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Stricture is one of the main complications of Crohn's disease (CD). Among the main conservative therapeutic alternatives, endoscopic balloon dilation (EBD) of the strictures stands out, which can improve the symptoms and delay or even avoid the need for more surgeries. The main aim of this study was to evaluate the efficacy of the EBD in CD patients with post-surgical anastomotic strictures from a previous surgery.An observational study of a cohort of 32 patients with CD who underwent EBD due to uncomplicated strictures at a tertiary hospital, since 2009. Demographic, clinical and disease variables, medical treatments and previous surgeries and types, analytical variables at the time of dilation, number of dilations, complications and need for subsequent surgery were collected by searching data in clinical records.Thirty-two patients were included, performing a total of 63 endoscopic dilations. A technical success of 63.5%, a therapeutic success by dilation of 58.75% and a therapeutic success per patient of 62.5% were achieved. Regarding complications, the percentage of post-dilation adverse events was 3.2% and post-dilation incidents were 4.8%. Thirty EBD did not need any medical treatment modification, 9 EBD remained untreated and 12 EBD required further surgery. The length of the strictures, but not the ongoing treatment, was the only statistically significant factor of therapeutic success by dilation and per patient.EBD seems a safe technique in short post-surgical strictures, can avoid the need for new surgery and prevents unnecessary immunosuppression in patients with CD anastomotic strictures.

Resumen La pandemia COVID-19 ha supuesto un cambio cualitativo en el modo de atender a los pacientes en consultas ambulatorias. La necesidad de toma de medidas de aislamiento social como prevencion para el contagio por el SARS-CoV-2 ha obligado al uso de consultas telematicas y telefonicas en la mayoria de unidades medicas y quirurgicas. La especialidad de Aparato Digestivo, por las caracteristicas de sus pacientes y el apoyo frecuente en tecnicas complementarias para el diagnostico, es especialmente adecuada para realizar consultas no presenciales. En este documento se plantean una serie de recomendaciones que pueden servir como guia para el establecimiento o mejora de consultas no presenciales de Medicina Digestiva.

Background Female gender could be a cause of diagnostic delay in inflammatory bowel disease (IBD). The aim of this study was to investigate the diagnostic delay in women vs men and potential causes. Methods This multicenter cohort study included 190 patients with recent diagnosis of IBD (disease duration Results The median time from symptom onset to IBD diagnosis was longer in women than in men: 12.6 (interquartile range, 3.7-31) vs 4.5 (2.2-9.8) months for Crohn’s disease (CD; P = .008) and 6.1 (3-11.2) vs 2.7 (1.5-5.6) months for ulcerative colitis (UC; P = .008). Sex was an independent variable related to the time to IBD diagnosis in Cox regression analysis. The clinical presentation of IBD was similar in both sexes. Women had a higher percentage of misdiagnosis than men (CD, odds ratio [OR], 3.9; 95% confidence [CI], 1.5-9.9; UC, OR 3.0; 95% CI, 1.2-7.4). Gender inequities in misdiagnosis were found at all levels of the health system (emergency department, OR 2.4; 95% CI, 1.1-5.1; primary care, OR 2.5; 95% CI, 1.3-4.7; gastroenterology secondary care, OR 3.2; 95% CI, 1.2-8.4; and hospital admission, OR 4.3; 95% CI, 1.1-16.9). Conclusions There is a longer diagnostic delay in women than in men for both CD and UC due to a drawn-out evaluation of women, with a higher number of misdiagnoses at all levels of the health care system.

Aims i] To evaluate the evolution of pregnancies and offspring after inflammatory bowel disease [IBD] surgery during pregnancy; and ii] to describe the indications, the surgical techniques, and the frequency of caesarean section concomitant with surgery. Methods Patients operated on due to IBD during pregnancy after 1998 were included. Participating clinicians were asked to review their databases to identify cases. Data on patients’ demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, and foetal and maternal outcomes, were recorded. Results In all, 44 IBD patients were included, of whom 75% had Crohn’s disease; 18% of the surgeries were performed in the first trimester, 55% in the second, and 27% in the third trimester. One patient had complications during surgery, and 27% had postsurgical complications. No patient died. Of deliveries, 70% were carried out by caesarean section. There were 40 newborns alive. There were four miscarriages/stillbirths [one in the first, two in the second, and one in the third trimester]; two occurred during surgery, and another two occurred 2 weeks after surgery; 14% of the surgeries during the second trimester and 64% of those in the third trimester ended up with a simultaneous caesarean section or vaginal delivery. Of the 40 newborns, 61% were premature and 47% had low birth weight; 42% of newborns needed hospitalisation [25% in the intensive care unit]. Conclusions IBD surgery during pregnancy remains an extremely serious situation. Therefore, surgical management should be performed in a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians, and neonatal specialists.

