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Background and objective Hypersensitivity reactions to oxaliplatin may affect prognosis by jeopardizing the timely completion of scheduled treatment sessions or by forcing reactive patients into unexpected changes in therapy. Rapid drug desensitization (RDD) enables these patients to receive their first-choice treatments safely. However, the possible effects of RDD on the efficacy of oxaliplatin have never been studied. Objective: The objective of this study was to evaluate the effect of RDD on survival rates in oxaliplatin-hypersensitive patients. Methods We performed a 7-year retrospective study to compare survival between oxaliplatin-hypersensitive cases (patients receiving oxaliplatin by RDD) and nonallergic controls (patients receiving standard oxaliplatin infusions). The primary endpoint of this study was overall survival (OS) in cases and controls (Kaplan-Meier method with log-rank test comparisons). Results OS was 23.7 months (95%CI, 15.3-30.9) for the 67 cases who underwent 337 RDDs, while for controls (n=143), OS was 34.5 months (95%CI, 21.7-55.5). There were no significant differences between the groups (HR, 1.42; 95%CI, 0.93-2.17; P =.104). Conclusions Survival outcomes of oxaliplatin-hypersensitive patients who received oxaliplatin via RDD did not differ significantly from those of control patients who received oxaliplatin via standard administration. Receiving oxaliplatin by means of RDD might be an effective therapeutic alternative for oxaliplatin-hypersensitive patients.

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 Pouchitis and other inflammatory disorders of the pouch (IDP), such as Crohn′s-like disease of the pouch (CDP), are frequent in patients operated for a previous diagnosis of ulcerative colitis. Many different therapies have been used, but the effectiveness of immunosupresants (IMM) has been poorly explored in this setting. Our aim was to evaluate the use, efficacy and safety of IMM in patients with pouchitis or another IDP. Methods Retrospective and multicentric study of a Spanish cohort of pouch-carrying patients with previous diagnosis of ulcerative colitis, and subsequent diagnosis of IDP, following ECCO diagnostic criteria. Patients who used IMM to treat these conditions were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission, and non-response as no improvement or worsening symptoms. Endoscopic response was evaluated when possible using modified pouchitis disease activity index (PDAI) endoscopic subscore. Adverse events were collected. We used descriptive statistics. Results In the overall cohort of 338 patients with IDP, 93 (27%) were treated with IMM. Of those, 57% males, median age 40 (20-71) ys, and 72% non-smokers. Colectomy was performed at a median age of 31 (18-63) ys and IPD was diagnosed 25 (1-235) months after ileostomy closure. IMM used were thiopurines (n=86), methotrexate (n=4), cyclosporine (n=2) and tacrolimus (n=1). IMM were used as monotherapy in 66 (71%) cases and were indicated as treatment of pouchitis (n=60, 65%), CDP (n=32, 34.4%) and cuffitis (n=1, 1%). Effectiveness was evaluated only for thiopurine monotherapy (n=62). After a median follow-up of 23 (1-234) months, clinical remission was achieved in 31%, clinical response in 31% and non-response in 38% (Figure 1). There were no differences in effectiveness between pouchitis and CDP (63.9% vs 57.7%, p= 0.62). Endoscopic response was evaluated in 19 (30.6%) cases. After a median of 9 months of follow-up median PDAI endoscopic subscore dropped from 3 (range 2-4) to 1 (range 0-3), (Figure 2). Adverse events related with treatment appeared in 28 patients (45%). Thiopurines were discontinued in 39 cases (63%) due to failure (17), toxicity (16) and long remission (6 cases). Conclusion In our cohort, thiopurines were used in 27% of patients with IDP, with long-term benefit (remission or response) in around two-thirds of them. This therapy could be one more option to manage these disorders.

Background Pouchitis and Crohn′s-like disease of the pouch (CDP) can be refractory to conventional therapy. Evidence of biological therapy has been rarely reported in large patient cohorts. We explored the use and effectiveness of these therapies and compared the success of a second biologic after antiTNF failure. Methods This is a retrospective RESERVO study of the Spanish cohort of GETECCU, that included patients operated for ulcerative colitis, with pouch construction, and subsequent diagnosis of pouchitis, CDP or cuffitis second ECCO diagnostic criteria1. Patients treated with antiTNF, Vedolizumab and/or Ustekinumab were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission and non-response as no change or worsening of these symptoms. We also compared the effectiveness of second biologic (antiTNF vs vedolizumab-ustekinumab) after antiTNF failure, using descriptive and comparative statistics. Results The cohort comprised 145 patients. Demographic and clinical characteristics are represented in Table 1. A total of 232 biologic therapies were indicated. Of the total cohort, 60 (41.3%), 21 (14.4%) and 6 (4.1%) used two, three and four lines, respectively. Biologics used were Infliximab (n=95), Adalimumab (n=69), Vedolizumab (n=35), Ustekinumab (n=26) and Golimumab (n=7). Therapy characteristics, clinical effectiveness, need for intensification, discontinuation, and therapy duration for each biological therapy are represented in Table 2. Global rates of clinical remission, response, non-response and loss of response to a first biologic were 21.8%, 27.5%, 21.1% and 29.6%. Female gender was the only factor associated with effectiveness to a first biologic in univariate analysis (OR 2.16, CI 1.08–4.32, p 0.027). There were no significant differences regarding efectiveness between type of pouch disorder (pouchitis vs CDP, 51.6 vs 47.6%, p 0.48) or biologic agents. Thirty-nine patients received a second biologic after prior antiTNF failure (28 a second antiTNF and 11 non-antiTNF: 6 Vedolizumab, 5 Ustekinumab). Basal characteristics in this subgroup showed no significant differences. Clinical response (21.4 vs 63.6%, p 0.02) and discontinuation therapy rates (82.2 vs 54.5 %, p 0.04) after 11 months showed a more favorable profile for non-antiTNF therapy. Conclusion Biologics represent an effective option in the management of pouchitis and Crohn′s like disease of the pouch. Despite our small sample size, non-antiTNF therapy could be the best option after antiTNF failure. 1Fernando Magro. J Crohns Colitis 2017; 11(6): 649–670.

