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BACKGROUND: Optimal thresholds for golimumab concentrations during maintenance for important outcomes are lacking. AIM: The aim of the study was to investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC. METHODS: This multicentre, cross-sectional study included UC patients on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy. RESULTS: Fifty-two patients were included. Median golimumab trough concentrations (µg/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p = 0.047), combined clinical-biochemical remission (PMS =2 + faecal calprotectin

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.

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 COVID-19 pandemic has forced major changes in the care of patients with inflammatory bowel disease (IBD). The articles by El Hajra et al. and Fernández Álvarez el al. show the modifications in patient management that were performed during the state of alarm in Spain.

Background A significant percentage of patients treated with ustekinumab may lose response. Our aim was to evaluate the short-term efficacy and safety of intravenous re-induction with ustekinumab in patients with Crohn’s disease who have lost the response to the treatment. Methods This is a retrospective, observational, multicenter study. Treatment efficacy was measured at week 8 and 16; clinical remission was defined when the Harvey-Bradshaw Index was ≤4 points, and clinical response was defined as a decrease of ≥3 points in the index compared with the baseline. Adverse events and treatment decisions after re-induction were also collected. Results Fifty-three patients from 13 centers were included. Forty-nine percent had previously failed to respond to 2 biological treatments, and 24.5% had failed to respond to 3. The average exposure time to ustekinumab before re-induction was 17.7 ± 12.8 months. In 56.6% of patients, the administration interval had been shortened to every 4 to 6 weeks before re-induction. At week 8 and 16 after re-induction, 49.0% (n = 26) and 43.3% (n = 23), respectively, were in remission, whereas 64.1% (n = 34) and 52.8% (n = 28) had a clinical response. Patients who achieved remission at week 16 had lower C-reactive protein levels than those who did not respond (2.8 ± 1.6 vs 12.5 ± 9.5 mg/dL; P = 0.001). No serious adverse events related to re-induction were observed. Conclusion Intravenous re-induction with ustekinumab is an effective and safe strategy that recovers the response in approximately half of the patients with refractory Crohn’s disease who experience a loss of response. Re-induction can be attempted before switching out of the therapy class.

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-naive, IBD patients in the real life clinical practice. Methods: a retrospective, multicentric study was performed in five Spanish hospitals. Consecutive IBD, biologic-naive patients from an historic cohort who initiated O-IFX from January 2013 were compared with biologic-naive 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-naive 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.

Autoimmune liver diseases can overlap resulting in a new entity, phenotypically different from those pathologies that converge, and that demonstrates the complexity of our immune system. Sequential overlap syndrome is the consecutive presentation, separated by a variable period of time, of two liver autoimmune diseases, mostly autoimmune hepatitis and primary biliary cholangitis. This syndrome constitutes a challenge both in its diagnosis and in its treatment given the exceptional nature of its presentation. The theory of a mosaic of autoimmunity is proposed to describe this phenomenon.

ObjectiveTo estimate COVID-19 infection incidence rate with severe affectation (requiring hospitalization) in patients with biological treatment due to rheumatoid arthritis (RA), psoriatic arthritis (PsA), spondyloarthritis (SpA), psoriasis (Ps), and inflammatory bowel disease (IBD) and compare it with incidence rate in the general population.MethodsRetrospective observational study based on information provided by two administrative databases. One of these two databases contains information on all patients seen in our hospital and diagnosed with COVID-19 infection between March 4th 2020 and April 26th 2020. The other database contains data from patients seen at Rheumatology, Dermatology and Digestive Departments in our hospital who are currently receiving biological therapy. We calculated the crude and age and sex adjusted incidence in both groups. To compare both groups we calculated the Incidence Rate Ratio.ResultsThere was a total of 2,182 patients with COVID-19 requiring hospitalization. Four patients out of a total of 797 patients receiving biological therapy had contracted COVID-19 and required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 1.41%, and it was 0.50% among the group receiving biological therapy. Rates adjusted by age and sex in the biological group was 0.45% (CI95% 0.11-4.13). The IRR of the group receiving biological therapy compared to the general population was 0.39 (CI95% 0.14-1, p=0.049).ConclusionFindings suggest that prior use of biological therapy does not associate with severe manifestations of COVID-19, and it is likely to have a protective effect against them when compared to the general population.Key MessagesWhat is already known about this subject?Covid-19 susceptibility in patients with immune-mediated disorders and receiving treatment with biological therapy is unknown.What does this study add?Severe manifestation incidence rate in patients with immune-mediated disorders receiving biological therapy treatment is not increased when compared to the general population.Biological therapies might protect patients from presenting severe COVID-19 manifestations.How might this impact on clinical practice?These data could be used for current recommendations regarding management of patients receiving biological therapies.Mini AbstractThe objective of this study is to analyze the incidence rate of severe COVID-19 requiring hospital care for patients receiving biological therapy and to compare it to the general population. Patients treated with biological therapy have crude and adjusted incidence rates under those of the general population.Statement of Human and Animal RightsThis article does not contain any studies involving human participants or animals that were performed by the authors. For this type of study, formal consent was therefore not required.