Background: A treat-to-target strategy, in which strictly defined treatment targets facilitate decision making in clinical practice, is advocated as an optimised management approach for some chronic disorders. The aim of the STARDUST trial was to assess whether a treat-to-target strategy with early endoscopy, regular biomarker and clinical symptom monitoring, and dose intensification for persistent inflammatory activity, was more successful in achieving endoscopic improvement at week 48 than a clinically driven maintenance strategy in patients with moderate-to-severe active Crohn's disease receiving ustekinumab. Methods: This open-label, multicentre, randomised phase 3b trial included adults with active, moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220–450 and Simple Endoscopic Score in Crohn's Disease [SES-CD] ≥3) for whom conventional therapy or one biologic therapy, or both, had failed. Patients received intravenous ustekinumab approximating 6 mg/kg at baseline and subcutaneous ustekinumab 90 mg at week 8. At week 16, patients with a CDAI improvement of 70 or more points from baseline were randomly assigned (1:1) to receive standard-of-care or treat-to-target maintenance treatment through week 48. Randomisation was balanced by using randomly permuted blocks and was stratified by biologic history status and baseline SES-CD score. All patients who signed informed consent, who were not screening failures, and who received at least one dose of study treatment were included in week 16 analyses. All patients included in week 16 analyses and randomly assigned to one of the maintenance treatment regimens were included in the week 48 efficacy and safety analyses (ie, on an intention-to-treat basis). Patients assigned to the treat-to-target arm received ustekinumab every 12 weeks or every 8 weeks based on SES-CD improvement from baseline and could escalate to every 4 weeks through week 48 if prespecified targets were missed. Patients assigned to the standard-of-care arm received ustekinumab every 12 weeks or every 8 weeks; those receiving treatment every 12 weeks could escalate per European labelling. The primary efficacy endpoint was endoscopic response at week 48 (SES-CD score ≥50% decrease from baseline), analysed by non-responder imputation. This trial is registered at ClinicalTrials.gov, NCT03107793, and is active but not recruiting. Findings: 498 patients received standard induction treatment, of whom 440 were randomly assigned to the treat-to-target group (n=219) or the standard-of-care group (n=221). At week 48, there was no significant difference in endoscopic response (83 [38%] of 219 patients vs 66 [30%] of 221 patients; p=0·087), endoscopic remission (25 [11%] vs 32 [15%]; p=0·334), mucosal healing (31 [14%] vs 37 [17%]; p=0·449), and clinical remission (135 [62%] vs 154 [70%]; p=0·072) between the two groups; clinical response was significantly lower in the treat-to-target group than in the standard-of-care group (149 [68%] vs 172 [78%]; p=0·020). Other endoscopic, clinical, and biomarker outcomes were generally not significantly different between groups. The most commonly reported treatment-emergent adverse events were nasopharyngitis (29 [13%] of 219 patients in the treat-to-target group vs 29 [13%] of 221 patients in the standard-of-care group), abdominal pain (23 [11%] vs 19 [9%]), arthralgia (24 [11%] vs 19 [9%]), and headache (24 [11%] vs 21 [10%]). Interpretation: Timely escalation of ustekinumab therapy for patients with Crohn's disease, based on early endoscopic response, clinical symptoms, and biomarkers, did not result in significantly better endoscopic outcomes at week 48 than symptom-driven decisions alone. Future studies need to confirm if some subgroups of patient might benefit from a treat-to-target strategy with ustekinumab. Funding: Janssen-Cilag.

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.

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.

