Javier Castro

Ulcerative colitis in northern Portugal and Galicia in Spain

Background: Clinical and therapeutic patterns of ulcerative colitis (UC) are variable in different world regions. The purpose of this study was to examine two close independent southern European UC populations from 2 bordering countries and observe how demographic and clinical characteristics of patients can influence the severity of UC. Methods: A cross‐sectional study was conducted during a 15‐month period (September 2005 to December 2006) based on data of 2 Web registries of UC patients. Patients were stratified according to the Montreal Classification and disease severity was defined by the type of treatment taken. Results: A total of 1549 UC patients were included, 1008 (65%) from northern Portugal and 541 (35%) from Galicia (northwest Spain). A female predominance (57%) was observed in Portuguese patients (P < 0.001). The median age at diagnosis was 35 years and median years of disease was 7. The majority of patients (53%) were treated only with mesalamine, while 15% had taken immunosuppressant drugs, and 3% biologic treatment. Most patients in both groups were not at risk for aggressive therapy. Extensive colitis was a predictive risk factor for immunosuppression in northern Portugal and Galicia (odds ratio [OR] 2.737, 95% confidence interval [CI]: 1.846–4.058; OR 5.799, 95% CI: 3.433–9.795, respectively) and biologic treatment in Galicia (OR 6.329, 95% CI: 2.641–15.166). Younger patients presented a severe course at onset with more frequent use of immunosuppressors in both countries. Conclusions: In a large population of UC patients from two independent southern European countries, most patients did not require aggressive therapy, but extensive colitis was a clear risk factor for more severe disease. (Inflamm Bowel Dis 2010)

Evaluation of adalimumab therapy in multidisciplinary strategy for perianal Crohn's disease patients with infliximab failure.

BACKGROUND Infliximab has improved the management of perianal Crohns disease, but intolerance and loss of efficacy can occur. The use of a second antibody can be less effective. OBJECTIVE Our aim was to determine if the use of adalimumab, based on a multidisciplinary strategy, can enhance outcomes for patients with fistulizing disease and infliximab failure. MATERIAL AND METHODS Sixteen patients with perianal disease and infliximab failure were treated with adalimumab. Complex fistulas were assessed using magnetic resonance imaging (MRI). Patients with severe conditions as determined by radiology were examined under anesthesia, and seton placement was performed when appropriate. Setons were removed when external discharge had ceased and there was no radiological evidence of fistula activity. RESULTS Nine patients (56%) underwent MRI. Setons were inserted in seven (43%). The baseline perianal disease activity index (PDAI) decreased after 4 weeks and remained at similar levels 24 and 48 weeks after treatment. The complete response rate was 50% after four weeks and 87.5% of these patients remained in remission after 48 weeks of treatment. CONCLUSIONS For patients with Crohns perianal fistulas and infliximab failure, adalimumab as a multidisciplinary approach to management, using MRI to guide surgical drainage when necessary, results in a favourable response and low recurrence rate.

Clinical, biological, and endoscopic responses to adalimumab in antitumor necrosis factor-naive Crohn's disease: predictors of efficacy in clinical practice.

Background and aims Endoscopic healing and clinical remission are important parameters to evaluate therapeutic efficacy in Crohn’s disease. The aim of this study was to investigate the clinical effectiveness of adalimumab in terms of clinical and endoscopic response and to identify predictors of efficacy in clinical practice. Materials and methods A prospective analysis was carried out of 68 antitumor necrosis factor-naive Crohn’s disease patients treated with adalimumab for 2 years. Clinical and endoscopic response was assessed using the Harvey–Bradshaw index and the Simple Endoscopic Score for Crohn’s disease, respectively. Results Adalimumab treatment was associated with clinical remission in 76.6, 90.6, and 87.5% of patients at 6, 12, and 24 months. Loss of efficacy occurred in 17.6% of cases after 24 months of therapy. Clinical remission with normal C-reactive protein at 2 months or with endoscopic response at 6 months was predictive of better outcomes. Mucosal healing rates were 17.2, 44.7, and 39.5% and endoscopic responses were 55.1, 76.6, and 76.3% at the respective time points. Mucosal healing was higher in the early treatment group than in the group with disease of at least 5 years’ duration (64.7 vs. 19.1%, P=0.004). Inflammatory phenotype showed a higher percentage of mucosal healing (70%) than stricturing (29.4%) or penetrating (27.3%) disease. Conclusion Adalimumab was effective in providing sustained clinical remission. In patients in clinical remission, the C-reactive protein level at 2 months, endoscopic response at 6 months, or inflammatory phenotype and short disease duration could be considered as good predictors of efficacy.

