Search

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 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.

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&rsquo, perspective on telemonitoring for IBD. Accordingly, this study aimed to adapt the TECCU telemonitoring 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 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 three focus groups involving a total of 18 patients. Three main themes emerged: (1) platform usability, (2) the communication process, and (3) platform content. All participants indicated that TECCU is easy to use, permitting continuous and personalized feedback. According to patients&acute, perspectives, the platform was adapted to foster a flexible follow-up and shared decision-making using open and safe communication networks. Many participants appreciated the educational elements and, consequently, the app was connected to reliable and continuously updated webpages. Conclusions: IBD patients valued the usability and personalized monitoring offered by the TECCU App. Improvements in the messaging system and continuously updated educational content were introduced to address patients&acute, needs and favor their engagement.

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.

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 Although electronic health interventions are considered safe and efficient, evidence regarding the cost-effectiveness of telemonitoring in inflammatory bowel disease is lacking. Objective We aimed to evaluate the cost-effectiveness and cost-utility of the Telemonitorización de la Enfermedad de Crohn y Colitis Ulcerosa (Telemonitoring of Crohn’s Disease and Ulcerative Colitis [TECCU]) Web platform (G_TECCU intervention group) for telemonitoring complex inflammatory bowel disease, compared with standard care (G_control) and nurse-assisted telephone care (G_NT intervention group). Methods We analyzed cost-effectiveness from a societal perspective by comparing the 3 follow-up methods used in a previous 24-week randomized controlled trial, conducted at a tertiary university hospital in Spain. Patients with inflammatory bowel disease who initiated immunosuppressants or biologic agents, or both, to control inflammatory activity were recruited consecutively. Data on the effects on disease activity (using clinical indexes) and quality-adjusted life-years (using the EuroQol 5 dimensions questionnaire) were collected. We calculated the costs of health care, equipment, and patients’ productivity and social activity impairment. We compared the mean costs per patient, utilities, and bootstrapped differences. Results We included 63 patients (21 patients per group). TECCU saved €1005 (US $1100) per additional patient in remission compared with G_control (95% CI €–13,518 to 3137; US $–14,798 to 3434), with a 79.96% probability of being more effective at lower costs. Compared with G_NT, TECCU saved €2250 (US $2463) per additional patient in remission (95% CI €–15,363 to 11,086; US $–16,817 to 12,135), and G_NT saved €538 (US $589) compared with G_control (95% CI €–6475 to 5303; US $–7088 to 5805). G_TECCU and G_NT showed an 84% and 67% probability, respectively, of producing a cost saving per additional quality-adjusted life-year (QALY) compared with G_control, considering those simulations that involved negative incremental QALYs as well. Conclusions There is a high probability that the TECCU Web platform is more cost-effective than standard and telephone care in the short term. Further research considering larger cohorts and longer time horizons is required. Trial Registration ClinicalTrials.gov NCT02943538; https://clinicaltrials.gov/ct2/show/NCT02943538 (http://www. webcitation.org/746CRRtDN)

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.