Resumen Las tiopurinas (azatioprina y mercaptopurina) se usan frecuentemente en pacientes con enfermedad inflamatoria intestinal. En este documento, revisaremos sus principales indicaciones, asi como aspectos practicos de seguridad, eficacia y modo de empleo. Sus usos principales son el mantenimiento de la remision en la enfermedad corticodependiente o tras el control de un brote grave de colitis ulcerosa con ciclosporina, la prevencion de la recurrencia posquirurgica en enfermedad de Crohn y el empleo en terapia combinada junto con biologicos. El 30-40% de pacientes no respondera al tratamiento y un 10-20% no tolerara el tratamiento por efectos adversos. Antes de iniciarlas, se recomienda evaluar el estado de inmunizacion frente a ciertas infecciones; la determinacion previa de la actividad de la tiopurina·metiltransferasa (TPMT) no es imprescindible, pero permite mayor seguridad inicial. La dosis adecuada es de 2,5 mg/kg/dia para azatioprina y de 1,5 mg/kg/dia para mercaptopurina. Algunos efectos adversos son idiosincrasicos (intolerancia digestiva, pancreatitis, fiebre, artromialgias, exantema y algunos casos de hepatotoxicidad). Otros son dosis-dependientes (mielotoxicidad y otros tipos de hepatotoxicidad) y su vigilancia debe mantenerse mientras dure el tratamiento. Si son ineficaces o aparecen efectos adversos, puede recurrirse al cambio de tiopurina, la reduccion de dosis, combinar dosis bajas de azatioprina con alopurinol y determinar metabolitos antes de descartar su uso. Los tumores de piel distintos al melanoma, los linfomas y los tumores del tracto urinario se han relacionado con su administracion. Las tiopurinas son farmacos seguros en la concepcion, gestacion y lactancia.

Background COVID-19 pandemic increased medical services demand aside from interrupting daily clinical practice for other diseases such as Inflammatory Bowel Disease (IBD). Here we present the results of a survey to gain the perception of IBD specialists in their patient-management using telemedicine in their daily practice. Methods This was an observational survey study among physicians focused on IBD (gastroenterologist, surgeons, and pediatricians) members of the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis (GETECCU), the Spanish Association of Gastroenterology (AEG), and the Spanish Association of Coloproctology (AECP), regarding changes of management of IBD patients. Results We received a total of 269 responses to the survey (from May to June 2020). Before the pandemic, nearly all the respondents reported performing very frequently their visits face-to-face (n=251, 93.3%) while, during the pandemic, the telephone visits were the most frequent visits performed (n=138, 51,3%). Regarding communication difficulties, 157 (58.4%) respondents reported the impossibility of performing a proper examination as the most relevant issue. Also, 114 (42.4%) respondents considered remote visits more time-consuming than face-to-face visits. Most gastroenterologists (n=188, 83.2%) considered patients with active perianal disease in special need of face-to-face consultation and more than half of the surgeons (n=35, 50.7%) reported having performed an immediate postoperative follow-up remotely. Conclusion Most IBD units have implemented remote visits during the pandemic, but most professionals found them more time-consuming and unsuitable for some disease profiles. Therefore, there is a need for the development of better telemedicine systems that can meet professionals’ and patients′ requirements.

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 Ustekinumab (UST) intensification during Crohn’s Disease (CD) treatment is becoming common in clinical practice. Little is known about early intensification maintenance regimens and their drug levels utility in discriminating CD-response and the need for further intensification. We aim to analyze UST levels’ evolution in an intensified maintenance regimen, their capacity to discriminate response according to inflammatory parameters and indicate the need for further intensification. Methods This is a retrospective study with 43 moderate/severe active CD patients (Harvey-Bradshaw Index [HBI] ≥4 and Fecal Calprotectin [FC] >250 µg/g) who received UST induction treatment (induction dose of 6mg/kg IV, plus dose of 90mg SC at week 8). Patients received maintenance treatment (90mg SC/8 weeks) and were followed for 52 weeks. They were classified according to the response obtained at the first year in responders (R), HBI 250µg/g; and intensification group (IG), partially responders that needed UST intensification to every 4 weeks. HBI, FC, C-Reactive Protein (CRP), and UST levels data were collected at baseline (w0), week 8 (w8), week 16 (w16), and 52 weeks (w52) of maintenance. IG was followed 12–26 weeks after intensification (aI). Results Half of the patients (48.8%) were male. Most of them (97.7%) have received previous anti-TNF-α treatment (53.49% ≥2 anti-TNF-α). Patients’ median age at the moment of starting UST was 51 (37.5, 58.5) years. Median disease duration was 11 (7.5, 23) years. Location of disease was ileal in 30% of patients and ileocolic in 53%. One-third of patients suffered perianal disease, and 41 % were smokers. The only demographic factor associated with non-response was ileocolic location. Table 1 shows the evolution of inflammatory parameters and UST levels according to the response. A Pearson correlation (r=0.62) between higher FC drop (baseline-w16) and higher drug levels at w16 was observed. The evolution of biological markers discriminates NR during induction; however, neither biological markers nor UST level can distinguish between R and those who will need intensification. R shows higher UST levels at w52 compared to IG. IG showed a significant increase of UST levels (mean of 5.39 points) and a substantial drop of FC and HBI (mean of 115.62 and 2.27 points, respectively) after intensification. Those patients reported clinical improvement; however, they could not reach a FC Conclusion FC drop-slope is associated with higher levels of UST at the end of induction. UST levels at w52 are useful for discriminating patients who will benefit from UST intensification every 4 weeks.