Background Adalimumab (ADA) dose escalation from 40 mg SC every other week (EOW) to 40 mg weekly is approved for IBD patients with loss of response. A recently registered device containing 80 mg of ADA will allow an alternative dose escalation regimen with SC doses of 80 mg EOW. The ADASCAL study aimed to evaluate the preferences and satisfaction of patients with modifying the ADA regimen from 40 mg weekly to 80 mg EOW. Methods This multicentre cross-sectional study included patients with IBD in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW according to clinical practice. Patients who have received at least 4 doses of 80 mg EOW completed a 4-item self-questionnaire (a Likert-like 5-point scale for preferences, 2 closed questions for convenience, and a 100-point visual analogue scale [VAS] to evaluate patient’s preference for weekly or EOW ADA) (Figure 1); and the 14-item Treatment Satisfaction Questionnaire for medication (TSQM 1.4) that covers 4 domains: effectiveness, side effects, convenience, and overall satisfaction. Results Seventy-seven patients (64 CD, 13 UC; 67.5% men; mean age 48 years, SD 14.1) were included. The overall mean duration of exposure to ADA was 66 months (SD 34), with mean exposure to ADA 40 mg weekly of 40 months (SD 25), and mean exposure to ADA 80 mg EOW of 12 months (SD 5). At the time of the survey, 87.1% of CD patients and all UC patients were in clinical remission (Harvey-Bradshaw index ≤4 for CD, Partial Mayo score ≤1 for UC). According to the results of the questionnaires, 74% of the patients preferred the 80 mg EOW ADA regimen (59.7% had a strong preference and 14.3% had a slight preference) (Figure 1). Patients referred that ADA EOW regimen interferes less with daily activity and with travel plans. Most patients wanted to continue with ADA 80 mg EOW, as reflected by a mean VAS score of 84.7 (SD 24.1), where 0 indicated a choice for weekly ADA, 100 for ADA EOW, and 50 indifferent. Overall, 77% of patients preferred to continue with ADA EOW, 4% with ADA weekly, and 17% were indifferent. Attending physicians also reported a greater preference for the EOW ADA regimen (mean VAS score 93, SD 7.8). The mean global satisfaction according to the TSQM was 84.3% (SD 13.5), where 0 indicated extremely dissatisfied and 100 extremely satisfied. Patients reported very high TSQM scores for individual components: effectiveness 77.6% (SD 16.9), convenience 83.7% (SD 14.5), and side effects 86.1% (SD 23.4). Conclusion IBD patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW reported a higher preference for the EOW regimen. TSQM results indicated that patients had a high level of satisfaction with the current EOW regimen. Therefore, most patients wanted to continue with ADA 80 mg EOW.

Introducción: Diferentes vacunas frente a SARS-CoV-2 están actualmente en el mercado y se recomiendan en pacientes con Enfermedad Inflamatoria Intestinal (EII). No tenemos suficiente evidencia sobre la aceptación de este tipo de vacunas. El objetivo del estudio fue evaluar la aceptación de la vacuna frente a SARS-CoV-2 por parte de gastroenterólogos y pacientes con EII. Métodos: Se realizó una encuesta online a 8000 pacientes de ACCU-España y 1000 miembros de GETECCU. Se enviaron tres invitaciones entre Octubre-Diciembre 2020. Se realizó un análisis descriptivo, comparando las respuestas de médicos y pacientes. Resultados: 144 gastroenterólogos [63% mujeres, edad media 43 años (DE 9,5)], y1302 pacientes [72% mujeres, edad media 43 años (DE 12)] respondieron a la encuesta. 95% de los médicos recomendaban la vacuna frente a SARS-CoV-2 en pacientes con EII, 87% consideraron que su estrategia de vacunación frente a diferentes vacunas no había cambiado tras la pandemia frente al 12% que consideraban que actualmente remitían más pacientes a vacunación. En cuanto a los pacientes con EII, sólo 43% aceptaban la vacunación frente a SARS-CoV-2, frente a 43% que no estaban seguros. El sexo masculino (p

Goals:We aim to describe the efficacy, safety profile, and variables associated with survival in patients with hepatocellular carcinoma (HCC) treated with sorafenib in South America.Background:Sorafenib has been shown to improve survival in patients with advanced HCC. There are few data on sorafenib use for HCC in South America.Study:We performed a retrospective analysis of HCC cases treated with sorafenib from 8 medical centers in 5 South American countries, between January 2010 and June 2017. The primary endpoint was overall survival (OS), which was defined as time from sorafenib initiation to death or last follow-up. Risk factors for decreased OS were assessed using Cox proportional hazard regression and log-rank tests.Results:Of 1336 evaluated patients, 127 were treated with sorafenib and were included in the study. The median age of individuals was 65 years (interquartile range, 55 to 71) and 70% were male individuals. Median OS in all patients was 8 months (interquartile range, 2 to 17). Variables associated with survival on multivariate analysis were platelets >//

BACKGROUND There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (

Introduction: Ulcerative colitis (UC) is a chronic disease of the digestive tract and up to 20-30% of UC patients may suffer a severe flare-up during the course of the disease. Although there are national and international recommendations about its clinical management, there is not enough information about the treatment of acute severe UC in clinical practice. Methods: An electronic and anonymous survey with 51 multiple-choice questions was performed among all the members of the Spanish Crohn's Disease and Ulcerative Colitis Working Group (GETECCU). Results: Out of the 164 responders (20%), most were gastroenterologists (95%), with 59% from tertiary hospitals treating a median of 5 patients per year (IQR: 3-8) with a severe flare-up of ulcerative colitis. An endoscopic examination was routinely performed in 86% of patients (62% at admission). The most commonly used corticosteroid was methylprednisolone, usually at a dose of 60 mg/day, and its response was assessed after a median of 3 days (IQR: 3-5). Both in thiopurine-naive and thiopurine-refractory patients, infliximab was the drug most frequently prescribed as rescue therapy. Half of responders (55%) had ever prescribed a first dose of infliximab higher than 5 mg/kg, and a higher proportion (73%) had ever prescribed an earlier dose of infliximab in the second or third infusion. Conclusions: Acute severe UC is generally managed according to current treatment guidelines in our setting. The rescue therapy most commonly prescribed is infliximab, and the use of intensified or accelerated regimens with this biological drug is not unusual. (C) 2018 Elsevier Espana, S.L.U. All rights reserved.

