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Background and Aims: Familial inflammatory bowel disease (IBD) history is a controversial prognostic factor in IBD. We aimed to evaluate the impact of a familial history of IBD on the use of medical and surgical treatments in the biological era., Methods: Patients included in the prospectively maintained ENEIDA database and diagnosed with IBD after 2005 were included. Familial forms were defined as those cases with at least one first-degree relative diagnosed with IBD. Disease phenotype, the use of biological agents, or surgical treatments were the main outcomes., Results: A total of 5263 patients [2627 Crohn's disease (CD); 2636 ulcerative colitis (UC)] were included, with a median follow-up of 31 months. Of these, 507 (10%) corresponded to familial forms. No clinical differences were observed between familial and sporadic IBD forms except a lower age at IBD diagnosis and a higher rate of males in familial forms of UC. In CD, the proportions of patients treated with thiopurines (54.4% vs 46.7%; P = .015) and survival time free of thiopurines (P = .009) were lower in familial forms. No differences were found regarding the use of biological agents. Concerning surgery, a higher rate of intestinal resections was observed in sporadic CD (14.8% vs 9.9%, P = .027). No differences were observed in UC., Conclusions: In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.

Cervical cancer (CC) is the fourth most common cancer affecting women worldwide. The risk of women immunosuppressed due to AIDS or organ transplantation is well documented, as most cases are caused by persistent human papillomavirus (HPV) infection and immunosuppression can prevent clearing HPV. Although European guidelines advise that inflammatory bowel disease (IBD) women under immunosuppression should be screened for CC as regularly as high-risk patients, quality evidence is lacking in our country. We performed a retrospective case-control (2020-2021) study to analyse the risk factors associated with the appearance of low-grade (LSIL) or high-grade (HSIL) squamous intraepithelial cervical lesions in patients with IBD. We included all women aged 21-65 years , followed up at the University Hospital Fundación Alcorcón (Spain). Cases were defined as those patients with abnormalities in cervical cytology, while the control group consisted of the rest of the women. Disease characteristics, treatments and epidemiological data (smoking habit, sexual behaviour and reproductive history) were obtained. We documented the evolution of abnormalities over time and compare data between women under immunosuppressive treatment or not.

Background and Objectives: inflammatory bowel disease (IBD) has a major impact on psychological well-being. This condition is associated with a high level of anxiety and mood disorders, but stress prevalence and how an individual copes with IBD have not been sufficiently explored. The objective of this study was to assess the impact of the disease on psychological disorders and to identify coping strategies used by patients with IBD, as well as to analyze the relationship between these variables and sociodemographic and clinical variables., Methods: a cross-sectional prospective study was performed including 126 consecutive patients. Those with psychiatric conditions prior to the onset of the IBD were excluded. Independent variables were measured using a sociodemographic and clinical questionnaire. The patients completed the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale (PSS) and the BRIEF COPE questionnaire. Quality of life was measured using the nine-item IBD Quality of Life (IBDQ-9)., Results: the final cohort comprised 100 patients (37 with ulcerative colitis and 63 with Crohn's disease). The prevalence rates of the variables of stress, anxiety and depression were high (44 %, 24 % and 14 %, respectively). Stress and depression were higher in females (p < 0.05), without differences regarding other sociodemographic and clinical variables. Moreover, higher levels of anxiety and depression were found to be associated with stress and dysfunctional coping strategies (p < 0.01)., Conclusions: patients with IBD, particularly women, have high rates of psychological disorders. Those with anxiety and depression presented more stress and used more dysfunctional strategies. These conditions must be considered for a multidisciplinary management.

Introduction: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines., Methods: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced., Results: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls., Conclusion: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset., (© 2024 S. Karger AG, Basel.)

Introduction: The internet is emerging as a source of information for patients with inflammatory bowel disease (IBD). However, it is not always reliable and may cause anxiety. We aim to assess patients' information habits and patients' and professionals' perceptions of a national website integrated as an educational resource for the IBD unit. Methods: Patients aged 18-65 years, comfortable with the internet, and attending follow-ups at participating IBD units (March-June 2019) and their professionals were invited to evaluate a recommended website through an online survey. Results: Three hundred eighty-nine patients and 95 professionals completed the survey. The internet ( n  = 109; 27.4%) was the second preferred source of information after the health care team ( n  = 229; 57.5%). Eighty percent of patients searched the internet for information on their disease and 28.6% did so at least once a week ( n  = 114), especially newly diagnosed ones (<2 years). Patients valued a website recommended by their professional ( n  = 379; 95.2%) and endorsed by the National Working Group ( n  = 377; 94.7%). They would attend online educational initiatives on the website ( n  = 279; 70.1%) and complete periodical surveys to improve its usefulness ( n  = 338; 84.9%). According to IBD professionals, this type of website is the best patient source of supplementary information ( n  = 76; 80%) and they "prescribe" it to most patients (67.0 ± 25.2%), especially the newly diagnosed patients (52.7 ± 26.5%). It effectively integrates routine face-to-face education ( n  = 95; 100%). Conclusions: Patients of IBD units, especially newly diagnosed ones, appreciate a trusted e-Health resource to back up professional information. The favorable opinion of patients and professionals will allow its use in training interventions.

Introduction: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice., Methods: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score., Results: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation., Discussion: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported., (Copyright © 2023 by The American College of Gastroenterology.)