Background: The reported efficacy of telemedicine in patients with inflammatory bowel disease (IBD) is inconsistent among studies, and data for complex IBD are lacking. Objective: We aimed to evaluate the impact of remote monitoring using a Web system—Telemonitorizacion de la Enfermedad de Crohn y Colitis Ulcerosa or Telemonitoring of Crohn’s Disease and Ulcerative Colitis (TECCU)—as compared to standard care and telephone care on health outcomes and health care in patients with complex IBD. Methods: We performed a 3-arm randomized controlled trial. Adult patients with IBD who received immunosuppressants and biological agents were recruited from the IBD Unit of a tertiary university hospital. The patients were randomized into groups to receive remote monitoring (G_TECCU), nurse-assisted telephone care (G_NT), or standard care with in-person visits (G_control). All patients completed the study visits at baseline and at 12 and 24 weeks in addition to each type of intervention. The primary outcome was the percentage of patients in remission at 24 weeks. Secondary health outcomes were quality of life, medication adherence, adverse effects, satisfaction, and social activities. Data on the number of outpatient visits and telephone calls, emergency visits, hospitalizations, IBD-related surgeries, and corticosteroid courses were also collected. Results: A total of 63 patients were selected (21 patients in each group). During the study, 90.5% (19/21) of patients in G_control, 95.2% (20/21) in G_NT, and 85.7% (18/21) in G_TECCU were compliant to the intervention. After 24 weeks, the percentage of patients in remission was higher in G_TECCU (17/21, 81%) than in G_NT (14/21, 66.7%) and G_control (15/21, 71.4%). A higher improvement in disease activity was observed in G_TECCU than in G_control in terms of the Harvey-Bradshaw/Mayo (odds ratio=0.12, 95% CI=0.003-2.162, P=.19) and Harvey-Bradshaw/Walmsley (odds ratio=0.11, 95% CI=0.004-1.55, P=.13) indexes. Improvement in disease activity was associated with a larger reduction in fecal calprotectin values in G_TECCU compared to G_control (estimated intervention effect: odds ratio=–0.90; 95% CI=–1.96 to 0.16, P=.11). All completers adhered to treatment in G_TECCU. In addition, the quality of life, social activities, and satisfaction improved in all 3 groups. Although the number of outpatient visits and telephone calls was lower in G_TECCU than in G_NT and G_control, the safety profile was similar in all 3 groups. Conclusions: This pilot clinical trial suggests that the TECCU Web-based system is a safe strategy for improving health outcomes in patients with complex IBD and reducing the use of health care resources. Trial Registration: ClinicalTrials.gov NCT02943538; https://clinicaltrials.gov/ct2/show/NCT02943538 (Archived by WebCite at http://www.webcitation.org/746CRRtDN).

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.

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.

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 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.

Despite controversy regarding the use of granulocyte/monocyte adsorption (GMA) in inflammatory bowel disease, some studies have shown favorable outcomes when it is used in steroid-dependent patients with ulcerative colitis (UC). The mechanisms responsible for such outcomes are not well characterized, but changes in immune cell populations and cytokine levels have been suggested to play an important role. We report the cases of 3 patients with chronically active severe UC who underwent GMA due to an inadequate response to standard and rescue therapy, as well as changes to their plasma cytokine profile. All the patients presented severe UC that was only partially responsive to various immunosuppressive drugs, and they were, therefore, referred for colectomy; however, all 3 refused this option, which led to the compassionate use of GMA as a last therapeutic resort. Following GMA treatment, rapid normalization of the clinical, endoscopic and laboratory parameters was observed in all the patients. Despite having achieved a good response, most cytokines remained at high concentrations after GMA, and only two, IL-6 and IL-8, showed a clear decrease throughout the GMA sessions. In view of this outcome, we hypothesize that GMA can help to lower the inflammatory load, thereby enhancing the effect of biologic drugs. To confirm this hypothesis and explore further indications for GMA, we propose the need for research directed toward the characterization of immune cell populations and their specific cytokine production rather than global cytokine assessment.

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...

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.

To investigate the influence of thiopurines and biological drugs on the presence of small intestinal bacterial overgrowth (SIBO) in patients with inactive Crohn's disease (CD).This was a prospective study in patients with CD in remission and without corticosteroid treatment, included consecutively from 2004 to 2010. SIBO was investigated using the hydrogen glucose breath test.One hundred and seven patients with CD in remission were included. Almost 58% of patients used maintenance immunosuppressant therapy and 19.6% used biological therapy. The prevalence of SIBO was 16.8%. No association was observed between SIBO and the use of thiopurine Immunosuppressant (12/62 patients), administration of biological drugs (2/21 patients), or with double treatment with an anti-tumor necrosis factor drugs plus thiopurine (1/13 patients). Half of the patients had symptoms that were suggestive of SIBO, though meteorism was the only symptom that was significantly associated with the presence of SIBO on univariate analysis (P0.05). Multivariate analysis revealed that the presence of meteorism and a fistulizing pattern were associated with the presence of SIBO (P0.05).Immunosuppressants and/or biological drugs do not induce SIBO in inactive CD. Fistulizing disease pattern and meteorism are associated with SIBO.