Resumen Introduccion La colitis ulcerosa es una enfermedad cronica del tracto digestivo, y hasta el 20-30% de los pacientes sufren un brote grave durante su evolucion. Aunque existen guias nacionales e internacionales sobre el tratamiento de la colitis ulcerosa aguda grave, desconocemos como se manejan en la practica clinica estos pacientes en nuestro medio. Metodos Realizamos una encuesta electronica y anonima entre los miembros del Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU), compuesta por 51 preguntas con respuestas predefinidas. Resultados Participaron 164 miembros (20%), en su mayoria especialistas de aparato digestivo (95%). El 59% trabajaban en hospitales terciarios, atendiendo a una mediana de 5 pacientes al ano (RIC: 3-8) con un brote grave de colitis ulcerosa. El 86% realizan un estudio endoscopico rutinario, habitualmente al ingreso (62%). El corticoide mas empleado es la metilprednisolona, habitualmente a una dosis de 60 mg/dia, y se evalua su respuesta pasados 3 dias (mediana, RIC: 3-5). El tratamiento de rescate usado con mas frecuencia es infliximab, tanto en pacientes naive como refractarios a tiopurinas. El 55% han indicado en alguna ocasion una dosis de infliximab mayor de 5 mg/kg durante la induccion, y el 73% han adelantado alguna de las sucesivas infusiones. Conclusiones El manejo de la colitis ulcerosa aguda grave en nuestro entorno se ajusta en general a las recomendaciones de tratamiento actuales. El tratamiento de rescate mas frecuentemente prescrito es el infliximab, y no es excepcional el empleo de pautas intensificadas o aceleradas de este biologico.

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.

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.

Background Despite the existence of specific recommendations, patients with inflammatory bowel disease (IBD) have shown low immunization rates. The aim of this study was to evaluate the adherence to vaccination recommendations by physicians to their IBD patients. Methods An online anonymous survey was sent to 8000 patients from a national patient association (ACCU-Spain). Three invitations were sent between October-December 2020. Questions were jointly designed by ACCU and GETECCU. Potential reasons for vaccination compliance were evaluated and analysed for different vaccines: age, gender, type of IBD, type of healthcare and treatments. Descriptive analyses and logistic regression were performed to identify factors associated with adherence to vaccination recommendations. Results 1302 patients with IBD responded to the survey (mean age 43 years [SD 12], 72% women). Forty percent of patients had ulcerative colitis, 58% Crohn’s disease and 2% indeterminate colitis. 91% of patients were treated in public facilities, 5% in a private setting and 4% in both. 41% of patients were treated with 5ASA, 35% with azathioprine/methotrexate, 50% with biologics and 8% with corticosteroids. Although [IRL1] [YZ2] physicians recommended vaccination, 45% were not adherent to papilloma virus vaccine, 18% to pneumococcus, 18% to hepatitis B vaccine, 16% to influenza and 12% to tetanus. The main reason for non-compliance to physician recommendation was considering that is not necessary (Table 1). Some factors associated to vaccine compliance are shown in Table 2. Conclusion Non-adherence to vaccination recommendations in IBD patients is frequent. Patients with immunosuppressive therapy show less compliance to the vaccination recommendations. The importance and benefits of vaccination needs to be explained to improve the adherence in IBD patients.

Background Lack of adherence in patients with inflammatory bowel disease (IBD) is a relevant problem in our clinical practice. Non-adherence to anti-TNF increases healthcare costs. The aim of this study was both to measure adherence and also to study the factors and consequences related to non-adherence in patients with IBD under maintenance treatment with infliximab (IFX). Methods A prospective, observational cohort study was designed and patients with IBD under treatment with IFX were consecutively included. Adherence was measured with pharmacy refills and Morisky Medication Adherence Scale-8 (MMAS-8). Patients were systematically asked about adherence and the mean displacement days, the accumulated delay, the mean delay and the medication possession ratio (MPR) were calculated. MPR was calculated by dividing the number of days supplied within the refill interval by the number of days in the actual refill interval over 24 months. Potencial risk factors for non-adherence were evaluated: age, gender, disease duration, site of disease, behaviour of Crohn’s disease (CD), smoking status, educational level, marital status, type of housing, extraintestinal manifestations, previous surgery, concomitant treatments, anxiety and depression. Relapse was defined as a Harvey Bradshaw score > 4 in CD and a partial Mayo > 2 in ulcerative colitis (UC). The Mann-Whitney Wilcoxon U Test was used to distinguish the intergroup differences. Correlations were evaluated with Spearman rank correlation coefficients. Results Ninety patients with mean age 46 years (range: 22–85) were included. 49 (54.4%) were women and 63 (70%) had CD. Anxiety occurred in 38.9% of patients and depression in 78.9%. Three quarters of the patients were in clinical remission at inclusion. After 24 months of follow-up, 82 (91.1%) had delayed some dose of treatment, 35 (38.9%) had delayed on at least 7 days some dose of treatment, and 11 (12.2%) had not received some of the scheduled doses. The MPR was 87% (range 46–100). Lack of adherence was related to loss of response to IFX in CD (p = 0.035), but not in UC (p=0.078). In UC, lack of adherence was related with anxiety (p=0.046). The Spearman’s correlation between older age and non-adherence was 0.53 (p=0.006) in UC and 0.1 (p=0.308) in CD. Conclusion Lack of adherence is related to loss of response to IFX in CD. Non-adherence to IFX is high and strongly associated with age in UC. Older patients with UC are more prone to lack of adherence.

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 Pouchitis and other inflammatory pouch diseases (IPD) are frequent in pouch-carrying patients operated for a previous diagnosis of ulcerative colitis. We evaluated characteristics and differences in therapeutic requirements between pouchitis, Crohn′s-like disease of the pouch (CDP) and cuffitis. Methods This is a retrospective and multicentric Spanish cohort of GETECCU (RESERVO Study), including pouch-carrying patients (operated 1995 to 2016) with previous ulcerative colitis, ileostomy closure and subsequent diagnosis of IPD (pouchitis, CDP or cuffitis), following ECCO diagnostic criteria1. Follow up extended to June 2020. Pouchitis was categorized attending current classifications. Use of medical and surgical therapies was collected and differences between pouchitis and CDP were analyzed using descriptive and comparative statistics. Results A total of 338 patients were included. Demographic and clinical characteristics are presented in Table 1. The most frequent IPD was pouchitis (n=258, 76%), followed by CDP (n=55, 16%) and cuffitis (n=25, 7.4%). Pouchitis was diagnosed at a median time of 27 (range 1–342) months. Prevalence according to pouchitis classification is presented in Figure 1. CDP was diagnosed at a median time of 77 (range 5–324) months, around 75% with a previous pouchitis diagnosis. Location of CDP (not mutually excludent) was pouch CDP (91%), 87% pre-pouch ileitis, and 41% perianal disease. Regarding behavior: 26 (47%) were inflammatory, 12 (22%) stricturing and 17 (31%) penetrating (8 rectovaginal fistulas). Cuffitis was diagnosed at a median time of 18 (range 1–219) months. Medical and surgical therapies used are shown in Figure 2. Immunosuppressants (58.2 vs 22.4%, p 0.001), biologics (74.5 vs 34.8%, p 0.0001), and surgery (41.8 vs 21.3%, p 0.003) were more used in CDP than in pouchitis. Conclusion Pouchitis and CDP are heterogeneous inflammatory pouch complications with a wide and high therapeutic requirement. CDP presents a later diagnosis and has higher therapeutic needs than pouchitis. 1. Fernando Magro, Paolo Gionchetti, Rami Eliakim et al, for the European Crohn’s and Colitis Organisation [ECCO], Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders, J Crohns Colitis 2017; 11(6): 649–670.