Background and Aims: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD., Methods: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54., Results: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]., Conclusions: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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

Background and Aims: Immunomediated adverse events [IAEs] are the most frequently reported infliximab [IFX]-related adverse events. Combination therapy may reduce their incidence, although this strategy is not recommended in elderly patients. We aimed to compare the rates of IFX-related IAEs and loss of response [LOR] in elderly and younger patients., Methods: Adult patients in the ENEIDA registry who had received a first course of IFX therapy were identified and grouped into two cohorts regarding age at the beginning of treatment [over 60 years and between 18 and 50 years]. The rates of IAEs and LOR were compared., Results: In total, 939 patients [12%] who started IFX over 60 years of age and 6844 [88%] below 50 years of age were included. Elderly patients presented a higher proportion of AEs related to IFX [23.2% vs 19%; p = 0.002], infections [7.1% vs 4.3%; p < 0.001] and neoplasms [2.2% vs 0.5%; p < 0.001]. In contrast, the rates of IAEs [14.8% vs 14.8%; p = 0.999], infusion reactions [8.1% vs 8.1%; p = 0.989], late hypersensitivity [1.3% vs 1.2%; p = 0.895], paradoxical psoriasis [1% vs 1.5%; p = 0.187] and drug-induced lupus erythematosus [0.6% vs 0.7%; p = 0.947] were similar in elderly and younger patients. LOR rates were also similar between the two groups [20.5% vs 19.3%; p = 0.438]. In the logistic regression analysis, IFX monotherapy, extraintestinal manifestations and female gender were the only risk factors for IAEs, whereas IFX monotherapy, extraintestinal manifestations and Crohn's disease were risk factors for LOR., Conclusions: Elderly patients with inflammatory bowel disease have a similar risk of developing IFX-related IAEs and LOR to that of younger patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-ץ-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18−20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50−0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66−0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20−22%] vs. 14% [95% CI 13−16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM.

Background: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain., Methods: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients., Results: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses., Conclusions: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe., Competing Interests: AG has served as speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Tillotts Pharma, Chiesi and Otsuka Pharmaceutical. ER has provided scientific advice/participated in medical meetings/received research funding from/received payment for presentations and advice from: MSD, Schering-Plow, Ferring, Abbvie, Takeda, Janssen, Fresenius Kabi, Pfizer. IV has served as a speaker, or has received research or education funding from Abbvie, MSD, Pfizer, Takeda, Janssen, Tillotts Pharma, Ferring and Shire Pharmaceuticals. MM has served as speaker or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Biogen, Tillotts Pharma, Chiesi and Adacyte. JPG has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene, Gilead/Galapagos, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, and Vifor Pharma. YZ has received support for conference attendance, speaker fees, research support and consulting fees from Abbvie, Adacyte, Almirall, Amgen, Dr. Falk, FAES Pharma, Ferring, Janssen, MSD, Otsuka, Pfizer, Shire, Takeda and Tillots. XC has received grants for research from Abbvie, MSD, Vifor fees for advisory boards form Abbvie, MSD, Takeda, Pfizer, Janssen and VIFOR and has given lectures for Abbvie, MSD, Janssen, Pfizer, Takeda, Shire and Allergan. FB has served as a speaker, a consultant and advisory member for or has received research funding from MSD, Abbvie, Takeda, Janssen, Pfizer, Biogen, Amgen, Ferring, Faes Farma, Tillotts Pharma, Falk Pharma, Chiesi, Gebro Pharma, Vifor Pharma. MM-M has served as speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Shire Pharmaceuticals and Otsuka Pharmaceutical. MR has served as speaker, consultant or advisory member for MSD, Abbvie, Pfizer, Takeda, Janssen, Ferring and Chiesi. MP has served as speaker or has received research funding from Abbvie, Takeda and Janssen. IR-L has received financial support for traveling and educational activities from or has served as an advisory board member for MSD, Pfizer, Abbvie, Takeda, Janssen, Tillotts Pharma, Shire Pharmaceuticals, Roche, Celltrion, Faes Farma, Ferring, Dr. Falk Pharma, Otsuka Pharmaceutical and Adacyte. Financial support for research from Tillotts Pharma. RL has served as a speaker, or has received research or education funding from MSD, Abbvie, Pfizer, Takeda, Janssen and Dr. Falk. LA has served as speaker, or has received research or education funding from MSD, Abbvie, Kern Pharma, Ferring, FaesFarma, Shire Pharmaceuticals, Pfizer, Takeda, Janssen, Tillotts Pharma, and Otsuka Pharmaceutical. FA-A has served as speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Tillotts Pharma, Chiesi and Dr. Falk. LR has served as a speaker, or has received education funding from MSD, Abbvie, Adacyte, Takeda, Pfizer, Janssen and Ferring. MB-d has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gillead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma. ED has served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Gilead, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, Tillots, Thermofisher. RF has served as a speaker, or has received research or education funding or advisory fees from AbbVie, Janssen, Takeda, Adacyte Therapeutics, Sanofi, GlaxoSmithKline, Almirall. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gutiérrez, Zapater, Ricart, González-Vivó, Gordillo, Olivares, Vera, Mañosa, Gisbert, Aguas, Sánchez-Rodríguez, Bosca-Watts, Laredo, Camps, Marín-Jiménez, Zabana, Martín-Arranz, Muñoz, Navarro, Sierra, Madero, Vela, Pérez-Calle, Sainz, Calvet, Arias, Morales, Bermejo, Fernández-Salazar, Van Domselaar, De Castro, Rodríguez, Muñoz-Villafranca, Lorente, Rivero, Iglesias, Herreros, Busquets, Riera, Martínez-Montiel, Roldón, Roncero, Hinojosa, Sierra, Barrio, De Francisco, Huguet, Merino, Carpio, Ginard, Muñoz, Piqueras, Almela, Argüelles-Arias, Alcaín, Bujanda, Manceñido, Lucendo, Varela, Rodríguez-Lago, Ramos, Sempere, Sesé, Barreiro-de Acosta, Domènech and Francés.)

