate the retention rate of UST in CD patients and to identify predictive factors of UST discontinuation; (2) to assess UST short-term effectiveness; (3) to analyse the durability of the response to UST in the long-term; and (4) to evaluate the safety of UST in clinical practice. Methods Retrospective, multicentre study (>60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) >4)] that received at least one dose of UST intravenously before July 2018 were included. Clinical activity plus biochemical parameters were assessed at every UST administration. Clinical remission was defined as HBI score ≤4, and clinical response as a decrease in HBI ≥3 points. Loss of efficacy was defined as reappearance of symptoms that led to intensify the treatment dose, add another medication to control CD, switching or surgery in patients with short-term remission. The retention rate of UST treatment and the cumulative incidence of loss of efficacy were evaluated by survival curves, and predictive factors were assessed by Cox-regression. The short-term response was evaluated at week 8 and after the induction (week 16). Factors associated with short-term remission were assessed by multivariate analysis. Adverse events were recorded. Data quality was assured by remote monitoring. Results 331 CD patients have been included up to date (Table 1). The incidence rate of UST discontinuation was 15% per patient-year of follow-up: 8%, 13% and 20% at 6, 12 and 18 months (Figure 1). Previous surgery was the only factor associated with a higher risk of UST discontinuation [Hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.1–3.6]. Short-term efficacy is shown in Figure 2. Previous surgery (OR = 0.3, 95% CI = 0.2–0.6) and higher HBI score at baseline (OR = 0.8, 95% CI=0.8–0.9) were associated with an impaired response to UST at week 16. The cumulative incidence of loss of response was 32% per-patient-year of follow-up (Figure 3); A higher HBI score at baseline was associated with a higher risk of losing response (HR = 1.2, 95% CI = 1.1–1.3). Neither the concomitant treatment with immunosuppressants nor the number of previous biologics were associated with UST short- and long-term benefit. Thirty adverse events were reported in 25 (7%) patients (Table 2). Conclusion Sustain is the largest real clinical practice study of UST to treat CD patients with the longest follow-up reported to date. UST was demonstrated to be effective in real-world use in the short and long run. Safety was consistent with the known profile of UST.

There is evidence that following the recommendations on screening and treatment of tuberculosis infection does not completely prevent the onset of tuberculosis in patients with inflammatory bowel disease. This fact, and the increasing use of new biologics and immunomodulators, has led the Spanish Group Working on Crohn's Disease and Ulcerative Colitis to update their recommendations for the prevention of tuberculosis in patients with inflammatory bowel disease. Diagnostic methods for latent tuberculosis infection, different scenarios in which screening is to be performed, strategies to reduce the risk of tuberculosis once biological treatment is initiated and chemoprophylaxis guidelines for latent tuberculosis infection are reviewed, as well as the management of active tuberculosis during biological treatment. Finally, there is a summary of the current recommendations within the paper and in an algorithm. (C) 2020 The Authors. Published by Elsevier Espana, S.L.U.

Supplementary data to this article can be found online at https:// doi.org/10.1016/j.jff.2020.103969., This work supports the massive presence of potential immunomodulatory peptides in the human gut metaproteome. These peptides were identified through the MAHMI database as potentially anti-inflammatory, and sixteen of them synthesized for characterize their mechanism of action. From them, peptide HM14 was encrypted in an extracellular protein produced by Bifidobacterium longum, a common member of the human microbiota, and displayed the highest anti-inflammatory capability. Molecular mechanism of action of HM14 pointed to a specific interaction between this immunomodulatory peptide and antigen presenting cells, which resulted in a higher formation of iTreg cells. Moreover, HM14 was effective in decreasing pro-inflammatory parameters in PBMCs isolated from a cohort of Crohns patients. Finally, non-targeted metabolomics confirmed the ability of HM14 to modulate the metabolic activity of PBMCs to fulfil its energy and biosynthetic requirements. Overall, our combined in silico/multiomics approach supports the human gut metaproteome as a source for immunomodulatory peptides., Our work is supported by the Spanish “Programa Estatal de Investigación. Desarrollo e Innovación Orientada a los Retos de la Sociedad” (grants AGL2013-44761-P and AGL2016-78311-R); the Asociación Española Contra el Cancer (“Obtención de péptidos bioactivos contra el Cáncer Colo-Rectal a partir de secuencias genéticas de microbiomas intestinales”, Grant PS-2016), by the Asturias Regional Plan I + D + i for research groups (FYCYT-IDI/2018/000236) and by the Autonomic “Investigadores Emerxentes do Sistema Universitario de Galicia” (Grant EM2014/046). This work was partially supported by the Consellería de Educación. Universidades e Formación Profesional (Xunta de Galicia) under the scope of the strategic funding of ED431C2018/55-GRC Competitive Reference Group. Finally, the authors wish to thank Jaume Morales and Rubén García form Agilent Technologies for technical support., info:eu-repo/semantics/publishedVersion