Influence of urban/rural and coastal/inland environment on the prevalence, phenotype, and clinical course of inflammatory bowel disease patients from northwest of Spain: a cross-sectional study

Background Data on the influence of rural/urban and coastal/inland environment on inflammatory bowel disease (IBD) are either conflicting or lacking. Our aim was to analyze whether the environment has any influence on the prevalence, phenotype, and course of IBD. Materials and methods We carried out a multicenter retrospective study in 1194 IBD patients from Galicia, Spain. Urban areas were defined as those with over 25 000 inhabitants. Sex, age, family history, smoking, Montreal classification, extraintestinal manifestations, steroid dependence/refractoriness, and treatment were assessed. We used the Student’s t-test/Mann–Whitney U tests to compare continuous variables and &khgr;2 to compare categorical variables. Logistic regression was also used. Results Living in urban municipalities was a risk factor for Crohn’s disease [relative risk (RR) 1.47; 95% confidence interval (CI) 1.25–1.73; P<0.001]; living in coastal municipalities was a protective factor for ulcerative colitis (RR 0.71; 95% CI 0.60–0.85; P<0.001). Crohn’s disease patients living on the coast had more frequent ileocolonic disease and needed immunosuppressives more frequently than inland patients (RR for inland 0.65; 95% CI 0.47–0.90; P=0.008). Urban Crohn’s disease patients needed immunosuppressives more frequently than rural patients (RR 1.41; 95% CI 1.04–1.92; P=0.027). Urban ulcerative colitis patients had left-sided colitis less frequently. Coastal ulcerative colitis patients more frequently had extensive colitis. Conclusion Crohn’s disease was found more frequently in urban and coastal areas and ulcerative colitis in inland municipalities. Place of residence may also influence phenotype and clinical course as patients living on the coast have more frequent ileocolonic Crohn’s disease phenotype, extensive ulcerative colitis, and greater need for immunosuppressive therapy.

Clinical practice in Crohn's disease in bordering regions of two countries: Different medical options, distinct surgical events

UNLABELLED Contemplating the multifactorial nature of Crohns disease (CD), the purpose of this study was to compare two neighbouring CD populations from different nations and examine how clinical characteristics of patients can influence therapeutic strategies and consequently different surgical events in routine clinical practice. Cross-sectional study based on data of an on-line registry of patients with CD in northern Portugal and Galicia. Of the 1238 patients, all with five or more years of disease, 568 (46%) were male and 670 (54%) female. The Portuguese and Galician populations were similar regarding Montreal categories, age at diagnosis, and years of follow-up. Galician B2 patients were associated with immunosuppression (OR 3.6; CI 2.2-6.1) and biologic treatment (OR 1.8; CI 1.0-3.1). In both populations ileocolonic disease was associated with immunosuppression and biologic treatment and the penetrating group was linked to immunosuppression. In the north of Portugal 47% and 16% of patients, and in Galicia 63% and 33%, were treated with immunosuppressants and biologic treatment, respectively. In the north of Portugal 44% of patients classified as stricturing behavior were operated without immunomodulation, in contrast to 12% in Galicia. In the latter it was possible to maintain 16% of B2 patients and 40% of B3 patients without surgery with adequate immunosuppression and/or biologic treatment. The delta of surgeries in B2 patients was 8% and in B3 26%. CONCLUSIONS Stratifying patients according to the Montreal classification identified similar clinical patterns in disparate geographic populations, and revealed that differing medical therapeutic practices may influence the occurrence of surgical events.

P152 Magnetic Resonance Enterography for the diagnosis and grading of postsurgical recurrence of Crohn's disease

Background: Two thirds of Crohn’s disease CD patients will require an intestinal resection. Postoperative recurrence is common. The severity of endoscopic recurrence is associated with early clinical recurrence and the need for reoperation. Postoperative endoscopic revision from 6 12 months after surgery has been protocolized with the purpose of detecting early recurrence and of introducing the best possible treatment. Methods: The aim was to compare Magnetic Resonance Enterography MRE and endoscopy in the detection of postsurgical recurrence. Thirty-six CD patients (females 21; mean age 41.2 years) with intestinal resection and ileocolic anastomosis underwent ileocolonoscopy and MRE. Diagnosis and grading was made according to the Rutgeerts score. MRE studies were performed at 1.0 T and evaluated by two radiologists with experience in abdominal radiology, blinded to endoscopy. A global assessment of disease activity at the anastomosis was performed using the MRE score for CD of our Hospital.