Background: A recently registered device containing 80 mg of adalimumab (ADA) allows an alternative dose escalation regimen with ADA 80 mg every other week (EOW) given as a single subcutaneous injection instead of 40 mg every week. The ADASCAL study evaluated the preferences and satisfaction of inflammatory bowel disease (IBD) patients after switching their ADA regimen from 40 mg weekly to 80 mg EOW given with a single-dose pen., Methods: In this multicentre cross-sectional study, patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW completed the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), a four-item questionnaire [a Likert-type 5-point scale for preferences, two closed questions for convenience and a 100-point visual analogue scale (VAS) to assess which escalated ADA regimen patients would prefer to continue] and two Health-Related Quality of Life (HRQoL) questionnaires: the generic European Quality of Life-5 Dimensions (EQ-5D) and disease-specific Spanish version of the Inflammatory Bowel Disease Questionnaire (SIBDQ-9)., Results: In total, 77 patients (64 Crohn's disease and 13 ulcerative colitis) were included. The TSQM score showed a notably high global satisfaction [83.4, standard deviation (SD) = 14.1] of patients with ADA 80 mg EOW given with a single-dose pen, with high TSQM scores for individual components: effectiveness (77.6, SD = 16.9), convenience (83.7, SD = 14.5) and side effects (86.1, SD = 23.4). Most of the patients (74%) preferred the ADA EOW regimen (59.7% had strong preference, 14.3% slight preference). ADA EOW interferes less with daily activity (59.7%) and with travel plans (81.8%). Most patients (77%) would prefer to continue with ADA EOW (mean VAS score of 84.7, SD = 24.1, where 100 indicates a preference for ADA EOW). Patients reported high HRQoL scores on both the EQ-5D (72.3, SD = 20.1) and SIBDQ-9 (75.1, SD = 14.7)., Conclusion: IBD patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW reported a higher preference for the EOW regimen and therefore most decided to continue with a single self-injection EOW., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. C.T. has served as a speaker, consultant and advisory board member for or has received research funding from MSD, AbbVie, Pfizer, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Galapagos and Tillots. M.P.M.-M. has served as speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Pfizer, Kern Pharma, Takeda, Janssen, Shire Pharmaceuticals and Otsuka Pharmaceutical. M.B.-d.-A. has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gilead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma. I.V. has served as a speaker, consultant and advisory member for and has received funding from MSD, AbbVie, Pfizer, Ferring, Shire Pharmaceuticals, Takeda and Janssen. R.L. has served as a speaker, or has received research or education funding from MSD, AbbVie, Pfizer, Takeda, Janssen and Dr. Falk Pharma. P.V. has served as a speaker, consultant or advisory member for MSD, AbbVie, Ferring, Faes Farma, Takeda and Janssen. B.C. has served as a speaker, consultant and advisory board member for MSD, AbbVie, Ferring, Shire, Takeda and Janssen. R.F.-I. has served as a speaker, consultant and advisory board member for MSD, AbbVie, Pfizer, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Adacyte and Tillots. J.L.P.C. has served as a speaker, consultant and advisory board member for MSD, AbbVie, Ferring, Faes Farma, Takeda and Janssen. C.A. has served as a speaker for Janssen and has prepared promotional material for Falk Pharma. These activities were not related to the present work. The remaining authors have no conflicts of interest to declare., (© The Author(s), 2021.)

Background and Aims: The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life., Methods: Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16., Results: A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection., Conclusions: Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known., Aims: To assess the risk of relapse in the long-term after anti-TNF discontinuation., Methods: This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease., Results: This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11-14). The cumulative incidence of relapse was 50% (95% CI = 47-53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment., Conclusions: A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies., (© 2021 John Wiley & Sons Ltd.)

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

Background and Aims: Although commonly used in inflammatory bowel disease [IBD], thiopurines frequently cause intolerance, and switching to a second thiopurine has only been reported in some small series. Ours aims in this study were to evaluate the safety of switching to a second thiopurine in a large cohort, and to assess the impact of age on tolerance., Methods: Adult IBD patients from the ENEIDA registry, who were switched to a second thiopurine due to adverse events [excluding malignancies and infections], were identified. At the beginning of thiopurine treatment, patients were divided by age into two groups: 18-50 and over 60 years of age. The rate and concordance of adverse events between the first and second thiopurines, treatment intolerance, and persistence with the second thiopurine were evaluated., Results: A total of 1278 patients [13% over 60 years of age] were switched to a second thiopurine. At 12 months, the cumulative probability of switch intolerance was 43%, and persistence with treatment was 49%. Independent risk factors of switch intolerance were age over 60 years (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.07-2.07; p = 0.017) , previous gastrointestinal toxicity [OR 1.4; 95% CI 1.11-1.78; p = 0.005], previous acute pancreatitis [OR 6.78; 95% CI 2.55-18.05; p <0.001], and exposure to the first thiopurine <6 months [OR 1.59; 95% CI 1.14-2.23; p = 0.007]., Conclusions: In a large series in clinical practice, switching to a second thiopurine proved to be a valid strategy. Tight monitoring of elderly IBD patients switching to a second thiopurine because of adverse events is recommended., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients., Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent., Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug., Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies., Methods: PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool., Results: In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50-139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7-19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9-5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1-9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39-53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC., Conclusions: PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Anti-tumor necrosis factor agents (anti-TNFs) are efficacious at preventing the postoperative recurrence (POR) of Crohn disease, as demonstrated in 2 randomized controlled trials. However, real-life data for infliximab or adalimumab in this setting are scarce. Our aim was to assess both the efficiency of anti-TNFs at preventing early POR of Crohn disease in clinical practice and the associated risk factors for POR., Methods: Patients in whom anti-TNFs were prescribed for the prevention of POR within 3 months after ileocolonic resection and who had an endoscopic assessment within 18 months were identified from the ENEIDA registry. Clinical and endoscopic features were collected within 18 months after surgery., Results: In total, 152 patients were included (55 treated with infliximab, 97 with adalimumab, and 39% with concomitant immunosuppressants). Anti-TNF treatment was started after a median time of 29 days (IQR 13-44) after surgery. Eighty-two percent of patients had at least one risk factor for POR, and 82% had been exposed to anti-TNFs before the index surgery. Overall, 34% had endoscopic POR (as defined using a Rutgeerts endoscopic score > i1); 14% had advanced endoscopic POR (>i2); and 20% had clinical POR, with no differences between infliximab and adalimumab. In the multivariate analysis, only perianal disease (odds ratio 2.73, 95% confidence interval [CI] 1.26-5.91) and rectal involvement (odds ratio 2.79, 95% CI 1.09-7.14) were independent predictors of endoscopic POR., Conclusions: In clinical practice, anti-TNFs for the prevention of POR of Crohn disease are frequently used in patients experienced with anti-TNFs and with concomitant immunosuppressants. The efficacy of infliximab and adalimumab for POR prevention is similar and in accordance with the results obtained in randomized controlled trials., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Effectiveness of vedolizumab in real world clinical practice is unknown., Aim: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD)., Methods: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response., Results: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent., Conclusions: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice., (© 2018 John Wiley & Sons Ltd.)