Introduction The risk of colon cancer is greater in patients with inflammatory bowel disease (IBD) than in the general population. Chromoendoscopy with dye (CE) is the currently recommended method for detecting dysplasia in screening colonoscopies in IBD patients; however, the role of virtual chromoendoscopy (VC) is not yet well defined. Objective The object of this study was to compare CE and VC with the iSCAN 1 system in the detection of neoplastic lesions in IBD patients. Design We conducted a prospective, single-center, randomized study in IBD patients who underwent a colonoscopy for colon cancer screening. A total of 129 patients were included and were randomized to undergo a CE (n = 67) or a VC (n = 62). The rates of detection of neoplastic lesions by the 2 endoscopic techniques were compared. Results A total of 19 neoplastic lesions (9 adenomas and 10 low-grade dysplasias [LGD]) was detected in 16 patients, 12 lesions in the CE group (17.9%), and 7 lesions in the VC group (11.3%; P = 0.2); no differences were found in the overall rate of detection of lesions (neoplastic or nonneoplastic; P = 1). The median of the total examination time and endoscope withdrawal time (minutes) was significantly lower in the VC group than in the CE group (15 vs 20 and 10 vs 14, respectively; P < 0.001). Conclusion No differences occurred in the rate of detection of neoplastic lesions between CE and VC with iSCAN 1. The time spent on the technique with VC is significantly less than that with CE.

Introduccion y objetivo: la pinza disectora SB Knife™ es un nuevo dispositivo endoscopico que se puede utilizar en el tratamiento del diverticulo de Zenker, pero la experiencia es limitada. Nuestro objetivo fue evaluar la eficacia y seguridad del SB Knife™ en el tratamiento del diverticulo de Zenker. Metodos: estudio unicentrico prospectivo en el que se incluyeron 16 pacientes entre mayo de 2017 y abril de 2019. Se evaluaron las complicaciones del procedimiento y la evolucion clinica. Resultados: la mediana de edad fue de 78 anos y el 62,5% fueron varones. El 100% presentaba disfagia; el 43,8%, atragantamientos; el 31,3%, regurgitacion; y el 6,3%, aspiraciones. La mediana de tamano del diverticulo fue de 20 mm y la mediana de seguimiento, 281 dias. No hubo ninguna complicacion intraprocedimiento y solo una posprocedimiento importante (microperforacion). En todos los pacientes hubo mejoria inicial, pero en dos hubo recurrencia clinica que se trato con el mismo sistema con buen resultado. Conclusiones: el SB Knife™ parece una opcion segura y eficaz en el tratamiento del diverticulo de Zenker.

