Evaluation of the Risk of Relapse in Ulcerative Colitis According to the Degree of Mucosal Healing (Mayo 0 vs 1): A Longitudinal Cohort Study.

BACKGROUND AND AIMS: Mucosal healing in ulcerative colitis (UC) has become a common endpoint in most clinical trials and a relevant therapeutic goal in clinical practice. Despite important differences between endoscopic Mayo scores 0 and 1, both scores are considered as mucosal healing in most important trials. The aim of the present study was to evaluate the risk of relapse in UC patients according to the degree of mucosal healing (endoscopic Mayo scores of 0 and 1). METHODS: A prospective longitudinal cohort study was designed. All UC patients who presented with mucosal healing at colonoscopy were consecutively included. Mucosal healing was defined as an endoscopic Mayo score of 0 or 1. Clinical relapse was defined as the need for therapy to induce remission, any treatment escalation, hospitalization or colectomy. All clinical relapses were evaluated at months 6 and 12 after study entry. Results were subjected to unconditional stepwise logistic and Kaplan-Meier regression analysis. RESULTS: One hundred and eighty-seven consecutive UC patients (126 [67.3%] with Mayo score 0 and 61 [32.7%] with Mayo score 1) were included. Of patients with Mayo scores 0 and 1, 9.4 and 36.6% respectively presented a relapse during the first 6 months of follow-up (p < 0.001). The only factor independently associated with UC relapses in the multivariate analysis was an endoscopic Mayo score of 1 (odds ratio 6.27, 95% confidence interval 2.73-14.40, p < 0.001). CONCLUSIONS: Patients with an endoscopic Mayo score of 1 have a higher risk of relapse than those with a score of 0. The concept of mucosal healing should be limited to patients with an endoscopic Mayo score of 0.

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 χ 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, 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.

Efficacy of adalimumab for the treatment of extraintestinal manifestations of Crohn's disease.

BACKGROUND AND AIMS: Crohn's disease (CD) is commonly associated with inflammatory processes located in organs and systems others than the gut, which are known as extraintestinal manifestations (EIM) of the disease. The aim of this study was to assess the effectiveness of adalimumab (ADA) for the treatment of EIM in patients with CD. METHODS: forty two consecutive CD patients with at least one EIM were prospectively included in a open-label study. Patients received ADA (160 mg at week zero, 80 mg at week two and 40 mg every other week) over six months and the effectiveness and safety of ADA for EIMs were assessed. The influence of gender, age, smoking habits, family history of inflammatory bowel disease, phenotype and previous anti-TNF treatment on EIM resolution was also investigated. RESULTS: at month six, 76.2% of the patients showed remission or response in CD (33.3% remission and 42.9% any response). EIM showed a parallel course with CD in most cases, and showed remission or response in 66.7% of patients (38.1% remission and 28.5% any response). Patients with any response of their EIM condition were younger than those with no response (p = 0.04). No relationship was found between sex, tobacco, family history of IBD, phenotype and previous treatment with anti-TNF, and EIM resolution. CONCLUSIONS: adalimumab is effective in reducing EIM of CD. Age but not tobacco, CD phenotype and anti-TNF-naïve status appears to influence the response.

Efficacy of adalimumab for the treatment of extraintestinal manifestations of Crohn’s disease / Eficacia del adalimumab en el tratamiento de las manifestaciones extraintestinales de la enfermedad de Crohn

Background and aims: Crohn’s disease (CD) is commonly associated with inflammatory processes located in organs and systems others than the gut, which are known as extraintestinal manifestations (EIM) of the disease. The aim of this study was to assess the effectiveness of adalimumab (ADA) for the treatment of EIM in patients with CD. Methods: forty two consecutive CD patients with at least one EIM were prospectively included in a open-label study. Patients received ADA (160 mg at week zero, 80 mg at week two and 40 mg every other week) over six months and the effectiveness and safety of ADA for EIMs were assessed. The influence of gender, age, smoking habits, family history of inflammatory bowel disease, phenotype and previous anti-TNF treatment on EIM resolution was also investigated. Results: at month six, 76.2% of the patients showed remission or response in CD (33.3% remission and 42.9% any response). EIM showed a parallel course with CD in most cases, and showed remission or response in 66.7% of patients (38.1% remission and 28.5% any response). Patients with any response of their EIM condition were younger than those with no response (p = 0.04). No relationship was found between sex, tobacco, family history of IBD, phenotype and previous treatment with anti-TNF, and EIM resolution. Conclusions: adalimumab is effective in reducing EIM of CD. Age but not tobacco, CD phenotype and anti-TNF-naïve status appears to influence the response(AU)

Complementary and alternative medicine in inflammatory bowel disease patients: frequency and risk factors.