Background: The impact of prior anti-TNF use on "real-life" outcomes of adalimumab therapy in ulcerative colitis (UC) is not well known., Aim: To compare the influence of prior anti-TNF use on the outcomes of adalimumab maintenance treatment in UC patients. We also assessed the effectiveness of adalimumab dose escalation., Methods: This retrospective multicenter cohort study included consecutive UC who advanced to an adalimumab maintenance regimen. Patients in whom adalimumab was discontinued prior to week eight of treatment were excluded. The co-primary efficacy endpoints were the cumulative probabilities of adalimumab failure-free survival and colectomy-free survival. We also assessed the need for and the effectiveness of adalimumab dose escalation., Results: Of 184 UC on maintenance treatment with adalimumab, 116 (63%) had previous anti-TNF use. After a median follow-up of 23 months (interquartile range 13-49), 112 patients (60%) maintained corticosteroid-free clinical response. Sixty-nine patients (37%) had adalimumab failure, and 22 (12%) needed colectomy. Anti-TNF-naïve patients had significantly lower adjusted rates of adalimumab failure (hazard ratio [HR] 0.65; p < 0.001), adalimumab dose escalation (HR 0.35; p = 0.002), and need for colectomy (HR 0.26; p < 0.004). Seventy-six patients (41%) needed dose escalation after secondary loss of response, and 47% of these regained response after escalation. Short-term response after escalation was identified as a significant predictor of colectomy avoidance (HR 0.53; p = 0.007)., Conclusions: In this "real-life" cohort of UC patients on maintenance treatment with adalimumab, anti-TNF-naïve patients had significantly better long-term outcomes. Adalimumab dose escalation enabled recovery of response in nearly half of patients.

Objectives: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed., Methods: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included., Results: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe., Conclusions: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Background: Anti-TNF treatment is effective for Crohn's disease (CD); however, some patients did not achieve remission with these drugs., Aims: To evaluate the short-term effectiveness of a second anti-TNF in CD patients who did not achieve remission with the first one and to assess its durability., Methods: Patients who did not achieve remission with their first anti-TNF were included. The short-term response of the second anti-TNF was assessed, the long-term response was evaluated in patients who achieved remission (Kaplan-Meier). Cox-regression was performed to identify predictors of loss of efficacy., Results: In all, 118 CD patients received a second anti-TNF after primary failure of the first. The first anti-TNF was discontinued because of non-response in 54% of patients and partial response in 46%. Fifty-one percent of patients achieved remission in the short-term. The probability of remission was lower in patients for whom the drug indication was perianal disease (OR=0.3, 95% CI=0.1-0.7, P=0.005). The dose was increased in 33% of patients, and 37% achieved/regained remission. The probability of maintaining remission was 76%, 68% and 64% at 12, 18 and 24 months, respectively., Conclusions: Approximately half of the patients achieved remission with a second anti-TNF after primary failure of the first, this strategy was less effective in patients with perianal disease., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the 2-year incidence of new immune-mediated inflammatory diseases (spondylarthritis, uveitis, psoriasis) in the cohort of patients with inflammatory bowel disease (IBD) included in the AQUILES study., Materials and Methods: Over a 2-year period, 341 patients with IBD (53% women, mean age 40 years) diagnosed with Crohn's disease (60.5%), ulcerative colitis (38.1%) and indeterminate colitis (1.4%) were followed up. New diagnoses made during follow-up were based on reports of the corresponding specialists (rheumatologists, ophthalmologists, and dermatologists)., Results: A total of 22 new diagnoses of immune-mediated inflammatory diseases were established in 21 patients (cumulative incidence of 6.5%, 95% confidence interval [CI] 3.7-9.2, incidence rate of 26 cases per 10,000 patient-years). Most diagnoses were new cases of spondylarthritis (n=15). The cumulative incidence of new diagnoses of immune-mediated inflammatory diseases was similar in patients with Crohn's disease (5.8%, 95% CI 3.4-9.9) and in patients with ulcerative colitis (7.7%, 95% CI 4.2-13.6). On multivariate analysis, the incidence of new immune-mediated inflammatory diseases was significantly associated with a family history of IBD (odds ratio=3.6, 95% CI 1.4-9.4) and the presence of extraintestinal manifestations of IBD (odds ratio=1.8, 95% CI .7-5.2)., Conclusions: In patients with IBD, the incidence of new immune-mediated inflammatory diseases at 2 years of follow-up was 6.5%. These diseases were more frequent in patients with extraintestinal manifestations of IBD and a family history of IBD., (Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.)

Currently immunosuppressive and biological agents are used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus (HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to pre-emptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.

Substantial proportion of Crohn's disease (CD) patients shows no response or a limited response to treatment with infliximab (IFX) and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11) reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350) who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276* G/rs3014866* C/rs724781* C/rs3006488* A; P = 0.05); G0S2 (rs4844486* A/rs1473683* T; P = 0.15); TNFAIP6 (rs11677200* C/rs2342910* A/rs3755480* G/rs10432475* A; P = 0.10); and IL11 (rs1126760* C/rs1042506* G; P = 0.07). These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway.