Background and Aims Although commonly used in inflammatory bowel disease [IBD], thiopurines frequently cause intolerance, and switching to a second thiopurine has only been reported in some small series. Ours aims in this study were to evaluate the safety of switching to a second thiopurine in a large cohort, and to assess the impact of age on tolerance. Methods Adult IBD patients from the ENEIDA registry, who were switched to a second thiopurine due to adverse events [excluding malignancies and infections], were identified. At the beginning of thiopurine treatment, patients were divided by age into two groups: 18–50 and over 60 years of age. The rate and concordance of adverse events between the first and second thiopurines, treatment intolerance, and persistence with the second thiopurine were evaluated. Results A total of 1278 patients [13% over 60 years of age] were switched to a second thiopurine. At 12 months, the cumulative probability of switch intolerance was 43%, and persistence with treatment was 49%. Independent risk factors of switch intolerance were age over 60 years (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.07–2.07; p = 0.017) , previous gastrointestinal toxicity [OR 1.4; 95% CI 1.11–1.78; p = 0.005], previous acute pancreatitis [OR 6.78; 95% CI 2.55–18.05; p Conclusions In a large series in clinical practice, switching to a second thiopurine proved to be a valid strategy. Tight monitoring of elderly IBD patients switching to a second thiopurine because of adverse events is recommended.

Lactobacillus genus includes both probiotic and representative strains of the human gut microbiota. Independent studies have reported on the anti-inflammatory properties of different Lactobacillus strains, although we are far from understanding the underlying molecular interplay. In this work we show that a daily administration of Lactobacillus acidophilus DSM20079T (DSM20079) to healthy piglets resulted in plasmatic increases of the anti-inflammatory IL10, whilst IL12 and the pro-inflammatory ratio IL12+TNF/IL10 decreased. The extracellular protein fraction of DSM20079 was identified as the responsible for the crosstalk interaction that elicited these tolerogenic effects. This strain was able to activate innate immune pathways in dendritic cells and to decrease the production of pro-inflammatory cytokines in both CD4+/CD8+ T cell subsets in healthy donors and in Crohns Disease patients. The tolerogenic effect exerted by the extracellular proteins of this strain suggests their potential use as coadjutant for therapeutic applications targeting chronic inflammatory illnesses., Our work is supported by the Spanish “Programa Estatal de Investigación, Desarrollo e Inovación Orientada a los Retos de la Sociedad” (grant AGL2016-78311-R); the Asociación Española Contra el Cancer (“Obtención de péptidos bioactivos contra el Cáncer ColoRectal a partir de secuencias genéticas de microbiomas intestinales”, Grant PS-2016) and by the Asturias Regional Plan I+D+i for research groups (FYCYT-IDI/2018/000236). This study was also supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER006684). SING group thanks CITI (Centro de Investigación, Transferencia e Innovación) from University of Vigo for hosting its IT infrastructure. LJR was supported by the Principado de Asturias, PCTI 2018–2020 (GRUPIN: IDI2018-000237) and FEDER. This work was partially supported by the Consellería de Educación, Universidades e Formación Profesional (Xunta de Galicia) under the scope of the strategic funding of ED431C2018/55-GRC Competitive Reference Group., info:eu-repo/semantics/publishedVersion

Background The effectiveness of the switch to another anti–tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8–3; P < 0.0001) and ulcerative colitis vs Crohn’s disease (HR, 1.6; 95% CI, 1.1–2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

Background: Idiopathic acute pancreatitis (LAP) in patients with inflammatory bowel disease (IBD) is not well characterized. Our purpose was to better understand this condition and its natural history. Methods: Retrospective cohort study conducted at nine Spanish IBD referral centers. Patients with IBD and a first episode of acute pancreatitis (AP) between 1998 and 2018 were included. Patients with a previous episode of AP or a diagnosis of chronic pancreatitis were excluded. LAP and non-LAP were compared by multivariate logistic regression and survival analysis. Results: We identified 185 patients with IBD (68.7% Crohn's disease) and a first episode of AP. Thirty-eight of those 185 (20.6%) fulfilled criteria for LAP. There were no severe cases of LAP. On multivariate analysis, AP before IBD diagnosis (21.1% vs. 3.4%, p = 0.04) and ulcerative colitis (52.6% vs. 23.1%, p = 0.002) were significantly more common in LAP. Further work-up was performed in 16/38 (42%) LAP patients, and a cause was identified in 6/16 (37.5%). Median time from AP to the end of follow-up was 6.3 years (3.1-10). Five-year risk of AP recurrence was significantly higher in LAP group (28% vs. 5.1%, log-rank p = 0.001), with a median time to first recurrence of 4.4 months (2.9-12.2). Conclusions: LAP represents the second cause of AP in patients with IBD. It is more frequent in ulcerative colitis, and presents a high risk of recurrence. Additional imaging work-up after a first episode of LAP in IBD patients is highly advisable, as it identifies a cause in more than one-third of cases. (C) 2020 LAP and EPC. Published by Elsevier B.V. All rights reserved.