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

Background: Little is known about the association between the pharmacokinetic features of adalimumab (ADL) and disease outcome in patients with inflammatory bowel disease (IBD). Aims: To assess the association between random serum ADL levels and clinical or biochemical remission with clinical decision making in daily practice according to these levels; and to determine the cutoff value for successful dose reduction in patients with IBD treated with ADL. Methods: We conducted a prospective observational study of patients with IBD who received long-term maintenance therapy with ADL. Results: Data were available for 157 serum samples from 87 patients. Serum ADL levels were associated with clinical remission: median 9.2 versus 6.0 mu g/mL for patients with Crohn's disease with active disease (P = 0.009) and 14.4 versus 5.2 mg/mL in patients with ulcerative colitis with active disease (P = 0.002). Serum ADL levels were 9.2 mg/mL for patients with a normal C-reactive protein value (

Background Despite the continuous adaptation of eHealth systems for patients with inflammatory bowel disease (IBD), a significant disconnection persists between users and developers. Since non-adherence remains high, it is necessary to better understand the patients’ perspectives on telemonitoring for IBD. The aim of this study was to adapt the TECCU app to the preferences and needs of IBD patients. Methods A qualitative study was carried out using successive focus groups of IBD patients. Meetings were audio-recorded and a thematic analysis approach was employed until data saturation was achieved. The first group included patients who had used the TECCU app in a pilot clinical trial, and subsequent meetings included patients with Crohn’s disease and ulcerative colitis recruited from the Spanish Confederation of patient associations. The information collected at each meeting guided consecutive changes to the platform. Results Data saturation was reached after 3 focus groups, involving a total of 18 patients. Three main themes emerged: (1) platform usability; (2) the communication process; and (3) contents of the platform. All participants indicated that TECCU is easy to use, permitting continuous and personalised feedback. Nevertheless, the platform was adapted according to the patients′ perspectives to foster a flexible follow-up and shared decision-making, using open and safe communication networks. Many participants appreciated the educational elements and the app was connected to reliable and continuously updated webpages. Conclusion IBD patients valued the usability and personalised monitoring offered by the TECCU App. Improvements in the messaging system and continuous updates of the educational contents were performed to address patients′ needs and favour their engagement.

This review article summarizes the evidence about telemedicine applications (e.g., telemonitoring, teleconsulting, and tele-education) in the management of patients with inflammatory bowel disease (IBD), and we aim to give an overview of the acceptance and impact of these interventions on health outcomes. Based on the literature search on "inflammatory bowel disease," "Crohn's disease" and "ulcerative colitis" in combination with "e-health," "telemedicine," and "telemanagement," we selected 58 titles and abstracts published up to June 2014 and searched in PubMed, EMBASE, MEDLINE, Cochrane Database, Web of Science and Conference Proceedings. Titles and abstracts were screened for a set of inclusion criteria: e-health intervention, IBD as the main disease, and a primary study performed. Finally, 16 were included for full reading, data extraction, and critical appraisal of the evaluation. Most studies use telemonitoring (home telemanagement system or web portal) and telecare (real-time telephone and image) as telemedicine applications and assessed the feasibility and acceptance of these systems, adherence to treatment, quality of life, and patient knowledge, particularly in patients with ulcerative colitis. Furthermore, some of these studies evaluated the patients' empowerment, health care costs, and safety of telemonitoring in IBD. In conclusion, the health outcomes of telemedicine applications in IBD suggest that these could be implemented in clinical practice because they are safe and feasible applications that are well accepted by the patient and improve adherence, quality of life, and disease knowledge. Further studies with large sample sizes and complex diseases are needed to confirm these results.