Infliximab (IFX) is a valid treatment for Crohn's disease (CD), but a relevant percentage of patients do not benefit from this therapy. In the Japanese population, the response to IFX was associated with markers in the TNF receptor superfamily 1A (TNFRSF1A) and 1B (TNFRSF1B) genes. We aimed to replicate the association previously described in the Japanese population and to ascertain the role of TNF receptors as modulators of the response to IFX. We studied 297 white Spanish CD patients with a known response to IFX: 238 responders and 59 primary nonresponders. Four single nucleotide polymorphisms (SNPs) were analyzed: rs767455 in TNFRSF1A and rs1061622, rs1061624, and rs3397 in TNFRSF1B. Comparisons between groups were performed with chi-square tests or the Fisher's exact test. Different features (sex, age, disease duration, smoking among others) were evaluated as possible confounding factors. No significant association was found between the studied TNFRSF1A polymorphisms and response to IFX. In the TNFRSF1B gene, the haplotype rs1061624&#95;A-rs3397&#95;T was significantly increased in nonresponders: p = 0.015, OR = 1.78, 95% CI 1.09-2.90; and an increased frequency of rs1061622&#95;G carriers was observed in patients with remission: p = 0.033 vs nonresponders and p = 0.023 vs patients with a partial response. Our results support a role of TNFRSF1B gene variants in the response to IFX in CD patients., (Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Hepatitis B virus (HBV) is a very common infection worldwide. Its reactivation in patients receiving immunosuppression has been widely described as being associated with significant morbidity and mortality unless anti-viral prophylaxis is administered. Treatment in inflammatory bowel disease (IBD) patients has changed in recent years and immunosuppression and biological therapies are now used more frequently than before. Although current studies have reported an incidence of hepatitis B in inflammatory bowel disease patients similar to that in the general population, associated liver damage remains an important concern in this setting. Liver dysfunction may manifest in several ways, from a subtle change in serum aminotransferase levels to fulminant liver failure and death. Patients undergoing double immunosuppression are at a higher risk, and reactivation usually occurs after more than one year of treatment. As preventive measures, all IBD patients should be screened for HBV markers at diagnosis and those who are positive for the hepatitis B surface antigen should receive antiviral prophylaxis before undergoing immunosuppression in order to avoid HBV reactivation. Tenofovir/entecavir are preferred to lamivudine as nucleos(t)ide analogues due to their better resistance profile. In patients with occult or resolved HBV, viral reactivation does not appear to be a relevant issue and regular DNA determination is recommended during immunosuppression therapy. Consensus guidelines on this topic have been published in recent years. The prevention and management of HBV infection in IBD patients is addressed in this review in order to address practical recommendations.

The patient with inflammatory bowel disease will be predisposed to numerous infections due their immune status. It is therefore important to understand the immune and serologic status at diagnosis and to put the patient into an adapted vaccination program. This program would be applied differently according to two patient groups: the immunocompromised and the non-immunocompromised. In general, the first group would avoid the use of live-virus vaccines, and in all cases, inflammatory bowel disease treatment would take precedence over vaccine risk. It is important to individualize vaccination schedules according to the type of patient, the treatment used and the disease pattern.In addition, patient with inflammatory bowel disease should be considered for the following vaccines: varicella vaccine, human papilloma virus, influenza, pneumococcal polysaccharide vaccine and hepatitis B vaccine.

Objectives: The safety of thiopurines and anti-tumor necrosis factor-α (TNF-α) drugs during pregnancy remains controversial, as the experience with these drugs in this situation is limited. Our aim is to assess the safety of thiopurines and anti-TNF-α drugs for the treatment of inflammatory bowel disease (IBD) during pregnancy., Methods: Retrospective, multicenter study in IBD patients. Pregnancies were classified according to the therapeutic regimens during pregnancy or during the 3 months before the conception: non-exposed group, pregnancies exposed to thiopurines alone (group A), and pregnancies exposed to anti-TNF-α drugs (group B). An unfavorable Global Pregnancy Outcome (GPO) was considered if pregnancy developed with obstetric complications in the mother and in the newborn., Results: A total of 187 pregnancies in the group A, 66 pregnancies in the group B, and 318 pregnancies in the non-exposed group were included. The rate of unfavorable GPO was different among the three groups (31.8% in non-exposed group, 21.9% in group A, and 34.8% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). The rate of pregnancy complications was similar among the three groups (27.7% in non-exposed, 20.9% in group A, and 30.3% in group B). The rate of neonatal complications was different among the three groups (23.3% in non-exposed group, 13.9% in group A, and 21.2% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). In the multivariate analysis, the treatment with thiopurines (odds ratio = 0.6; 95% confidence interval = 0.4-0.9, P = 0.02) was the only predictor of favorable GPO, whereas maternal age >35 years at conception was the only predictor of unfavorable GPO. The treatment with anti-TNF-α drugs was not associated with an unfavorable GPO., Conclusion: The treatment with thiopurines and anti-TNF-α drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn.

Background: Methotrexate is useful in inflammatory bowel disease (IBD), but its role is secondary because of its limited experience and a supposedly unfavorable safety profile., Aim: To describe the efficacy and safety of methotrexate in a long-term real clinical practice., Methods: Retrospectively reviewed records of IBD patients treated with methotrexate in eight hospitals of Madrid (Spain)., Results: A total of 77 patients were included (80% Crohn's disease); 94% received methotrexate because of steroid dependency. Overall, 82% of the patients initially responded (28% remission). Eighty-eight percent of the patients followed maintenance treatment for a mean of 17 (range: 1-108) months. Forty percent of the patients lost response at a mean of 57 weeks after starting methotrexate. No statistically significant differences were found in the response rates in terms of the disease type, route of administration, or the Montreal Classification category. The mean methotrexate cumulative dose was 1108 mg (range: 25-6480). The main adverse events included 10 cases of gastrointestinal symptoms, four of myelotoxicity, and 10 of abnormal liver function tests, and led to methotrexate withdrawal in four (5%) patients. Transient elastography, performed in 46 patients, detected six additional cases with significant fibrosis and normal liver function tests., Conclusion: Methotrexate is useful in inducing a response in IBD, although its efficacy decreases frequently through the follow-up. Although methotrexate seems safe in the long term, in addition to biochemical controls, a more accurate method to detect liver damage should be considered.