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.

Musculoskeletal symptoms are the most common extraintestinal manifestations of inflammatory bowel disease (IBD). An essential step in the management of these patients is to establish referral algorithms through the use of appropriate screening tools. Our objective was to evaluate the performance of two simple questionnaires to detect inflammatory arthritis (IA) in patients with IBD. Two questionnaires, one for detecting axial IA and the other for peripheral IA, were tested among 112 IBD unselected consecutive patients of both sexes, aged 18–45 years. The study period was from January to December 2016. Each questionnaire was composed of three simple questions. If the patient answered affirmatively at least to two of the three questions, the questionnaire was considered positive. Clinical diagnosis of IA based on an expert’s opinion was the reference gold standard. To obtain a weighted value of sensitivity and specificity, likelihood ratio (LR) values were calculated. Twenty-seven percent of the patients were considered positive responders to the axial questionnaire while 32% were considered positive responders to the peripheral questionnaire. Twenty-four patients (21.4%) were diagnosed with axial IA, whereas 26% had peripheral IA. The axial questionnaire yielded a sensitivity of 87.5% (67.6–97.3), specificity of 89.8% (81.5–92.2) and LR+ of 8.6 (4.5–16.2). For the peripheral questionnaire, these values were 82.8% (64.2–94.2), 87.4% (79–93.3), and 6.6 (3.8–11.4), respectively. Both questionnaires showed an adequate screening capacity for IA in patients with IBD. Their specificity, together with their simplicity, can make them suitable detection tools in gastroenterology and general medicine consultations.

Background A less aggressive phenotype of Crohn’s disease (CD) has been reported in patients with elderly onset CD. Despite this, similar surgical rates among younger and older CD patients have been reported. However, scarce data are available about the risk of postoperative recurrence (POR) regarding the age, and no data are available about the use of immunosuppressants and biological agents for prevention of POR in elderly patients. Our aim was to evaluate the management of CD in the postoperative setting and the rate of surgical POR in CD patients according to the age at surgery. Methods Cohort study including all adult CD patients in the ENEIDA registry (a prospectively-maintained database of the Spanish Working Group in IBD –GETECCU-) who underwent a first intestinal resection with ileo-colonic anastomosis. Patients were grouped regarding their age at the moment of the first surgery: over 60 years (elderly) and between 18 and 60 years of age (controls). Preventive treatment for POR, surgical POR (need for a further intestinal resection) and postoperative morbidity were compared between both groups. Results Out of the 69,740 IBD patients included in the ENEIDA database, 3,982 had a first intestinal resection for Crohn’s disease with an ileo-colonic anastomosis between 2005 and 2020. Of them, 535 were elderly and 3,454 controls. Time from IBD diagnosis to surgery was significantly longer in the elderly (114±128 vs. 93±97 months; p Conclusion The elderly patients show similar rates of surgical POR as compared to younger patients. Given the high risk of thiopurine and anti-TNF-related adverse events, elderly patients with inflammatory pattern would benefit from preventive therapy with safer biologicals.