INTRODUCTION: Patients with Crohn's disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR. METHODS: Multicenter, retrospective, study of patients with Crohn's disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a Rutgeerts score < i2, respectively. RESULTS: A total of 179 patients were included, 83 were treated with infliximab and 96 with adalimumab. Median time on anti-TNF therapy at the last endoscopic assessment was 31 months (interquartile range, 13-54). Endoscopic improvement was observed in 61%, including 42% who achieved endoscopic remission. Concomitant use of thiopurines and treatment with infliximab were associated with endoscopic improvement (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.04-4.46; P = 0.03, and OR 2.34, 95% CI 1.18-4.62; P < 0.01, respectively) and endoscopic remission (OR 3.16, 95% CI 1.65-6.05; P < 0.01, and OR 2.01, 95% CI 1.05-3.88; P = 0.04, respectively) in the multivariable logistic regression analysis. These results were confirmed in a propensity-matched score analysis. DISCUSSION: In patients with endoscopic POR, anti-TNF agents improve mucosal lesions in almost two-thirds of the patients. In this setting, concomitant use of thiopurines and use of infliximab seem to be more effective in improving mucosal lesions.

Aim To assess the likelihood of detecting latent tuberculosis infection [LTBI] by the positive conversion of a serial tuberculin skin test [TST] at 1 year in inflammatory bowel disease [IBD] patients with negative baseline two-step TST. Methods In this multicentre prospective cohort study, we evaluated rate and predictors of conversion of TST at 1 year in patients with negative baseline TST. We also evaluated management of patients who had a positive TST at baseline or a conversion at 1 year. In all patients we assessed TB cases occurring during follow-up. Results Of the 192 IBD patients receiving anti-tumour necrosis factor [TNF] and 220 IBD controls not receiving anti-TNF, 35 [8.5%, 95% CI 5.7-11.3] had positive conversion (median TST induration 13 mm, interquartile range [IQR] 9-16). Ten anti-TNF cohort patients [5.2%, 95% CI 2.5-9.5] versus 25 controls [11.4%, 95% CI 7.5-16.3] had TST conversion [p = 0.029]. In multivariate analysis, conversion was associated with smoking habit (odds ratio [OR] 2.19, 95% CI 1.08-3.97; p = 0.028). Anti-TNF-treated patients had a lower conversion rate [OR 0.41, 95% CI 0.20-0.83; p = 0.013]. The likelihood of conversion correlates with fewer immunosuppressive therapies between baseline TST and TST at 1 year [p = 0.042]. One case of active TB [isoniazid-resistant strain] occurred in a patient with positive baseline TST receiving anti-TNF [0.05 events/100 patient-years]. Conclusions Serial TST at 1 year can detect LTBI in IBD patients receiving anti-TNF therapy with negative baseline TST. Serial TST seems to be advisable to reduce the risk of TB cases associated with inability to detect LTBI in pre-treatment screening.

The impact of prior anti-TNF use on “real-life” outcomes of adalimumab therapy in ulcerative colitis (UC) is not well known. 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. 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. 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-naive patients had significantly lower adjusted rates of adalimumab failure (hazard ratio [HR] 0.65; p

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

Background and aims: The aims of this study were to evaluate the frequency of entero-urinary fistulas in a cohort of Crohn’s disease (CD) patients and to analyse the outcomes of medical and surgical therapy. Methods: This multicentre retrospective study included all CD patients with entero-urinary fistulas diagnosed by the presence of clinical symptoms and confirmed at surgery or by radiological or endoscopic techniques. We evaluated outcomes of medical and surgical therapy. We defined remission as absence of clinical symptoms with a radiological confirmation of fistula closure. Cox regression analysis was performed to evaluate factors predictive of achieving remission without need for surgery. Results: Of 6081 CD patients screened, 97 had entero-urinary fistulas (frequency 1.6%). Seventy-five percent of fistulas occurred in men. After a median follow-up of 91 months, 96% of patients were in sustained remission. Thirty-three patients (35%) received anti-tumour necrosis factor (TNF) therapy. Of these, 45% achieved sustained remission (median follow-up 35 months) without needing surgery. More than 80% of patients required surgery, which induced remission (median follow-up 101 months) in 99% of them. Only the use of anti-TNF agents was associated with an increased rate of remission without need for surgery (hazard ratio 0.23, 95% confidence interval 0.12–0.44; p < 0.001). Conclusion: In this large cohort of CD patients, the frequency of entero-urinary fistulas was lower than previously described. More than 80% of patients required surgery, and in all but one of them surgery induced sustained remission. In a selected subgroup of patients, anti-TNF may induce long-term fistula remission and radiographic closure, making it possible to avoid surgery.