Aim: Anti-tumor necrosis factor (TNF)-alpha agents are widely used for the treatment of both inflammatory bowel disease (IBD) and psoriasis. Psoriatic skin lesions induced by anti-TNF have been described in patients with IBD. We report a case series of psoriasis induced by anti-TNF agents in IBD patients., Methods: Systematic analysis of cases of psoriasis induced by anti-TNF in an IBD patient cohort in tertiary hospitals of Madrid., Results: A total of 21 of 1294 patients with IBD treated with anti-TNF-alpha agents developed drug-induced psoriasis (cumulative incidence 1.62%; 95% CI 1.06%-2.47%): 14 patients with infliximab and 7 with adalimumab; seventeen with Crohn's disease, 4 with ulcerative colitis. The onset of skin lesions varied in a wide range of time (after a mean 13±8 doses). The most frequent site of skin lesions was the limbs (62%) followed by the trunk (48%) and the scalp (43%). The psoriasis phenotypes were plaque psoriasis (57%), scalp (14%), palmoplantar pustulosis (14%), pustular generalized psoriasis (5%), guttate (5%) and inverse (5%). Four patients interrupted the anti-TNF treatment, and that led to the complete regression of lesions in 1 of them. The other 17 patients were maintained on anti-TNF therapy and managed with topical steroids., Conclusion: Psoriatic lesions can be induced by anti-TNF drugs. Plaque psoriasis on the extremities and trunk were the most frequent presentations in our series. Topical steroid treatment is effective in most patients. Anti-TNF discontinuance may be reserved for patients with severe psoriasis or patients without response to topical therapy., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Methotrexate is an effective treatment for inflammatory bowel disease (IBD). However, long-term treatments have been associated with the development of liver fibrosis. FibroScan® is a noninvasive, safe, and effective technique to evaluate liver fibrosis., Aim: To evaluate the presence of significant liver fibrosis by transient elastography (FibroScan®) in IBD patients treated with methotrexate., Methods: Cross-sectional study including IBD patients treated with methotrexate from different hospitals. Clinical and analytical data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan®. The cutoff value for significant liver fibrosis (according to METAVIR) was F ≥ 2: 7.1 kPa. Results. In the study, 46 patients were included, 30 women (65%), with a mean age of 43 ± 10 years. 31 patients had Crohn's disease (67.4%), 13 ulcerative colitis (28.3%), and 2 indeterminate colitis (4.3%). The mean cumulative dose of methotrexate was 1242 ± 1349 mg, with a mean treatment duration of 21 ± 24 months. The mean value of liver stiffness was 4.7 ± 6.9 kPa. There were 35 patients (76.1%) with F01, 8 patients (17.4%) with F = 2, and 3 patients with F ≥ 3 (6.5%). There were no differences in liver stiffness depending on sex, age, type of IBD, or cumulative dose of methotrexate., Conclusions: (1) Development of advanced liver fibrosis in IBD patients treated with methotrexate is exceptional. (2) There were no differences in liver stiffness depending on the type of IBD or the cumulative dose of methotrexate. (3) FibroScan® may be potentially useful for evaluation and follow-up of liver fibrosis in methotrexate-treated patients.

Introduction: The response of Crohn's disease (CD) to infliximab is initially good, although a loss of efficacy is observed over time. Dose escalation has been recommended in such cases., Aims: To study the response to an intensified infliximab regimen in patients with CD; and to evaluate the adverse effects associated with intensification of therapy and identify predictors of loss of response., Methods: We performed a retrospective multicenter survey of all patients with CD who had been treated with at least the 3 induction doses of standard infliximab therapy, and for whom treatment had to be intensified due to loss of response. We analyzed the efficacy of the intensified regimen., Results: Thirty-three patients were included. After the first intensification dose, 79% of patients had a clinical response (33.5% complete response, 45.5% partial response). In the long term, 83%, 69%, 47%, and 29% of patients who had an initial response to the intensification maintained the response at 6, 12, 18, and 36 months, respectively. The loss of efficacy after escalation was 43% per patient-year of follow-up. One patient had an infusion reaction after 36 doses. One patient developed a herpes zoster infection., Conclusions: A high proportion of patients whose dose of infliximab is increased due to loss of efficacy respond initially. However, nearly half lose the response after one year. The safety profile of an intensified infliximab regimen is good., (Copyright © 2011. Published by Elsevier B.V.)

Objective: To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response., Methods: Multicenter retrospective survey of all CD patients treated with adalimumab in 9 hospitals of the Madrid area (Spain). Univariate and multivariate analysis of predictors of response was performed., Results: 174 patients included (50% males) with a median follow-up of 40 weeks. 30% had active perianal fistulizing disease at the beginning of the therapy with adalimumab. 59% had been previously treated with infliximab, being the lost of response (42.2%) the most frequent cause of withdrawal of the drug. 33% of patients needed dose escalation from every-other week to every week. The median time for this dose escalation was 33 weeks (range 2-120). The percentages of complete response at 4 weeks, 6 months and end of follow-up were 63, 70 and 63% in luminal disease and 49, 50 and 41% in perianal disease respectively. The prevalence of adverse events was 18% (most frequent was: 5 abscesses) causing the withdrawal of the drug in 21% of them., Conclusions: Adalimumab is effective and safe for the management of CD, even in refractory cases to infliximab., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Objective: Environmental factors have been implicated in the etiology of inflammatory bowel disease (IBD), but evidence for the hygiene hypothesis is unclear. We investigated the relationship between early-life infection-related exposures and risk of IBD., Patients and Methods: A hospital-based case-control study was carried out. A total of 124 cases of Crohn's disease (CD) and 146 of ulcerative colitis (UC) were compared with 235 and 278 well-matched control subjects, respectively. A multi-item questionnaire on familial history of IBD, childhood circumstances and familial socioeconomic status was carried out., Results: In a multivariate model, living in urban areas (odds ratio (OR) 4.58 (95% CI 2.17-10)), high educational level (OR 1.83 (95% CI 14-2.95)) and social status (OR 1.68 (95% CI 1.2-2.35)) were risk factors for CD, whereas childhood respiratory infections (OR 0.35 (95% CI 0.23-0.52)) and gastroenteritis (OR 0.55 (95% CI 0.36-0.85)) were protective factors. Living in urban areas (OR 4.6 (95% CI 2.29-9.9)), a high educational level (OR 10.3 (95% CI 2.54-42.1)) and social status (OR 2.042 (95% CI 1.31-3.17)) were also risk factors for UC, whereas respiratory infections (OR 0.42 (95% CI 0.29-0.6)) and gastroenteritis (OR: 0.6 (95% CI 0.42-0.86)) were protective factors. Appendectomy (OR 0.173 (95% CI 0.06-0.52)) and current smoking (OR 0.75 (95% CI 0.59-0.96)) were also protective for UC., Conclusion: These results further support the hypothesis that better living conditions during childhood are associated with an increased risk for IBD, and reinforce the negative association between smoking and appendectomy and the risk of UC.