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 Patients with colon Inflammatory Bowel Disease (IBD) have a higher risk of colorectal cancer (CRC) than general population. Current guidelines establish endoscopic surveillance recommendations; however, epidemiological studies show poor compliance. The main aim of our study was to analyse adherence to endoscopic surveillance guidelines. Secondary aim was to evaluate the prevalence and time-to advanced lesions or CRC. Methods Retrospective multicentre study of patients with IBD followed-up in the participating centres between 2005 and 2020, who were diagnosed of IBD between 2005 and 2008, with criteria for CRC surveillance. Patients with CRC before IBD diagnosis were excluded. The ECCO 2013–2017 guidelines were used to evaluate adherence. Adenomatous lesions with >25% of villous component, >1cm or with high-grade dysplasia or serrated lesions >1cm or with any degree of dysplasia were considered advanced lesions. Software used for all analysis was R in its 3.6.1 version. Normality was checked with the Shapiro-Wilks test. Mean comparison was carried out using t-Student test while normality assumptions held true, otherwise, Mann-Whitney test. Time-to advanced lesions or CRC event between patients that had adherence to ECCO guidelines versus those who did not was performed through Kaplan-Meier and Log-rank test. P-values below 0.05 were considered significant. Results A total of 1004 (713 Ulcerative Colitis, 252 Crohn’s disease and 39 Indeterminate Colitis; 52% male) patients from 25 centres were recruited with a median age of 36 (26–47) years. 87% of all patients were included in the endoscopic surveillance programme. The main reasons for non-inclusion were the absence of indication by the physician (38%) and the presence of inflammatory activity (37%). Adherence to the first or subsequent surveillance colonoscopies was 45% and 61%, respectively, with a total adherence rate of 32%. Prevalence of advanced lesions or CRC was 4% and 7 cases of CRC were detected. Time-to-detection of these lesions since IBD diagnosis was significantly longer in non-adherent patients (13.4 + 1.3 vs13.04 + 1.7; p Conclusion Adherence to ECCO guidelines for endoscopic surveillance is low in this Southern European population. A higher and earlier detection of advanced lesions or CRC was identified in the adherent group. The results of this study highlight the need to improve compliance with the recommendations to obtain better outcomes.

Background:The novel coronavirus emerged in 2019 in Wuhan has caused a global pandemic of coronavirus disease (COVID-19). Immune-mediated diseases (IMID), as inflammatory arthritis or inflammatory bowel disease (IBD), have some special implications due to their pathogenesis and treatments. Some treatments employed in IMID are now being used in the treatment of severe COVID-19. There still exists controversy about IMID behavior and its complications.1, 2Objectives:To assess COVID-19 severity in IMID patients and its prognosis predictors.Methods:An observational retrospective multicenter study was performed in two Spanish Hospitals (Clinical University Hospital in Santiago de Compostela and Gregorio Marañón Hospital). Patients were selected if they were diagnosed of an IMID (rheumatoid arthritis, psoriatic arthritis, espondyloarthritis, ulcerative colitis and Crohn’s disease) and had COVID-19 infection between February and April 2020.Demographic, clinical, analytical and treatment data were collected. Logistic regression was used to evaluate potential predictors.Stata 15.1 was used to perform statistical analysis.Results:91 patients were recruited. 55 suffered from a rheumatic disease and 36 suffer IBD. Baseline characteristics are shown in Table 1.Univariable analysis reached age, comorbidity, female gender, flu vaccine, arthropathy, basal classical synthetic anti-rheumatic drugs (csDMARD), pneumonia and basal C-reactive protein (CRP) as potential predictors of non-severe (absence of death, respiratory insufficiency, intensive care unit admission or sepsis) COVID-19 disease (p < 0.2). After multivariable analysis, only female gender (OR 4.60 [CI95% 1.00, 21.2] p=0.050), lower age (OR 0.94 [CI95% 0.88, 1.00] p=0.042) and lower basal levels of CRP (OR 0.87 [CI95% 0.77, 0.97] p=0.010) were predictors for non-severe disease (p < 0.005).Mean time of healing (symptoms solved in outpatient and hospital discharge in admitted) from COVID-19 was 13.8 days (SD 16.3). Univariable analysis showed arthropathy, COVID-19 symptomatic and basal glucocorticoids (GC) dose as potential predictors of higher time-to-healing from COVID-19 disease (p < 0.2). After multivariable analysis, only lower GC basal dose predicts higher time-to-healing (OR -1.83 [CI95% -2.81, -0.84] p=0.001).11 patients deceased because of COVID-19. Univariable analysis reached age, basal csDMARD, pneumonia and basal CRP as potential predictors of COVID-19 mortality (p < 0.2). After multivariable analysis, only higher age was a predictor for mortality (OR 1.14 [CI95% 1.04,1.25] p=0.006).Conclusion:IMID patients showed similar predictors of mortality than general population involving COVID-19. Immune-modulating agents did not seem to overshadow the prognosis of COVID-19 infection. Female gender, lower age and lower basal CRP could select a cohort of “good” prognosis patients with mild COVID-19 disease as well higher age points out the worst prognosis. Even that, each case should be individiualized.References:[1]Ceribelli A, et al. Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy. J Autoimmun. 2020;109:102442.[2]Micaela F, et al. COVID-19 in patients with rheumatic diseases in northern Italy: a single-centre observational and case-control study. Lancet Rheumatol 2020;2:e549-56.Table 1.baseline characteristics between non-severe and severe COVID-19 patients.VariablesNon-severe (67)Severe (24)p-valueAge, mean (SD)56.8 (14.6)70.2 (13.7)0.000Female, n (%)38 (63.3)10 (41.7)0.070HLA-B27 +, n (%)9 (17.7)2 (10.0)0.423Disease evolution (years), median (IQR)12.5 (5;24)14 (9;20)0.891Comorbidity, n (%)35 (59.3)21 (87.5)0.013Flu vaccine, n (%)51 (85.0)23 (95.8)0.166Basal GC, n (%)18 (30.0)12 (50.0)0.084csDMARD, n (%)32 (47.8)16 (66.7)0.111b/tsDMARD, n (%)35 (52.2)11 (45.8)0.590COVID-19 symptoms, n (%)55 (93.2)24 (100)0.191Pneumonia, n (%)31 (51.7)21 (87.5)0.002Admission, n (%)30 (50.0)23 (95.8)0.000CRP, median (IQR)3.5 (2;9)10.0 (3;20)0.005Disclosure of Interests:None declared