BACKGROUND AND AIMS: This study sought to determine the prevalence of malnutrition in patients with inflammatory bowel disease, to analyse the dietary beliefs and behaviours of these patients, to study their body composition, to evaluate their muscular strength and to identify the factors associated with malnutrition in these patients. METHODS: This was a prospective, multicentre study. Crohn's disease and ulcerative colitis patients from 30 Spanish centres, from the outpatient clinics, were included. A questionnaire of 11 items was applied to obtain data from patients' dietary behaviour and beliefs. Patients who accepted were evaluated to assess their nutritional status using Subjective Global Assessment and body mass index. Body composition was evaluated through bioelectrical impedance. RESULTS: A total of 1271 patients were included [51% women, median age 45 years, 60% Crohn's disease]. Of these, 333 patients underwent the nutritional evaluation. A total of 77% of patients declared that they avoided some foods to prevent disease relapse. Eighty-six per cent of patients avoided some foods when they had disease activity because of fear of worsening the flare. Sixty-seven per cent of patients modified their dietary habits after disease diagnosis. The prevalence of malnutrition was 16% [95% confidence interval = 12-20%]. In the multivariate analysis, history of abdominal surgery, active disease and avoidance of some foods during flares were associated with higher risk of malnutrition. CONCLUSIONS: The prevalence of malnutrition in inflammatory bowel disease patients was high. We identified some predictive factors of malnutrition. Most of the patients had self-imposed food restrictions, based on their beliefs.

To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response.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.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.Adalimumab is effective and safe for the management of CD, even in refractory cases to infliximab.

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.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 them3 months before conception. Statistical comparisons and multivariate analysis were carried out with the generalized estimating equations model.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 needed1 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).Our data do not support the practice of routinely recommending to male patients that they interrupt thiopurines when wanting to conceive.

Background Low baseline serum hepatitis C virus (HCV)-RNA and clearance of viraemia at week 4 with pegylated interferon (pegIFN) plus ribavirin therapy predict sustained virological response (SVR) and enable a shorter duration of therapy in patients with chronic hepatitis C. It is unclear whether this applies to HIV/HCV-co-infected patients. Patients and methods In the Peginterferon Ribavirin ESpana COinfection (PRESCO) trial, 389 co-infected patients received pegIFN-alpha2a 180 microg/week plus ribavirin 1000-1200 mg/day. Patients with HCV-2/3 were treated for 6 or 12 months, whereas patients with HCV-1/4 were treated for 12 or 18 months. For each genotype, baseline HCV-RNA and rapid virological response (RVR), defined as under 50 IU/ml HCV-RNA at week 4, were evaluated as predictors of SVR in an 'on-treatment' analysis. Results Overall, SVR was achieved by 193 patients (49.6%), 68/191 (35.6%) with genotype 1, 110/152 (72.4%) with genotypes 2/3 and 15/46 (32.6%) with genotype 4. RVR was the best predictor of SVR regardless of HCV genotype. Only for HCV-1 patients, baseline HCV-RNA less than 500 000 IU/ml was also associated with SVR. In HCV-3 patients RVR had a positive predictive value (PPV) for SVR of 90%, with treatment for 24 or 48 weeks. The PPV of SVR for patients with RVR was 69% for HCV-1 and 83% for HCV-4. Conclusion Undetectable HCV-RNA at week 4 is the best predictor of curing chronic hepatitis C in HCV/HIV-co-infected patients. In HCV-1 patients, baseline HCV-RNA also predicts response. HIV patients with HCV-3 and RVR may permit shortening therapy duration to only 24 weeks of pegIFN plus 1000-1200 mg ribavirin.