BACKGROUND: Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. METHODS: We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. RESULTS: During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age =50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). CONCLUSIONS: The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Thiopurines (azathioprine and mercaptopurine) are widely used in patients with inflammatory bowel disease. In this paper, we review the main indications for their use, as well as practical aspects on efficacy, safety and method of administration. They are mainly used to maintain remission in steroid-dependent disease or with ciclosporin to control a severe ulcerative colitis flare-up, as well as to prevent postoperative Crohn's disease recurrence, and also in combination therapy with biologics. About 30-40% of patients will not respond to treatment and 10-20% will not tolerate it due to adverse effects. Before they are prescribed, immunisation status against certain infections should be checked. Determination of thiopurine methyltransferase activity (TPMT) is not mandatory but it increases initial safety. The appropriate dose is 2.5mg/kg/day for azathioprine and 1.5mg/kg/day for mercaptopurine. Some adverse effects are idiosyncratic (digestive intolerance, pancreatitis, fever, arthromyalgia, rash and some forms of hepatotoxicity). Others are dose-dependent (myelotoxicity and other types of hepatotoxicity), and their surveillance should never be interrupted during treatment. If therapy fails or adverse effects develop, management can include switching from one thiopurine to the other, reducing the dose, combining low doses of azathioprine with allopurinol and assessing metabolites, before their use is ruled out. Non-melanoma skin cancer, lymphomas and urinary tract tumours have been linked to thiopurine therapy. Thiopurine use is safe during conception, pregnancy and breastfeeding.

Background Therapeutic drug monitoring (TDM) is used in inflammatory bowel disease to guide dosing of biologics to individualise drug exposure and optimise outcomes. In case of undetectable levels of Adalimumab (levels Methods Since October 13 to August 19, 758 TDM were performed in 260 patients treated with ADA. We selected the patients who had at least a level Results We identified 46 patients with undetectable levels; 12 were excluded. Thirty-four patients were included, 29 (85.3%) with Crohn’s disease and 5 (14.7%) with ulcerative colitis. Ten (29.4%) patients had combined treatment and 17 (50%) had previously received another anti-TNF. In 24 (70.6%) TDM was performed proactively. After detection of levels 5 μg/ml), 12 (60%) in the intensified-patient group and 2 (14.3%) in the group in whom the treatment was not modified. ADA was withdrawn in 13 patients (32.8%) after a mean time of 358 days (SD 258). The ADA maintenance rate (HR=3.88; 95% CI 1.2–12.4; p = 0.02) and the recovery ratio of ADA levels (HR = 6.75; 95% CI 1.1–39, 8; p = 0.03) was higher in the intensified group. Hypoalbuminemia was associated with an earlier withdrawal of ADA (p = 0.03) Conclusion The intensification of ADA in patients with IBD and undetectable plasma concentrations allows recovery of levels and maintenance of the drug in a high percentage of patients. The decision to withdraw treatment in patients with undetectable levels should be individualised.

Background & aims: Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. Methods: Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (K index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. Results: 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p < 0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (kappa = 0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. Conclusions: Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type. (C) 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

OBJECTIVES: To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. METHODS: Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. RESULTS: Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P = 0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P = 0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P < 0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. CONCLUSIONS: Treatment with CyA showed a lower rate of SAE and a similar effi cacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefi t of sequential CyA-IFX for CyA non-responders is acceptable.

Resumen Introduccion Los fenomenos tromboembolicos venosos y arteriales son una complicacion extraintestinal infrecuente de la enfermedad inflamatoria intestinal (EII) potencialmente prevenible. Caso clinico Varon de 62 anos, con diagnostico de enfermedad de Crohn (EC) (A3, L1 + L4, B3) que durante su ingreso para drenaje percutaneo de absceso retroperitoneal presenta episodio de tromboembolia arterial periferica de miembro superior derecho, que requirio embolectomia urgente. Tras anticoagulacion con heparina de bajo peso molecular (HBPM), se realiza estudio etiologico con hallazgo en la resonancia magnetica vascular de un trombo arterial de gran tamano en la aorta descendente, por lo que se realizo cirugia aortica y se pauto anticoagulacion indefinida con acenocumarol. Conclusion La trombosis arterial periferica es una complicacion poco comun de la EII que debe ser considerada en pacientes con enfermedad activa y prevenida adecuadamente con HBPM. El tratamiento habitual es la cirugia combinada con anticoagulacion y optimizacion de la terapia farmacologica.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic and relapsing disorder characterized by inflammation of the gastrointestinal tract. The natural progression includes periods of flares and remission, requiring continuous and personalized follow-up to achieve long remission and minimize short and long term damage. In fact, IBD patients show significantly higher rates of utilization of healthcare resources than patients with other conditions [1]. It is important to emphasize that 30-45% of adults are nonadherents [2], making these patients five times more likely to suffer relapses and consequently increasing health care costs [3]. The high percentage of nonadherence may be due to the difficulty in accessing specialized IBD care and behavioral factors. Furthermore, IBD is associated with high levels of school and work disability [4], interference with social activities and impairment of quality of life [5]. For these reasons, IBD generates a signi...