The genetic analysis of ulcerative colitis (UC) has provided new insights into the etiology of this prevalent inflammatory bowel disease. However, most of the heritability of UC (>70%) has still not been characterized. To identify new risk loci for UC we have performed the first genome-wide association study (GWAS) in a Southern European population and undertaken a meta-analysis study combining the newly genotyped 825 UC patients and 1525 healthy controls from Spain with the six previously published GWAS comprising 6687 cases and 19 718 controls from Northern-European ancestry. We identified a novel locus with genome-wide significance at 6q22.1 [rs2858829, P = 8.97 × 10(-9), odds ratio (OR) (95% confidence interval, CI] = 1.12 (1.08-1.16)] that was validated with genotype data from a replication cohort of the same Southern European ancestry consisting in 1073 cases and 1279 controls [combined P = 7.59 × 10(-10), OR (95% CI) = 1.12 (1.08-1.16)]. Furthermore, we confirmed the association of 33 reported associations with UC and we nominally validated the GWAS results of nine new risk loci (P < 0.05, same direction of effect). SNP rs2858829 lies in an intergenic region and is a strong cis-eQTL for FAM26F gene, a gene that is shown to be selectively upregulated in UC colonic mucosa with active inflammation. Our results provide new insight into the genetic risk background of UC, confirming that there is a genetic risk component that differentiates from Crohn's Disease, the other major form of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a debilitating immune disorder that impairs function and health-related quality of life (HRQOL). A goal of IBD treatment is mucosal healing, but it is not known whether it achieves normalization of the patients' perception of health. This can be assessed by using a cut-off scoring threshold of the Inflammatory Bowel Disease Questonnaire-36 (IBDQ-36).To determine whether patients with Crohn's disease (CD) and ulcerative colitis (UC) in clinical remission and with mucosal healing normalize their HRQOL.This is a multicentric, prospective, observational, cross-sectional study of patients who are in stable clinical remission and having mucosal healing. Patients completed the IBDQ-36, the EuroQol-5D, and the Daily Fatigue Impact Scale fatigue questionnaires. Complete restoration of health was believed to have occurred when the global score in the IBDQ-36 was at least 209 points.A total of 115 patients (48 with CD, 67 with UC) were included. The median activity index (the Harvey-Bradshaw or the colitis activity index) was 1.0 and the median endoscopic index (Simple Endoscopic Score for Crohn's disease or Mayo) was 0. Eighty percent of the patients (79% in CD and 82% in UC patients, P=NS) normalized their HRQOL. Type of treatment was not related to normalization of HRQOL. The lack of restoration of health was significantly related to fatigue and anxiety/depression.Mucosal healing is associated with a normalization of the perception of health by most IBD patients independently of treatment. However, a significant group of patients do not achieve restoration of HRQOL, which reinforces the necessity of a global care addressed to all patient concerns to achieve patients' complete health restoration.