Background and aims: P atients with inflammatory bowel disease [IBD] are at increased risk for developing some types of neoplasia. Our aims were to determin the risk for cancer in patients with IBD and to describe the relationship with immunosuppressive therapies and clinical management after tumor diagnosis. Methods: R etrospective, multicenter, observational, 5-year follow-up, cohort study. Relative risk [RR] of cancer in the IBD cohort and the background population, therapeutic strategies, and cancer evolution were analyzed. Results: A total of 1 45 cancers were diagnosed in 133 of 9100 patients with IBD (global cumulative incidence 1.6% vs 2.4% in local population; RR = 0.67; 95% confidence interval [CI]: 0.57–0.78). Patients with IBD had a significantly increased RR of non-melanoma skin cancer [RR = 3.85; 2.53– 5.80] and small bowel cancer [RR = 3.70; 1.23–11.13]. After cancer diagnosis, IBD treatment was maintained in 13 of 27 [48.1%] patients on thiopurines, in 2 of 3 on methotrexate [66.6%], none on anti-TNF-α monotherapy [n = 6] and 4 of 12 [33.3%] patients on combined therapy. Rate of death and cancer remission during follow-up did not differ [p > 0.05] between patients who maintained the treatment compared with patients who withdrew [5% vs 8% and 95% vs 74%, respectively]. An association between thiopurines [p = 0.20] or anti-TNF-α drugs [p = 0.77] and cancer was not found. Conclusions: P atients with IBD have an increased risk for non-melanoma skin cancer and small bowel cancer. Immunosuppresive therapy is not related to a higher overall risk for cancer or worse tumor evolution in patients who maintain these drugs after cancer diagnosis.

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.

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.

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.

Objetivo: valorar el efecto de la pentoxifilina (un potente inhibidor del factor de necrosis tumoral alfa) en la supervivencia, en la hemodinámica sistémica y portal y en la función cardiaca en la cirrosis alcohólica avanzada. Diseño: estudio aleatorizado, doble-ciego, controlado con placebo. Contexto: estudio unicéntrico utilizando grupos de pacientes en paralelo para comparar pentoxifilina y placebo. Pacientes: se incluyeron 24 pacientes con cirrosis alcohólica (8 en estadio B de Child-Pugh y 16 en estadio C de Child-Pugh). Intervención: los pacientes fueron aleatorizados a recibir pentoxifilina (400 mg, 3 veces al día, n = 12) o placebo (n = 12) durante 4 semanas. Determinaciones: el objetivo principal fue la supervivencia a corto/largo plazo. Los objetivos secundarios fueron observar beneficios hemodinámicos (mejoría en la función cardiaca y/o en el índice de resistencias vasculares sistémicas o disminución de la presión portal). Resultados: la presión portal y la función cardiaca no se modificaron y no hubo diferencias en la supervivencia a corto y largo plazo entre los grupos tratados y placebo. Los índices de resistencia vascular sistémica y cardiaco cambiaron en el grupo de pentoxifilina (de 1.721 ± 567 a 2.082 ± 622 Din.seg ¹ cm-5 m-2 y de 4,17 ± 1,4 a 3,4 ± 0,9 lm-2, p = 0,05). Conclusiones: aunque la pentoxifilina parece producir algún beneficio hemodinámico a corto plazo en pacientes con cirrosis alcohólica avanzada, no tiene efecto sobre la tasa de supervivencia, la función cardiaca ni sobre la presión portal en estos pacientes.

Macro-creatine-kinases are isoenzymes of creatinine-kinases (CK). They have been classified in two types: type 1 (CK bound to an immunoglobulin) and type 2 (an oligomeric mitochondrial CK). CK type 1 has been found in patients with ulcerative colitis (UC) but not in Crohn's disease (CD). However, there are no studies evaluating macro-creatinkinase prevalence in inflammatory bowel disease (IBD). We included 159 consecutive patients (72 UC, 85 CD; 2 indeterminate colitis). Creatin-kinase total activity and isoenzymes activities were determined. Twelve (16.7%) patients with UC and one of the two patients with indeterminate colitis had serum macro-creatinkinase type 1 while no CD patients displayed this macromolecule (P < 0,001). Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio were calculated for ulcerative colitis versus Crohn's disease diagnosis, being 16.7, 98.9, 92.3, 59, 14.5, and 0.84% respectively. There was no correlation with age, gender, time from diagnosis, associated diseases, concomitant medication or disease activity. In conclusion our data suggests that the presence of macro-CK in IBD favors the diagnosis of ulcerative colitis. Further studies are necessary to understand the significance of this finding in a subset of patients with IBD.

Adalimumab Dose Escalation Is Effective for Managing Loss of Response in Ulcerative Colitis Carlos Taxonera, Eva Iglesias Flores, Fernando Munoz, Marta Calvo, Manuel Barreiro-de Acosta, David Busquets, Xavier Calvet, Antonio Rodriguez, R. Pajares, Javier P. Gisbert, Pilar Lopez-Serrano, Jose Lazaro Perez-Calle, Angel Ponferrada Diaz, Cristobal De la Coba, Fernando Bermejo, Maria Chaparro, Cristina Alba, David Olivares, Ignacio Fernandez-Blanco

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.