Background Inflammatory Bowel Disease (IBD) is a multifactorial pathology with an increasing incidence. There are environmental factors, many unknown, that participate in its development. There is no study having assessed a possible relationship with residential radon exposure, which is very high in the study area. The aim of this study was to analyze if residential radon concentration measured at a municipal level is associated with a higher incidence of IBD and its characteristics (clinical or demographic). Methods We performed an ecological study where we included all incident cases of IBD in the area of Santiago de Compostela between January and December 2017 in order to estimate municipal incidence rates. Radon levels at a municipal level were obtained from the Galician Radon Map and correlated with demographic factors and type of IBD. We used the Spearman’s correlation coefficient to test the existence of any association. Results 96 patients were included, 63 (65.6%) with Ulcerative Colitis, 29 (30.25) with Crohn’s Disease and 4 (4.2%) with indeterminate colitis. Median age was 41 (IQR: 33.5 to 56 years), and 50.0% were women. The incidence rate per 100.000 inhabitants-year in the study area was 21.6 cases. The median radon concentration was 104.9Bq/m3 (IQR: 91.0 to 154.6), without statistically significant differences in function of the location of the house (rural vs. urban) nor the type of edification (flat vs house), p >0.05. There were no statistically significant differences on the type of IBD developed (ulcerative colitis, Crohn’s disease or indeterminate colitis) regarding radon levels either (p>0.05). There were no statistically significant differences (p>0.05) between radon and sex of IBD cases. No correlation between radon levels and age of the individuals was observed (Spearman’s rho = -0.13, p-value 0.2), nor radon levels variation by age groups (p>0.05). There was no correlation between radon concentration and cumulative incidence of IBD at municipal level (Spearman’s rho = 0.13, p-value 0.5), as it is shown in figure 1. Conclusion In the area of Santiago de Compostela there is a higher incidence of IBD in comparison with previous studies taking western countries as reference. It is possible that some environmental risk factors, could be responsible of this difference. In this study we have not found any correlation with municipal average radon concentration and incidence of IBD or any of its types.

Background Despite the existence of specific recommendations, patients with Inflammatory Bowel Disease (IBD) have shown low immunization rates. The aim of this study was to evaluate the management of vaccines in clinical practice in IBD from the perspective of physicians and patients. Methods An online anonymous survey was sent to 8000 patients from a national patient association (ACCU-Spain) and 1000 members of the Spanish IBD Working Group (GETECCU). Three invitations were sent between October-December 2020. Forty questions were jointly designed by ACCU and GETECCU in two different surveys for physicians and patients. Descriptive analyses were performed, comparing physician’s and patient’s responses by standard statistical analyses Results 144 physicians and 1302 patients responded to the surveys (overall mean age of 43 years (SD 9.5). 65% of physicians managed more than 200 patients and 80% had >5 years of experience. Most physicians (99%) were concerned about vaccines in IBD patients in their clinical practice, and 63% of them considered vaccines very important. Only 3.5% of physicians recommended live vaccines for their IBD patients with immunosuppressive treatments. One third of physicians did not recommend HPV vaccine. In spite of 69% of physicians recommending influenza vaccine during pregnancy, only 7.2% of pregnant patients indicated that they had received advice on influenza vaccination on their pregnancy (p Conclusion Deficiencies in knowledge regarding vaccination of IBD patients can be frequent. The perspective of physicians and patients is different, with physicians perceiving more recommendations related to vaccines than patients were recommended.

Background Extra-intestinal manifestations (EIM) are frequently reported in inflammatory bowel diseases (IBD). Although the efficacy of TNF inhibitors is well documented, data regarding the effect of vedolizumab (VDZ) and ustekinumab (UST) are limited. Theoretically, the advantage of VDZ, i.e. gut-selectivity, may reduce the efficacy on EIM while the systemic effect of UST may be of benefit. Therefore, we evaluated the differences in new onset and evolution of EIM during both treatments. Methods An international multicentric retrospective study was performed on IBD patients who started VDZ or UST between May 2010 and December 2020. EIM were assessed at baseline and during follow-up. Arthropathy was defined as joint inflammation (arthritis/sacroiliitis) and arthralgia as articular pain without confirmed inflammation. Skin EIM included erythema nodosum (EN), pyoderma gangrenosum (PG) and Sweet syndrome. Ocular EIM included (epi)scleritis and uveitis. Uni- and multivariate analyses were performed. Results In total 856 patients were included: 528 treated with VDZ and 328 with UST. At baseline, arthropathy was more prevalent in UST treated patients (12.2% vs 7.2%; p=0.037; Table 1). No differences in rates of new onset (Fig 1) or evolution of pre-existing arthropathies could be identified between VDZ and UST. In multivariate analyses new onset arthropathy was not associated with smoking, IBD type, sex nor studied biological. In 5 out of 48 (10.4%) VDZ patients and 2 of 46 (4.3%) UST patients with either pre-existing or new arthropathy, treatment was stopped due to articular disease (difference not significant). In contrast, new arthralgia onset within 1 year of follow-up was significantly associated with VDZ treatment (OR 2.1 (1.1–4.0); p=0.022; Fig 1). Arthralgia was the reason to stop treatment in 2 of 87 (2.3%) VDZ patients and never in UST patients. Beside joint EIM, 2 patients developed EN, 1 PG and 1 episcleritis during VDZ treatment. Under UST treatment 1 patient developed EN. No patients developed new Sweet syndrome, scleritis nor uveitis. Conclusion No differences in the rate of new arthropathy onset were observed between VDZ and UST. In contrast, VDZ treatment did increase the risk of new onset arthralgia.