Objectives: Immunomodulators are used as maintenance treatment of inflammatory bowel disease (IBD). Data regarding their possible effects in the course of pregnancy when the father is exposed at the time of conception are limited., Methods: To evaluate the outcomes of pregnancies of which the fathers were exposed to thiopurines at the time of conception. A series of male patients followed in seven IBD clinics in Madrid, Spain, was studied. Any exposure to thiopurines during the 3 months preceding conception was considered significant. Controls were pregnancies fathered by patients who either had never been treated with thiopurines or had interrupted them >3 months before conception. Statistical comparisons and multivariate analysis were carried out with the generalized estimating equations model., Results: There were 46 conceptions in the exposed group (mercaptopurine 9, azathioprine 37) and 84 in the control group. In the exposed group, there were more Crohn's patients (82.6% vs. 53.6%), the duration of the disease was longer (median: 8 vs. 5 years), fathers were slightly older (mean: 34.2 vs. 32.7 years), and there were fewer patients on mesalamine (15.2% vs. 47.6%). Otherwise, baseline characteristics were similar in both groups. There were no significant differences regarding unsuccessful pregnancies-namely, spontaneous abortions, ectopic pregnancies, anembryonic pregnancies, or fetal deaths (10.9% exposed group vs. 13.1% control group; odds ratio (OR): 0.79, confidence interval (CI): 0.22-2.85), preterm births (4.3% vs. 2.4%; OR: 1.3, CI: 0.22-7.61), low birth weight (6.5% vs. 6%; OR: 1.06, CI: 0.25-4.54), or congenital malformations (2.2% vs. 2.4%; OR: 0.82, CI: 0.08-9). No infant neoplasms were detected. The proportion of conceptions that needed >1 year to be achieved was higher in the exposed group, but this was not statistically significant (15.2% vs. 8.3%; OR: 1.92, CI: 0.54-6.88). Multivariate analysis was carried out for unsuccessful pregnancies and fertility impairment, and it showed that, although mesalamine exposure confounded the effect of the exposure to thiopurines on these outcomes, this effect was still nonsignificant (respectively, OR: 0.49, CI: 0.17-1.44; OR: 2.82, CI: 0.7-11.38)., Conclusions: Our data do not support the practice of routinely recommending to male patients that they interrupt thiopurines when wanting to conceive.

Background: Pulse oximetry is a widely accepted procedure for ventilatory monitoring during gastrointestinal endoscopy, but this method provides an indirect measurement of the respiratory function. In addition, detection of abnormal ventilatory activity can be delayed, especially if supplemental oxygen is provided. Capnography offers continuous real-time measurement of expiratory carbon dioxide., Objective: We aimed at prospectively examining the advantages of capnography over the standard pulse oximetry monitoring during sedated colonoscopies., Patients and Methods: Fifty patients undergoing colonoscopy were simultaneously monitored with pulse oximetry and capnography by using two different devices in each patient. Several sedation regimens were administered. Episodes of apnea or hypoventilation detected by capnography were compared with the occurrence of hypoxemia., Results: Twenty-nine episodes of disordered respiration occurred in 16 patients (mean duration 54.4 seconds). Only 38% of apnea or hypoventilation episodes were detected by pulse oximetry. A mean delay of 38.6 seconds was observed in the events detected by pulse oximetry (two episodes of disturbed ventilation were simultaneously detected by capnography and pulse oximetry)., Conclusions: Apnea or hypoventilation commonly occurs during colonoscopy with sedation. Capnography is more reliable than pulse oximetry in early detection of respiratory depression in this setting.

Introduction: The incidence of inflammatory bowel disease (IBD) varies widely according to geographical area and has been reported to have increased in the last few years. No data are available on the current incidence of this disease in Madrid (Spain)., Aim: to determine the incidence of inflammatory bowel disease in the area of influence of University Hospital Fundación Alcorcón (Madrid), and to compare our results with those from other Spanish and European series., Patients and Methods: A prospective, population-based study was performed to determine the incidence of IBD in the area of University Hospital Fundación Alcorcón in Madrid between 2003 and 2005. Total population: 213,587 inhabitants (177,490 older than 14 years). Crude rates and age- and sex-specific rates adjusted to the European standard population were calculated. A retrospective study (1998-2003) was also performed., Results: A total of 69 cases were diagnosed -Crohn s disease (CD): 35, ulcerative colitis (UC): 33, indeterminate colitis: 1- in the prospective period. Crude rates of CD and UC were 7.92 and 7.47 cases/100,000 inhabitants/year, respectively (the population aged 0-14 years). Specific rates were 8.0 (95% CI, 7.03-8.97) and 7.47 (95% CI, 6.5-8.4), respectively. Mean age at diagnosis was 31.02+/- 10.76 and 39.91+/-16.19 years for CD and UC, respectively. Incidence in the retrospective study was 7.13 and 6.22 cases/100,000 inhabitants/year, respectively for CD and UC., Conclusions: The incidence of CD and UC in Madrid has increased in the last decades, with rates close to those in northern European countries for CD, higher than those recently published in Spanish prospective studies and similar to those previously described in Spain and southern countries for UC. Rates were higher in the prospective period than in the retrospective one.