We intended to analyze the influence of Helicobacter pylori eradication on the clinical evolution of patients with chronic idiopathic urticaria.The evolution of dermatological symptoms after eradication was studied in a group of 55 patients previously diagnosed with chronic idiopathic urticaria who were infected by Helicobacter pylori.There was a partial or complete improvement in 74.6% (CI 95%, 61-85%) of studied patients. We could not demonstrate a statistically significant influence of sex, age or endoscopic lesions on the clinical evolution of urticaria after eradication.These results suggest a possible usefulness of Helicobacter pylori eradication in some patients with chronic idiopathic urticaria. Controlled and randomized studies are necessary to confirm it.

(p = 0.013) during follow-up of the cohort. No statistical significance was obtained regarding the need for biological therapy or surgery. Statistically significant association between smoking and need for hospitalization was also found in CD (p = 0.004). There is also a significant association between younger age at diagnosis and biological therapy need (p = 0.022) and between B3 pattern and need for immunomodulatory therapy (p = 0.009). The B1 pattern was associated with less hospitalization (p = 0.049) and less need for surgery (p = 0.018). For UC no statistically significant association between the independent variables of the patients, disease phenotype and therapeutic needs was found. Conclusions: In our hospital area of southern Spain incidence rates are similar to other areas of southern Europe. However Greater incidence of Crohn’s disease with respect to UC is described. Crohn’s disease requires more aggressive therapy than CU (immunomodulators and surgery). An early age at diagnosis is associated with greater need for biologic therapy.

analyzed by gene array, immunofluorescence, flow cytometry and thymidine incorporation. Results Anti-TNF induced regulatory macrophages displayed increased numbers of autophagosomes as well as an increased expression of autophagy related transcripts including atg5, atg7, atg9 and atg16l2, suggesting induction of autophagy by IFX treatment. Of all donors, 7 were homozygously carrying the CD associated risk allele, 14 were heterozygous and 7 were homozygous for the WT allele. The number of CD14+ regulatory macrophages correlated significantly with the number of WT alleles present in each individual culture, with the largest number of macrophages found in cultures containing 3 or 4 WT alleles (2 WT donors or 1 WT and 1 heterozygous). Similarly, expression of CD206, which is associated with the immunosuppressive function of macrophages, positively correlated with the number of WT alleles present. To confirm the functional consequences of these findings, IFX mediated suppression of T cell proliferation was determined. Again, the level of suppression correlated significantly with the number of WT alleles present in the respective donor combinations. Conclusion Induction of regulatory macrophages by IFX is associated with induction of autophagy. In vitro, the number and function of IFX induced macrophages correlated with the number of WT alleles for the autophagy related gene ATG16L1. This suggests that an intact autophagy pathway is important for effectiveness of anti-TNF therapy.

One UC patient (9.1%) had synchronous adenocarcinomas at rectum and descending colon. The histologies of CRCs were as follows; moderately differentiated adenocarcinoma in seven (36.8%), mucinous adenocarcinoma in five (26.3%), poorly differentiated adenocarcinoma in three (15.8%), well differentiated adenocarcinoma in three (15.8%), and signet ring cell carcinoma in one (5.3%). The stage distribution of cancer was as follows; I in one (5.3%), II in seven (36.8%), III in three (15.8%) and IV in eight (42.1%). The cumulative risks of CRC at 10 years after UC, CD, and IBD diagnosis were 0.4%, 0.4%, and 0.4%, respectively. They were 4.9%, 6.6% and 5.5%, respectively after 20 years (Figure 1).

P152 Role of inflammatory bowel disease in fertility of male patients P. Valer1 *, A. Algaba1, E. Nieto2, I. Guerra1, M. Chaparro3, P. Lopez-Serrano4, E. Quintanilla5, B. Piqueras1, A. Bermejo1, J.P. Gisbert3, A. Paez6, F. Bermejo1. 1Hospital Universitario de Fuenlabrada, Gastroenterology, Fuenlabrada, Spain, 2Hospital Universitario de Fuenlabrada, Laboratory, Fuenlabrada, Spain, 3Hospital Universitario de La Princesa, and Instituto de Investigacion Sanitaria Princesa (IP), Madrid Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Gastroenterology, Madrid, Spain, 4Hospital Universitario Fundacion Alcorcon, Gastroenterology, Alcorcon, Spain, 5Hospital Severo Ochoa, Gastroenterology, Leganes, Spain, 6Hospital Universitario de Fuenlabrada, Urology, Fuenlabrada, Spain