Background The novel coronavirus emerged in 2019 in Wuhan has caused a global pandemic of coronavirus disease (COVID-19). Immune-mediated diseases (IMID), as inflammatory arthritis or inflammatory bowel disease (IBD), have some special implications due to their pathogenesis and treatments. Some treatments employed in IMID are now being used in the treatment of severe COVID-19. There still exists controversy about IMID behavior and its complications. Our aim was to assess COVID-19 severity in IMID patients and its prognosis predictors. Methods An observational retrospective multicenter study was performed in two Spanish Hospitals (University Clinical Hospital in Santiago de Compostela and Gregorio Marañón Hospital). Patients were selected if they were diagnosed of an IMID (rheumatoid arthritis, psoriatic arthritis, espondyloarthritis, ulcerative colitis and Crohn’s disease) and had COVID-19 infection between February and April 2020. Demographic, clinical, analytical and treatment data were collected. Stata 15.1 was used to perform statistical analysis. Results 91 patients were included. 55 suffered from a rheumatic disease and 36 suffered IBD. Univariable analysis reached age, comorbidity, female gender, flu vaccine, arthropathy, basal csDMARD, pneumonia and basal CRP as potential predictors of non-severe (absence of death, respiratory insufficiency, intensive care unit admission or sepsis) COVID-19 disease (p < 0.2). After multivariable analysis, only female gender (OR 4.60 [CI95% 1.00, 21.2] p=0.050), lower age (OR 0.94 [CI95% 0.88, 1.00] p=0.042) and lower basal levels of CRP (OR 0.87 [CI95% 0.77, 0.97] p=0.010) were predictors for non-severe disease (p < 0.005). Mean time of healing (symptoms solved in outpatient and hospital discharge in admitted) from COVID-19 was 13.8 days (SD 16.3). Univariable analysis showed arthropathy, COVID-19 symptomatic and basal GC dose as potential predictors of higher time-to-healing from COVID-19 disease (p < 0.2). After multivariable analysis, only lower GC basal dose predicts higher time-to-healing (OR -1.83 [CI95% -2.81, -0.84] p=0.001).11 patients deceased because of SARS-CoV-2 infection. Univariable analysis reached age, basal csDMARD, pneumonia and basal CRP as potential predictors of COVID-19 mortality (p < 0.2). After multivariable analysis, only higher age was a predictor for mortality (OR 1.14 [CI95% 1.04,1.25] p=0.006). Conclusion IMID patients showed similar predictors of mortality than general population involving COVID-19. Immune-modulating agents did not seem to overshadow the prognosis of COVID-19 infection. Female gender, lower age and lower basal CRP is associated with mild COVID-19 disease as well higher age points out the worst prognosis. Even that, each case should be individualized.

Resumen Introduccion El desarrollo de dependencia a corticoides es frecuente en pacientes con colitis ulcerosa (CU). El objetivo de este estudio fue evaluar la eficacia clinica de ADA, entendida como mantenimiento de remision sin corticoides, en pacientes con CU dependiente de corticoides. Metodos Estudio multicentrico, abierto y retrospectivo. Se incluyeron pacientes con CU dependiente de corticoides segun criterios de la ECCO. Todos los pacientes recibieron ADA para la induccion 160/80 mg y posteriormente 40 mg/2 semanas. En caso de perdida de respuesta se acorto el intervalo de administracion o se duplico la dosis segun criterio medico. Los resultados se expresan como media e IC 95% y se analizaron mediante analisis multivariante. Resultados Se incluyeron 37 pacientes con CU dependiente de corticoides tratados con ADA (67% mujeres), 65% E3, 12 (32%) naive a anti-TNF y 25 (68%) habian recibido previamente infliximab. Un 43% necesitaron intensificacion con ADA. Tras la induccion, el 35% estaba en remision sin corticoides, manteniendola a los 12 meses el 40% de los pacientes. El Mayo parcial basal fue de 6,89; de 3,13 en el mes 6 y de 2,33 en el mes 12. El 48% de los pacientes alcanzaron curacion mucosa. Solo 3 pacientes (8%) necesitaron colectomia en el seguimiento. En el analisis multivariante, una menor tasa de remision se asocio al tratamiento previo con infliximab (HR = 12,8; IC 95% 2,24-73,54; p = 0,004). Conclusiones Adalimumab puede ser eficaz para conseguir la remision clinica sin esteroides y la curacion mucosa en pacientes con CU dependiente de corticoides. El uso previo del infliximab es un factor predictivo de menor eficacia.

Background Genotyping of ctDNA characterizes the molecular profile and monitors tumor molecular dynamics, but the clinical applicability of next generation sequencing (NGS) DNA sequencing has not been assessed in a large prospective cohort of mCRC patients (pts). Methods mCRC pts with RAS wt tumors treated in first line with chemotherapy (CT) + cetuximab in 16 Spanish hospitals were included. Plasma samples were collected baseline (BL) and every 2 cycles until progression. ctDNA was isolated and sequenced with NGS platform Oncomine Colon cfDNA Assay which identifies hotspot mutations (mut) in AKT1, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, GNAS, KRAS, MAP2K1, NRAS, PIK3CA, SMAD4, TP53 and APC. RAS ctDNA mut were also assessed by dPCR (BEAMing) at BL. Detection of any mut in plasma was considered as ctDNA+. Mut in BRAF/RAS/MAP2K1/PIK3CA were considered as anti-EGFR resistance. Results 101 pts were enrolled (65.3% male; median age 64.5y; 77.6% left colon). RAS mut were detected in 11 pts BL by BEAMing. After quality assessment, 84 samples were sequenced by NGS BL and at least one mut was detected in 65 samples (77.3%; median 1, range 0-5) and 10 RAS mut were detected. Plasma samples from 47 pts were also analyzed after 4 cycles of treatment (C4) and mut were detected in 30 pts (63.8%; median 1, range 0-3). Median mutant allele fraction for paired samples was 24.9 at BL and 0.56 at C4 (p = 0.0045). Treatment clinical benefit (CB: PR, CR and SD ≥ 16weeks) was observed in 72 out of 85 pts. BL ctDNA+ or C4 ctDNA change were not associated with CB (p = 0.722). Assessment of RAS BL mut was not associated with CB (p = 0.243 by NGS and p = 0.712 by BEAMing), while the absence of RAS mut at C4 predicted treatment CB (93.2% vs. 6.8% RAS mut p = 0.02). Median PFS for all pts was 10.13 month. ctDNA+ at BL or C4 were not correlated with PFS (HR 0.8; p = 0.73). No differences in PFS were found in ctDNA RAS mut vs RAS wt BL (BEAMing+ HR = 1.2 p = 0.79 and NGS+ HR = 2.6 p = 0.052). Among all anti-EGFR resistant mut, only ctDNA RAS mut were detected at C4 (N = 4). Persistence or emergence of RAS mut at C4 were strongly associated with PFS (12.9m vs. 4.2. HR 8.8 p = 0.0003). Conclusions Early RAS ctDNA dynamics predicts benefit to first line CT+cetuximab in mCRC pts. Legal entity responsible for the study Grupo de Tratamiento de los Tumores Digestivos (TTD), Spain. Funding Merck-Serono. Disclosure J. Vidal Barrull: Honoraria (self), Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Amgen; Honoraria (self): Sysmex-Inostics. E. Elez Fernandez: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck-Serono; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi. F. Losa: Honoraria (self): Amgen; Honoraria (self): Merck-Serono. R. Salazar: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Guardant-Helth; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Ferrer; Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: MSD. J. Tabernero: Honoraria (self), Advisory / Consultancy: Array Biopharma; Honoraria (self), Advisory / Consultancy: Merck-Serono; Honoraria (self), Advisory / Consultancy: Molecular Partners; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Foundation Medicine; Honoraria (self), Advisory / Consultancy: Halio DX SAS. E. Aranda Aguilar: Honoraria (self): Celgene; Honoraria (self): Merck-Serono; Honoraria (self): Roche; Honoraria (self): Sanofi. B. Bellosillo: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Biocartis; Advisory / Consultancy: Novartis; Advisory / Consultancy: Thermofisher. C. Montagut Viladot: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck-Serono; Advisory / Consultancy: Sysmex-Inostics; Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Biocartis; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Guardant-Helth; Advisory / Consultancy: Symphogen. All other authors have declared no conflicts of interest.