Background: The aim was to evaluate the efficacy and tolerance of oral and intravenous iron treatment in anemic inflammatory bowel disease (IBD) patients, considering both hematological and quality-of-life outcomes., Methods: We performed a prospective multicenter study in IBD patients with iron deficiency anemia. Patients having hemoglobin >10 g/dL were prescribed oral ferrous sulfate. If hemoglobin <10 g/dL, intravenous (sucrose) iron was administered. Oral iron-intolerant patients were changed to intravenous treatment. Clinical (Truelove/Harvey-Bradshaw), hematological (response defined as hemoglobin normalization), and quality-of-life (shortened CCVEII-9 questionnaire) evaluations were performed at baseline and at 3 and 6 months., Results: 100 IBD patients (59 Crohn's disease, 41 ulcerative colitis) were included. Mean basal hemoglobin levels were 10.8 +/- 1.3 g/dL (range, 6.6-12.9). Seventy-eight patients received oral treatment and 22 intravenous iron. Hemoglobin normalization was achieved in 86% of patients: 89% with oral, and 77% with intravenous iron. An IBD activity increase was not demonstrated in any patient. Four patients (5.1%) showed oral iron intolerance leading to discontinuation of treatment. No adverse events were reported for intravenous iron. Hemoglobin correlated with CCVEII-9 (P < 0.001). The CCVEII-9 score increased in patients who normalized hemoglobin levels in 3 months (from 58 +/- 9 to 73 +/- 10) or 6 months (54 +/- 9, 68 +/- 12, and 74 +/- 10) (P < 0.001)., Conclusions: Oral iron treatment is effective and well tolerated in most IBD patients, and does not exacerbate the symptoms of the underlying IBD. Intravenous iron, on the other hand, is an effective and safe alternative treatment for iron deficiency anemia in more severely anemic or intolerant patients. Anemia correction with iron treatment is associated with a relevant improvement in the patients' quality of life.

Background: The purpose of the study was to determine the role of fecal calprotectin and lactoferrin in the prediction of inflammatory bowel disease relapses, both in patients with ulcerative colitis (UC) and Crohn's disease (CD), in a large, long-term, follow-up study., Methods: The prospective multicenter study included CD and UC patients who had been in clinical remission for 6 months. At baseline, patients provided a single stool sample for calprotectin and lactoferrin determination. Follow-up was 12 months in patients showing no relapse and until activity flare in relapsing patients., Results: In all, 163 patients (89 CD, 74 UC) were included. Twenty-six patients (16%) relapsed during follow-up. Calprotectin concentrations in patients who suffered a relapse were higher than in nonrelapsing patients (239 +/- 150 versus 136 +/- 158 microg/g; P < 0.001). Relapse risk was higher in patients having high (>150 microg/g) calprotectin concentrations (30% versus 7.8%; P < 0.001) or positive lactoferrin (25% versus 10%; P < 0.05). Fecal calprotectin (>150 microg/g) sensitivity and specificity to predict relapse were 69% and 69%, respectively. Corresponding values for lactoferrin were 62% and 65%, respectively. The area under the receiver operating characteristic curve to predict relapse using calprotectin determination was 0.73 (0.69 for UC and 0.77 for CD). Better results were obtained when only colonic CD disease or only relapses during the first 3 months were considered (100% sensitivity). High fecal calprotectin levels or lactoferrin positivity was associated with clinical relapse in Kaplan-Meier survival analysis, and both fecal tests were associated with relapse in the multivariate analysis., Conclusions: Fecal calprotectin and lactoferrin determination may be useful in predicting impending clinical relapse-especially during the following 3 months-in both CD and UC patients.

Background: Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis., Aim: To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease., Methods: Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid (n = 5073)., Results: A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n = 46, mesalazine (mesalamine) n = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3-9.3; P = 0.012) and Crohn's disease (CD) (OR 5.8 95% CI: 1.6-20.6; P = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP (n = 1477) (OR 5.2 95% CI: 1.8-14; P = 0.002)., Conclusions: The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD.

Background: Efficacy of infliximab in Crohn's disease (CD) showed by randomized controlled trials must be confirmed in clinical practice. We aimed to evaluate efficacy and safety of infliximab in CD patients of the Madrid area, looking for clinical predictors of response., Methods: Multicenter retrospective survey of all CD patients treated with infliximab in 8 University hospitals of the Madrid area (Spain) with a minimum follow up of 14 wks., Results: 169 patients included (48%males, mean age 39 +/- 12 yrs). 64% of them had perianal disease. 82% were under immunosuppressants. 1,355 infliximab infusions administered (mean 8, range 1-30). 90% response rate and 48% remission rate were obtained with induction therapy. 73% followed maintenance treatment, and 78% of them maintained or improved the response after a mean follow up of 28 months (range 3.5-86). 24 patients lost response during the follow up, after a mean of 41 wks (range 6-248). Only the prescription of maintenance therapy was predictive factor for favourable response (p < 0.01). 17 infusion reactions were reported (10% of the patients, 1.2% of the infusions; only one case was severe) and were the cause of treatment withdrawal in 7 patients. Co-treatment with immunosuppressive drugs and maintenance infliximab therapy were protective factors for infusion reactions (p < 0.05). Other adverse events occurred in 26% of the patients, and were cause of treatment withdrawal in 7 patients., Conclusions: Infliximab is effective and safe for CD management but concomitant immunosuppressive drugs and maintenance treatment should be prescribed to obtain the best outcome. That confirms in a real life clinical setting the favourable results obtained in randomized clinical trials.