Background The urinary metabolome of patients with Crohn’s disease (CD) differs significantly from healthy subjects and, among other features, reflects the specific gut dysbiosis affecting these patients. However, most of the studies included established and treated CD patients. Our aim was to characterize the urinary metabolome of onset and treatment-naïve CD patients and to identify the metabolic profile related to the different CD clinical classifications. Methods Patients newly diagnosed with CD (n=131) were prospectively included. Control healthy subjects (HC, n=338) were recruited among the general population and matched for sex, age and BMI to the IBD subjects. Fasting urine was obtained before starting any treatment. Metabolomic analysis was performed by proton nuclear magnetic resonance (1H NMR). We performed a comparative assessment of the urinary metabolome profile using a linear regression model for each metabolite, including sex, age, BMI, and smoking habit as covariates to control for confounding. The different subgroup comparisons within CD were made as follows: (1) CD; (2) CD location (Montreal Classification): L1 (ileal) + L4 (ileal and upper-intestinal), L2 (colonic) and L3 (ileocolonic); (3) endoscopic CD activity: 0, 1, 2 and 3; and (4) CD phenotype: B1 (inflammatory), B2 (stricturing) and B3 (penetrating), versus HC. In addition, data analysis was carried out using partial least squares-discriminate analysis (PLS-DA) to determine class membership based on distinct metabolomic profile. Results The primary characteristics of the CD patients and HC are shown in Table 1. Several metabolites were identified to be differently abundant in each group (Table 2). These metabolites are involved in relevant processes related to energy and aminoacids metabolism, and also include gut-derived metabolites. The PLS-DA model separated patients within the different clinical subgroups (Figures 1–4). Figures 1–4(b) show the main metabolites involved in each group separation. Many of these metabolites are in accordance with the differential metabolites obtained using the univariate analysis (Table 2), showing the potential of this approach to group CD patients and to identify potential biomarkers. Conclusion Analysis of urinary metabolites can help to understand the etiopathological mechanisms in CD. It has the potential to provide a non-invasive means of diagnosing CD, and can differentiate between CD clinical expressions.

Background The prevalence of penetrating disease in Crohn’s disease (CD) increases progressively over time, and evidence on the medical treatment of this complication is limited. The aim of this study was to evaluate the efficacy of biologic agents in CD complicated with internal fistulising disease. Methods A retrospective analysis of all adult patients from the ENEIDA registry (>68,000 patients) with CD who received at least one biologic agent -anti-TNF, ustekinumab or vedolizumab- for penetrating disease was performed. Exclusion criteria comprised treatment for perianal disease, enterocutaneous, anastomotic or periostomal fistula tracts. The main outcomes were fistula-related surgery and fistula closure on cross-sectional imaging. Preestablished secondary outcomes included the rate of abdominal abscess, the need for percutaneous drainage, the changes in the number of fistula tracts, fistula closure rates, and the safety profile.The baseline characteristics were analyzed by means of descriptive statistics and were compared by non-parametric tests. Predictive factors associated with surgery and fistula closure were evaluated by a multivariable logistic regression and survival analyses. Results A total of 710 patients (median age 38 years [IQR, 28-48], 59% male, 55% L3) receiving 791 biologic treatments were included at 53 sites (701 anti-TNF, 71 ustekinumab, and 19 vedolizumab). Patients had a median of 1 (range 1-5) fistula tracts, 49% of them entero-enteric followed by entero-colic (28%). After a median follow-up of 59 months (IQR, 27-105), 244 patients (31%) required surgery due to internal fistulising complications after 8.5 months (IQR, 3-24). Patients with ileocolonic disease (OR 1.99 [1.22-3.23]), entero-urinary fistulas (OR 2.35 [1.17-4.73]), or with a stricture distal to the fistula (OR 2.1 [1.31-3.36]) showed a higher risk of surgery, with no differences between biologic drugs (Figure 1). Combination therapy reduced the risk of surgery (HR 0.58 [0.37-0.90]). Fistula closure was observed in 24% of patients after a median of 15 months (IQR, 7.5-27). Patients with a lower number of fistula tracts showed a higher probability of closure (OR 1.72 [1.09-2.7]). Conclusion A high proportion of patients with internal fistulizing CD benefit from biologic treatment after a median of 5 years. During this follow-up, around two thirds of patients are free of surgery and one in every four patients achieves fistula closure.