Summary Background : The incidence of thiopurine-induced hepatotoxicity in patients with inflammatory bowel disease varies in different studies. Aims : To assess the rate of thiopurine-induced liver toxicity in patients with inflammatory bowel disease; to determine the predictive factors and to characterize its clinical course and management. Methods : A cohort of 161 patients was prospectively followed for a median of 271 days. Hepatotoxicity was established when alanine transaminase or alkaline phosphatase plasma levels were greater than twice the upper normal limit. Results : Abnormal liver function was detected in 21 patients (13%; 95% CI: 7–18). Hepatotoxicity occurred in 16 patients (10%; 95% CI: 6–16) after a median of 85 days. In five cases, treatment was withdrawn due to hepatotoxicity. Use of corticosteroids was associated with hepatotoxicity (OR: 4.94; 95% CI: 1.01–23.98) with antitumour necrosis factor concomitant therapy showing a protective role (OR: 0.3; 95% CI: 0.1–3.1). γ-Glutamyl transferase plasma levels at the onset of hepatotoxicity showed the best predictive value for treatment withdrawal (area under the receiver operating characteristic curve: 0.95). Conclusions : The incidence of hepatotoxicity in inflammatory bowel disease patients receiving thiopurines is relevant, mainly in patients co-treated with corticosteroids. γ-Glutamyl transferase plasma level is a useful biomarker in therapy withdrawal prediction.

P090 Restoration of health in patients with inflammatory bowel disease and mucosal healing F. Casellas Jorda1 *, M. Barreiro-de Acosta2, M. Iglesias2, V. Robles1, P. Nos3, M. Aguas4, S. Riestra5, R. De Francisco5, M. Papo6, N. Borruel1. 1Hospital Vall D’Hebron, Barcelona, Spain, 2University Hospital, Santiago De Compostela, Spain, 3La Fe Hospital, Instituto De Investigacion Sanitaria, Valencia, Spain, 4La Fe Hospital, Valencia, Spain, 5Hospital Universitario Central De Asturias, Inflammatory Bowel Disease Unit, Oviedo, Spain, 6Hospital Joan XXIII, Tarragona, Spain

Background Portal-mesenteric vein thrombosis, pylephlebitis and liver abscesses are rare complications of inflammatory bowel disease (IBD). The purpose of this case report is to relate an unusual presentation of CD in order to show how conservative treatment could be an appropriate option as a bridge to the surgery, in patients with septic thrombophlebitis and multiple liver abscesses with CD. Case presentation We report a case of a 25-year-old man with Crohn's disease (CD) who developed a superior mesenteric venous thrombosis, multiple liver abscesses and pylephlebitis, diagnosed through abdominal ultrasound and an abdominal computed tomography (CT) scan. The patient was successfully treated with conservative treatment consisting of intravenous antibiotics, subcutaneous anticoagulation and percutaneous catheter drainage of liver abscesses. Conclusion We reported an unnusual case of pylephlebitis in CD. Until now this association has not been reported in adult patients at onset. We hypothesise that the infection developed as a result of mucosal disease and predisposed by corticoid therapy. Adequated management was discussed.

Background: The effect of thiopurine immunomodulators on health-related quality of life (HRQoL) in patients with inflammatory bowel disease (IBD) has been controversial. The aims were to evaluate the HRQoL in patients with IBD treated with thiopurines and assess the short- and long-term impacts of the treatment on HRQoL.Methods: Ninety-two consecutive patients who started treatment with thiopurines were prospectively included. Evaluation of HRQoL was performed at months 0, 6, and 12 using two questionnaires, the Short-Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ).Results: Baseline score of IBDQ was 4,6, range (2,31-6,84), with an impairment of the five dimensions of HRQoL compared with inactive patients. Results obtained in 8 dimensions of SF-36 showed worse HRQoL than Spanish general population. At 6 months patients had a significant improvement in overall IBDQ score -5,8 (1,58 -6,97)- and also in all IBDQ dimensions. All the 8 dimensions of SF-36 obtained a significant improvement. At twelve months score of IBDQ was 6,1, range (2,7-6,98), with improvement in all dimensions compared with baseline and 6 months. SF-36 showed a similar significant improvement in all subscales.Conclusions: Thiopurine immunomodulators alone or with other treatments have a positive and long lasting impact on HRQoL of IBD patients. © 2010 Bastida et al; licensee BioMed Central Ltd., Guillermo Bastida MD was supported by a grant from the “Fundacion para la investigación Hospital Universitario La Fe“. Ciberehd is funded by the Instituto de Salud Carlos III.