A substantial percentage of patients fail to follow health professionals' recommendations, which affects the management of chronic diseases, reducing the effectiveness of therapeutic interventions and increasing the costs of the disease. Lack of adherence is a multidimensional phenomenon and is influenced by numerous factors that should be identified. A multiplicity of measures is available to improve adherence, such as simplifying treatment administration, but none of these measures is effective when used alone. One way of tackling lack of adherence is by identifying patients' barriers to medication and involving them in decision making. Ulcerative colitis (UC) poses a risk for lack of treatment adherence. In this disease, poor adherence correlates with poor disease control (drug effectiveness) and with higher costs. As in other chronic diseases, the causes associated with poor adherence are multiple, including psychosocial factors, the physician-patient relationship and patients' prejudices toward medication. A single dose of aminosalycylates (5-ASA) should be recommended, as this dose is as safe and effective as other regimens. However, by itself, this recommendation does not seem to improve adherence. Identifying the scale of the problem and developing strategies to involve the patient in decision making is crucial to improve treatment adherence.

Background Few data are available on the efficacy of methotrexate (MTX) in ulcerative colitis (UC). Aim To evaluate the efficacy and safety of MTX in UC patients. Patients and methods UC patients who had been treated with MTX were identified from the databases of 8 Spanish IBD referral hospitals. Patients were included in the study if they received MTX for steroid dependency or steroid refractoriness. Therapeutic success was defined as the absence of UC-related symptoms, complete steroid withdrawal and no requirement of rescue therapies within the first 6months after starting MTX. Results Forty patients were included, 70% treated for steroid dependency and 27% for steroid refractoriness. Thiopurines had been previously attempted in 87.5% of patients. The median dose of MTX used for induction was 25mg (IIQ 17.5–25) weekly given parenterally in 82.5% of cases. Eighty-five percent of patients were on steroids when MTX was started. Forty-five percent of patients met criteria for therapeutic success. Initial treatment failures were mainly due to inefficacy (50%) or intolerance (36%). After a median follow-up of 28months (IQR 22–47), 38% of patients with initial therapeutic success required new steroid courses, 22% started biological therapy, and only 1 patient required colectomy. The cumulative probability of maintaining steroid-free clinical remission was 60%, 48%, and 35% at 6, 12, and 24months after starting MTX, respectively. Eleven patients (27.5%) experienced adverse events, leading to MTX discontinuation in only 8 of them. Conclusions MTX appears to be effective to maintain clinical remission in UC, at least in the short-term, with an acceptable safety profile.

Background Epidemiological studies have shown a greater prevalence of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) among first-degree relatives of patients diagnosed of these diseases. However, it is not known whether relatives of patients with IBD have a greater prevalence of IBS than the general population. Aims To analyse the prevalence of IBS among first-degree relatives by consanguinity (parents, siblings and offspring) and affinity (spouses) of patients with IBD. Materials and methods A prevalence study was conducted identifying 490 relatives of 91 patients with IBD. Of these, 404 met inclusion criteria; and 360 (response rate: 89.1%) answered the questionnaires. Subjects were invited to participate in the study through index cases (patients with IBD). The following variables were collected: age, sex, history of digestive diseases, kinship and cohabitation with the index case. The relatives completed a questionnaire to identify those who met Rome I and Rome II criteria for IBS. Results The overall prevalence of IBS among the first-degree relatives of patients with IBD was 49.4% and 10% according to Rome I and Rome II criteria respectively. IBS prevalence was higher in first-degree blood relatives than in spouses of patients (Rome I: 53.1% vs 29.1%, p=0.001; Rome II: 10.8% vs 5.4%, NS). No differences were found in IBS prevalence depending on whether relatives were living with the index case or not. Conclusion IBS prevalence in first-degree relatives of patients with IBD is elevated. It is significantly greater in blood relatives, which suggests involvement of genetic and psychological factors rather than environmental factors.