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 Approximately one half of the patients with Crohn’s disease (CD) develop intestinal strictures during their lifetime. The effectiveness of currently approved drugs in fibrosis-predominant lesions is very limited. Our aim was to determine the effectiveness of anti-TNF therapy in CD complicated by symptomatic intestinal strictures in a real-world setting. Methods We included adult patients with symptomatic stricturing CD receiving their first-line anti-TNF therapy. Strictures were defined as constant luminal narrowing with pre-stenotic dilatation. We excluded those patients with previous anti-TNF exposure, surgery or endoscopic therapy of the stenosis. The effectiveness of the anti-TNF was defined as a composite outcome combining the persistence of the treatment and without dose or frequency intensification, with no new immunomodulators, surgery or endoscopic therapy during follow-up. A multivariate Cox regression was performed and the final multivariate model was determined using a backward procedure. Results A total of 262 patients from 32 sites were included (141 received infliximab and 121 adalimumab). The median number of stenosis per patient was 1 (range 1–9). The treatment was effective in 81% and 59% of patients after 6 and 12 months, respectively, while this outcome was fulfilled by 21% after a median of 40 months (IQR, 19–85). During follow-up, anti-TNF therapy required a dose or frequency adjustment in 39% of patients, 12% required a new immunomodulator or endoscopic therapy in 4%. The proportion of subjects requiring surgery was 15% and 21% after 1 and 2 years, respectively, with an overall rate of surgery of 32%. Infliximab was associated with a higher rate of surgery as compared with adalimumab (OR 1.78; 95% CI, 1,025-3,09). A shorter time since the diagnosis of CD or the stricture and the initiation of anti-TNF therapy was associated with a greater effectiveness at 6 and 12 months (HR 0.99 95% CI 0.99–1, p = 0.045; HR 0.99 95% CI 0.99–0.99, p = 0.015; HR 0.98 95% CI 0.96–0.99, p = 0.024; HR 0.99 95% CI 0.98–1.0, p = 0.046; respectively). In the survival analysis, younger age, lower albumin levels at baseline, strictures being located in the descending colon, concomitant use of mesalamine and the presence of ulcers or lymphadenopathy at the stricture were associated with lower effectiveness. The anti-TNF agent was discontinued in 131 patients (50%), and 88 subjects (34%) required a switch to a new biologic. Conclusion Anti-TNF agents are effective in approximately 20% of patients with CD complicated with symptomatic strictures. Early introduction of anti-TNF therapy improves the effectiveness in the short term in these patients. Some clinical and radiological predictors can identify patients with a lower probability of response.

Background Ulcerative colitis (UC) is a chronic, progressive and disabling disease with a complex pathology of unknown aetiology influenced by genetic, environmental and microbiota factors that lead to an immunological and inflammatory response in the colon. Janus Activated Kinase (JAK) family plays a key role in modulating the adaptive and innate inflammatory response. The JAK/STAT pathway involvement in UC has been demonstrated in both animal models and human studies. Thus, overexpressed JAK-3 has been detected in the intestine of patients with UC, suggesting a key role in their pathophysiology and the inhibition of TYK-2 in animal models resulted in an improvement of the disease, which would explain its implication in the inflammatory process. We hypothesise here that there could be an activation of JAK-3 and TYK-2 signalling pathways in UC patients. Thus, we aimed to detect the activation of both signalling pathways by means of western-blot studies in UC patient samples Methods A prospective, observational single-centre study was designed. Inclusion criteria were adult patients with endoscopic active UC (more than Mayo-0) confirmed in a programmed colonoscopy. All patients signed informed consent. Samples were obtained from overstock of routine biopsies in the more severe segment affected of the large bowel. Tissues were homogenised and processed in order to obtain cell lysates by employing RIPA buffer and ultrasounds. The degree of activation of the JAK-3 and TYK-2 pathways was measured by detecting the phosphorylation of both targets as well as of STAT1, STAT3, STAT4, STAT5 and STAT6 through western blot by employing specific antibodies for total and phosphorylated proteins. Results 19 UC patients were consecutively included. Mean age was 46 years old. 53% were female, 47% were extensive colitis (E3) and 53% left-side colitis (E2). Regarding endoscopic activity, 26% had Mayo-1, 53% Mayo-2, and 21% Mayo-3. Immunoreactive bands for both phosphorylated JAK-3 and TYK-2 were detected in the biopsies from UC patients, evidencing that colonic inflammation leads to an activation of both targets. The study of STATs phosphorylation showed immunoreactive bands for phosphorylated forms of STAT1, STAT3, STAT4, STAT5 and STAT6 confirming the activation of both signalling-pathways in these patients (Figure 1). Conclusion The developed translational workflows involving basic/clinical research confirm the activation of both JAK-3 and TYK-2-dependent signalling pathways in UC patients, validating both kinases as targets for treating UC. The developed methodology allows studying the target engagement for future JAK-3/ TYK-2 inhibitors employed in clinical trials.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death globally. Sorafenib, a multi-tyrosine kinase inhibitor, remains the standard of care for patients with inoperable or advanced-stage HCC. In resource-limited settings without access to surgical or locoregional therapy, sorafenib may be the only option for treating HCC. However, due to a modest survival benefit, as well as the limiting cost of sorafenib in certain regions, appropriate selection of patients for treatment is essential. Evaluation of Barcelona Clinic Liver Cancer (BCLC) criteria in resource-limited settings is frequently unachievable due to a variety of reasons. Using a cohort from the South American liver research network (1336 HCC cases), we created a cost-effective prognostic scoring system to help identify patients likely to have a survival benefit on sorafenib treatment, using simple laboratory variable Fil: Leathers, James S.. Vanderbilt University; Estados Unidos Fil: Balderramo, Domingo. Universidad de Córdoba; España Fil: Prieto, Jhon. Centro de Enfermedades Hepáticas y Digestivas; Colombia Fil: Diehl, Fernando. Universidad de Córdoba; España Fil: Gonzalez-Ballerga, Esteban. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Ferreiro, Melina R.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Carrera, Enrique. Hospital Eugenio Espejo; Ecuador Fil: Barreyro, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina Fil: Diaz Ferrer, Javier. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Singh, Dupinder. University of Minnesota; Estados Unidos Fil: Mattos, Angelo Z.. Universidade Federal de Ciencias Da Saúde de Porto Alegre; Brasil Fil: Carrilho, Flair. Universidade de Sao Paulo; Brasil Fil: Debes, Jose D.. University of Minnesota; Estados Unidos