Pharmacogenetics Study of TMPT and ITPA Genes in Patients With Inflammatory Bowel Disease Treated With Azathioprine Detects Relation Between Itpase Deficiency and Clinical Response

Pharmacogenetics Study of TMPT and ITPA Genes in Patients With Inflammatory Bowel Disease Treated With Azathioprine Detects Relation Between Itpase Deficiency and Clinical Response Manuel Barreiro-de Acosta, William Zabala-Fernandez, Ana Echarri, Daniel Carpio, Aurelio Lorenzo, Javier A. Castro, Santos Pereira, David Martinez-Ares, Ignacio MartinGranizo, Marta Corton, Angel Carracedo, Francisco Barros

Can Early Anti-TNF Treatment Modify the Outcome of Inflammatory Strictures?

Background: Fatigue is a troubling problem for IBD patients and physicians alike. Recent population-based cohort studies by our group (Inflam Bowel Dis in press) and others have identified high levels of fatigue both when IBD is active (70-77%) and quiescent (30-36%). No previous studies have looked at fatigue over time in IBD. Methods: Data were obtained from Manitoba IBD Cohort Study participants (n=318; 51% Crohns disease CD), a longitudinal population based study of persons diagnosed within 7 years of enrolment. Disease activity was measured every 6 months for 2 years to characterize long-term disease pattern as active, fluctuating or inactive, using the validated Manitoba IBD Index (Am J Gastro 2009). Fatigue (Multidimensional Fatigue Inventory), psychological functioning, and blood markers were assessed concurrently at baseline and 1 and 2 years later. Results: 31% had consistently inactive, 28% had fluctuating, and 42% had consistently active disease across the two years. Fatigue levels mapped approximately to disease patterns, with lowest average fatigue at each time point for those with consistently inactive disease (see table). A mixedeffects regression model with a random intercept showed that fatigue levels increased over time regardless of disease pattern (F=8.38,p=0.004). There was substantial individual variation in fatigue levels at baseline (intraclass correlation ICC=0.44), with minimal individualspecific variation in the rate of change over time. A disease pattern x subtype interaction (p=0.01) suggested that UC participants with consistently inactive disease had modestly higher fatigue on average than those with inactive CD. Adjusting for disease activity and type, other factors were also found to be independently associated with fatigue across time including poor sleep quality (F= 16.04,p<0.001), higher stress (F=6.89, p=0.01), distress (F=32.34,p<0.001) and higher C-reactive protein levels (F=4.20,p=.04). Conclusion: Fatigue may worsen over time in IBD, even when disease is in remission. Changes in psychological factors are associated with changes in fatigue across time, suggesting that they may be a useful target for intervention in order to impact fatigue. Fatigue levels at baseline, year 1 & 2 for CD and UC across disease activity patterns

M1161 Extraintestinal Manifestations in Inflammatory Bowel Disease. Are They Associated with More Severe Disease

Background and Objectives: Corticosteroids (CS) are widely used effectively to induce remission in moderate to severe Crohns disease (CD). However, many patients do not respond (resistant) or require long-term treatment (dependent). CS responsiveness is an important concern in children as it is associated with increased surgical intervention and with susceptibility to side-effects. However, there is limited information on the natural history of CS responsiveness and clinical markers that could enable identification of children likely to respond to CS. We assessed the short and long term outcomes of the first course of CS therapy in children diagnosed with CD and investigated potential predictors of CS responsiveness. Methods: The study cohort comprised of children diagnosed with CD using standard criteria at a paediatric gastroenterology clinic in Montreal, Canada. All patients who received CS within 1 year of diagnosis were included. Clinical phenotypes were classified using the Montreal Classification. The medical files were reviewed retrospectively and sociodemographic and clinical information was abstracted. Recently reported CS response criteria were implemented to assess short and long term outcomes. The immediate response was assessed on 30th day of CS therapy. CS dependency was defined as a clinical relapse occurred during tapering or shortly after CS discontinuation. Chi square and Fishers exact tests and logistic regression were used to examine the relationship between CS response and variables such as age at diagnosis, gender and clinical phenotypes. Results: A total of 195 patients who were administered CS within 1 year since diagnosis, were identified. The majority of patients were males (113, 57.9%), had ileocolonic CD (L3±L4, 105, 53.8%) and mean age at diagnosis 12.3 (3.6). Of the 195 patients, 13 (6.66%) did not respond to CS, 109 (55.9%) and 73 (37.44%) achieved complete and partial response respectively. Among initial responders 72 (39.56%) became dependent later. Logistic regression analyses revealed that girls were more likely not to respond to CS therapy (OR=3.36; 95% CI, 0.99 to 1.31; p= 0.051). In comparison with patients who had prolonged response, CS dependent patients were more likely to be diagnosed with CD at a younger age (OR =0.85; 95% CI, 0.77 to 0.94, p=0.002). CS response was not associated with CD clinical phenotypes. Conclusion: Our findings highlight that whereas few children with CD are non-responsive to CS, a high proportion become CS dependent.Girls and children diagnosed at an earlier age appear to be more susceptible and alternatives to CS need to be considered in these patients.