Background and Aim In ulcerative colitis (UC), the main goals of treatment are to control disease activity and normalize health-related quality of life (HRQoL). In this study, we explored the relationship between disease activity (measured using the Simple Clinical Colitis Activity Index [SCCAI]) and patient HRQoL (measured using the EuroQoL [EQ]-5D-5L). Methods A total of 199 patients with UC were followed for 6 months. At months 3 and 6, patients completed an online SCCAI. Within 2 days of completing the SCCAI, patients completed an at-clinic EQ-5D-5L questionnaire and the treating gastroenterologist completed the SCCAI. Results A consistent and approximately linear relationship was identified between patient HRQoL and patient-completed and physician-completed SCCAIs. A lower SCCAI score corresponded to a higher EQ-5D-5L index value. Correlation between EQ-5D-5L index values and patient-completed online SCCAIs was moderate (ρ −0.49; P

Background INFEII registry (ClinicalTrials.gov: NCT02904590) is a prospective study promoted by GETECCU to determine the incidence and risk factors of infection in an inception cohort of IBD patients. Despite preventive measures and recommendations of scientific societies, TB remains a problem in patients with IBD treated with immunosuppressants (IMM) and biologics. AIMS To asses: (1) the screening of TB performed at the time of inclusion of a patient in the INFEII registry, (2) the incidence of latent TB; and (3) compliance with national and European recommendations. Methods A longitudinal prospective study of incident cases with IBD, initiated in October 2016 and with a planned follow-up of 5 years. In September 2019, INFEII registry had 1241 patients from 28 centres throughout Spain. The study protocol determines the mandatory fulfilment of TB screening in every patient, leaving to the centre the freedom of decision on what procedures to perform. Guidelines recommend a mandatory study before starting immunosuppression, especially with biological treatment, using the combination of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) or at least one TST with a booster test1,2. Results Of the 1241 patients 233 (19%) had no screening, 494 (40%) had one [TST 158, IGRA 299, thorax-X-ray 37], 288 (23%) two [TST + IGRA 87, IGRA + thorax-X-ray 130, TST + thorax-X-ray 30, TST + booster 41], 128 (10%) three [TST + IGRA + thorax-X-ray 65, TST + booster + IGRA 23, TST + booster + thorax-X-ray 40] and 98 (7.9%) the four tests [TST + booster + IGRA + thorax-X-ray]. 486 patients (48%) receive pharmacological immunosuppression (172 IMMS, 195 biologics, 119 COMBO) and from them 198 (41%) followed the guidelines recommendation (131 TST and IGRA and 118 TST-booster), 245 (50%) had some method for TB screening [TST 43, IGRA 112, thorax-X-ray 15, IGRA + thorax-X-ray 57, TST + thorax-X-ray 18] and 43 patients (8.8%) had no screening. With the baseline screening, latent TB was detected in 134 patients (13%), 63 (47%) receiving anti-TB chemotherapy. In patients initiating immunosuppression, latent TB was detected in 35 cases [of which 28 received prophylaxis but 7 under IMM did not]. Active TB was detected in 4 cases: 2 during baseline screening, one without screening and one with negative screening (negative TST and IGRA, without booster receiving biological treatment). Conclusion Despite TB in IBD is a relevant problem, there is ample room for improvement for the implementation of mandatory minimum screening recommendations, even in prospective protocolised projects. References

Background and Aims Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. Methods PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. Results In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50–139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7–19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9–5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1–9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39–53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. Conclusions PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.

[Background and Aims] To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®., [Methods] Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The ‘switch cohort’ [SC] comprised patients who made the switch from Remicade® to CT-P13, and the ‘non-switch’ cohort [NC] patients remained under Remicade®., [Results] A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2–6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]., [Conclusions] Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe., This research has been funded by grants from the Instituto de Salud Carlos III [PI13/00041 and FI17/00143].