BACKGROUND Data on the influence of rural/urban and coastal/inland environment on inflammatory bowel disease (IBD) are either conflicting or lacking. Our aim was to analyze whether the environment has any influence on the prevalence, phenotype, and course of IBD. MATERIALS AND METHODS We carried out a multicenter retrospective study in 1194 IBD patients from Galicia, Spain. Urban areas were defined as those with over 25,000 inhabitants. Sex, age, family history, smoking, Montreal classification, extraintestinal manifestations, steroid dependence/refractoriness, and treatment were assessed. We used the Student's t-test/Mann-Whitney U tests to compare continuous variables and χ to compare categorical variables. Logistic regression was also used. RESULTS Living in urban municipalities was a risk factor for Crohn's disease [relative risk (RR) 1.47; 95% confidence interval (CI) 1.25-1.73; P

Background There is no evidence about the time that it is reasonable to wait until starting Vedolizumab (VDZ) or Ustekinumab (UST) in case of loss of response to anti-TNF therapy. The aim of our study was to evaluate whether the time between the change from any anti-TNF drug to VDZ or UST had an influence on the risk of treatment failure and the rate of adverse events or severe infections. Methods A retrospective, observational single-centre study was designed. Inclusion criteria were all adult patients with moderate-to-severe IBD who started treatment with VDZ or UST due to loss of response to anti-TNF (Infliximab or Adalimumab). Exclusion criteria were patients who had received treatment for different indications such as prevention of recurrence or extra-intestinal manifestations. Patients that changed directly from VDZ to UST or from UST to VDZ were also excluded. We defined two groups of periods based on the interval of time between the last dose of anti-TNF and the first dose of VDZ or UST: Group A: early (≤30 days), Group B: late (31–60 days). Patients that had a waiting time of over 60 days were also excluded. Treatment failure after the initiation of VDZ or UST was defined as the need for dose intensification, surgical resection, therapy removal for ineffectiveness or adverse reaction. The existence of infections was also evaluated. Results are shown as percentages, median, range and Hazard Ratio (CI 95%). Fisher test and Cox Regression analysis were also performed. Results 46 patients (45.6% CD) were consecutively included (mean age 47.6 years). 17 had initially been treated with Infliximab and 29 with Adalimumab. Thirty patients were changed to VDZ and 16 to UST. Twenty-three patients were included in Group A and 23 in Group B. Treatment failure was observed in 20 patients: 9/23 in group A and 11/23 in group B with a mean follow-up of 323 days (range 152–432). The duration of the interval of time between stopping anti-TNF and starting VDZ or UST was not associated with increased risk of treatment failure (p = 0.25) with a median of time until loss of response of 252 days (range 98–432 days) in Group A and 168 days (range 131–418 days) in group B (Figure 1). No differences were found between patients with CD or UC (p = 0.23) and no differences were found in starting with VDZ or UST. There was 1 adverse event that forced a stopping of treatment in group A. No infections that required hospitalisation were observed. Conclusion The interval of time between anti-TNF and VDZ or UST had no influence on the rates of treatment failure, adverse events or infections in our cohort.

Background Desensitization to antineoplastic agents is becoming a standard of care. Efforts to establish and improve these techniques are being made at many institutions. Our aims are to evaluate a new rapid desensitization protocol designed to be shorter (approximately 4 h) and safer (reducing hazardous drugs exposure risks) and to assess the oxaliplatin-specific immunoglobulin E (IgE) as a novel diagnostic tool. Methods Prospective, observational, longitudinal study with patients who, for a 1-year period, suffered reactions to antineoplastic agents and were referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were included or excluded as desensitization candidates after anamnesis, skin testing, risk assessment, and graded challenge. Specific IgE was determined in oxaliplatin-reactive patients. Candidate patients were desensitized using the new RCUH rapid desensitization protocol. Results Of 189 intravenous rapid desensitizations, 188 were successfully accomplished in the 23 patients who met inclusion criteria for desensitization (of 58 referred patients). No breakthrough reactions occurred in 94% of desensitizations, and most breakthrough reactions were mild. In 10 oxaliplatin-reactive patients, 38 desensitizations were successfully accomplished. Sensitivity for oxaliplatin-specific IgE was 38% (0.35UI/l cutoff point) and 54% (0.10UI/l cutoff point); specificity was 100% for both cutoff points. Conclusions In the hands of a Desensitization Program, managed by drug desensitization experts, this new protocol has proven an effective therapeutic tool for hypersensitivity to several antineoplastic agents (oxaliplatin, carboplatin, paclitaxel, docetaxel, cyclophosphamide, and rituximab); moreover, it improves safety handling of hazardous drugs. We report the first large series of oxaliplatin desensitizations. Oxaliplatin-specific IgE determination could be helpful.