Treatment with antitumor necrosis factor-alpha (anti-TNF-α) offers a significant improvement in several immune-based diseases, including Crohn's disease (CD) and psoriasis. Different cutaneous side effects have been described for anti-TNF-α therapy such as psoriasis. Previous reports showed that inhibition of TNF-α can induce over expression of cutaneous IFN-α, which in turn caused a predisposition to psoriasis. We report a 31-year-old woman with extensive CD and perianal lesions, without response to conventional treatment. She paradoxically developed a cutaneous eruption with psoriasiform morphology and distribution during treatment with both anti-TNF-α approved in Europe for CD, infliximab and adalimumab. These lesions cleared after topical application of corticosteroids and cessation of the anti-TNF-α treatment. Due to uneffectiveness of pharmacological treatment on disease, the patient had to undergo surgery. TNF-induced psoriasis in patients with CD is rare and has been previously documented with infliximab or adalimumab. The reason for this apparently paradoxical effect of the therapy is still unclear. This is the first case of psoriasis induced first by infliximab and later by adalimumab in the same CD patient. We would like to review and to draw attention about psoriasis as a cutaneous side effect with anti-TNF-α treatments.

Background Ustekinumab is a fully human monoclonal antibody against IL-12/23. Ustekinumab induced clinical response and maintained higher rate of response than placebo in patients with Crohn's disease (CD). This study aims to assess the effectiveness and safety of ustekinumab in refractory patients with CD in real-life practice. Methods Consecutive patients with CD who were treated with subcutaneous ustekinumab between March 2010 and December 2014 were retrospectively included in a multicenter open-label study. Clinical response was defined by Harvey-Bradshaw index score and assessed after the loading doses, 6, 12 months, and last follow-up. Results One hundred sixteen patients were included, with a median follow-up of 10 months (interquartile range: 5-21). Clinical response after loading ustekinumab was achieved in 97/116 (84%) patients. The clinical benefit at 6, 12 months, and at the end of the follow-up was 76%, 64%, and 58%, respectively. Dose escalation was effective in 8 of 11 (73%) patients. Perianal disease also improved in 11 of 18 (61%) patients with active perianal fistulae. The initial response to ustekinumab and previous use of more than 2 immunosuppressant drugs were associated with a clinical response to ustekinumab maintenance therapy. In contrast, previous bowel resection predicted a long-term failure with ustekinumab. Adverse events were reported in 11 (9.5%) patients, but none required ustekinumab withdrawal. Conclusions Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.

Resumen Antecedentes Hay una informacion limitada respecto al uso optimo de los inmunosupresores tiopurinicos en la enfermedad inflamatoria intestinal, sin que este completamente clarificada su posologia, eficacia y toxicidad. Objetivo Evaluar la evolucion clinica y los efectos adversos de los inmunosupresores tiopurinicos en condiciones de practica clinica (efectividad) y las posibles variables asociadas. Metodos Los datos se obtuvieron de una base de datos de pacientes con enfermedad de Crohn y colitis ulcerosa que iniciaban tratamiento inmunosupresor con azatioprina o mercaptopurina con un identico seguimiento preestablecido. Se definieron los conceptos de remision para cada indicacion, recidiva y toxicidad, y se analizaron las posibles variables clinicas, biologicas y demograficas (analisis multivariante) relacionadas. Resultados Un total de 150 cursos de tratamiento se evaluaron en 126 pacientes. En 118 cursos en los que la indicacion fue la induccion de la remision clinica, esta se alcanzo en el 62% de los pacientes y se mantuvo durante una media de 52 meses. La enfermedad perianal fue la unica variable que se asocio con una peor respuesta. En el 34% de los cursos se detectaron efectos adversos y estos fueron la principal causa de retirada del farmaco. La dosis plena de inicio (odds ratio [OR] = 4,26; intervalo de confianza [IC] del 95%, 1,12-16,32) y el cotratamiento con infliximab (OR = 5,6; IC del 95%, 1,17-27,1) se asociaron significativamente con una mayor retirada del farmaco por efectos adversos. Conclusiones Algunas variables fenotipicas y farmacologicas (posologia y cotratamientos) pueden tener una notable influencia en el perfil de efectos secundarios y, por tanto, en la efectividad de los inmunusupresores tiopurinicos en la enfermedad inflamatoria intestinal.