BACKGROUND: The use of complementary and alternative medicine in inflammatory bowel disease patients is progressively increased. AIM: To evaluate the use of complementary and alternative medicine in inflammatory bowel disease patients and to know potential risk factors for their use. The subjective response of these therapies and the impact on treatment adherence were also evaluated. METHODS: Prospective, descriptive and transversal study. Inflammatory bowel disease patients were classified according to demographic and clinical characteristics. A questionnaire about the use of complementary and alternative medicine was collected. RESULTS: 705 patients were included. 126 patients (23%) had used complementary and alternative medicine. The most commonly used was herbal remedies (n=61), homoeopathy (n=36), acupuncture (n=31), kefir (n=31) and aloe vera (n=25). Factors associated with its use were extraintestinal manifestations (OR 1.69, CI 95% 1.11-2.57) and long-term evolution of the disease (OR 2.08, CI 95% 1.44-2.99). Most patients (74%) had the subjective feeling that use of complementary and alternative medicine had not improved their condition, 11 had adverse events related to its use and 11% of patients discontinued their conventional drugs. CONCLUSIONS: Use of complementary and alternative medicine in inflammatory bowel disease patients is frequent, especially in those with extraintestinal manifestations and long-term evolution. The use of these therapies was not perceived as a benefit for patients.

A pharmacogenetics study of TPMT and ITPA genes detects a relationship with side effects and clinical response in patients with inflammatory bowel disease receiving Azathioprine.

BACKGROUND AND AIMS: Pharmacogenetic studies in inflammatory bowel diseases (IBD) are mainly focused on genes involved in the metabolism of Azathioprine (AZA). Use of AZA is limited by its toxicity, which occurs in 20-30% of patients. Variants in the Thiopurine S-methyltransferase (TPMT) and Inosine triphosphate pyrophosphatase (ITPA) genes have been associated with AZA toxicity, but also can contribute to the lack of response. The aims of this study were to determine the contribution of TPMT and ITPA variants in the development of AZA-related toxicity and response. METHODS: Variants associated with the decrease of enzyme activity in TPMT and ITPA genes were genotyped with the Snapshot system in 232 IBD patients treated with AZA, and correlated with the clinical response and development of adverse drug reactions in a retrospective case-control study. RESULTS: Genotypic analysis showed that there is a statistical significance between c.94C > A variant on ITPA gene with non response to AZA treatment (p=0.005) and arthralgia (OR 8.2353; 95%CI 1.752-38.87, p=0.0041), as well as between mutant TPMT alleles and myelosuppression (OR 7.5; 95%CI 1.4456-38.91, p=0.0304). CONCLUSIONS: There is a positive correlation between c.94C > A variant on ITPA with clinical response. Mutant alleles on TPMT and the variant c.94C > A on ITPA gene predict side effects induced by AZA in our population (myelosuppression and arthralgia).

Efficacy of intravenous iron in treating iron deficiency anaemia in patients with inflammatory bowel disease. Are there predictors of response?

INTRODUCTION: In inflammatory bowel disease (IBD) iron deficiency anaemia (IDA) is a very common disorder. Until recently,oral iron has been the mainstay therapy, nevertheless it has been associated with intolerance and noncompliance. Therefore, the goal of our study was to evaluate the efficacy of intravenous iron in IDA in IBD patients and the secondary aim was to investigate whether other potencial factors could influence in the response to the treatment. DESIGN: An open-label, prospective, consecutive, single centre study. MATERIAL AND METHODS: We performed our study in patients with ulcerative colitis (UC) or Crohn´s disease (CD) with severe anaemia or intolerance with oral iron. All of them received intravenous sacarose iron and did biochemistry profile with hemoglobin (Hb). Moreover, the correlation with other variables was studied: age,sex, smoking habit, IBD type, previous surgery and type of surgery and other treatments. Response was defined as Hb increase of ≥ 2 g/dL or normalization of the levels. RESULTS: Fifty-four patients were included into the study, 34(63%) with UC y 20 (37%) with CD, 18 (33.3%) men and 36 wo-men (66.6%) and the average was 48 +/- 14 years. The total proportion of responders was 52% (SD +/- 05); 43% of the patients reached Hb ≥ 2 g/dl and y 9% of them normalized Hb. Only the utilization of 5-ASA was associated with low response to iron treatment (p < 0.05). CONCLUSIONS: Our study suggests that response to intravenous iron is achievable in the majority of patients with IBD and severe IDA or intolerance treatment with oral iron. Moreover, the patients with consumption of 5-ASA could had less response to the treatment.

Eficacia del hierro intravenoso en el tratamiento de la anemia ferropénica en pacientes con enfermedad inflamatoria intestinal. ¿Existen factores predictivos de respuesta? / Efficacy of intravenous iron in treating iron deficiency anaemia in patients with inflammatory bowel disease. Are there predictors of response?

Introducción: la anemia por déficit de hierro es un problema frecuente en la enfermedad inflamatoria intestinal (EII). Un número no despreciable de pacientes no responde o presenta intolerancia al hierro oral. El objetivo de nuestro estudio es evaluar la efica - cia del hierro sacarosa intravenoso (Venofer®) en los pacientes con EII así como los potenciales factores que pueden influir en la respuesta al mismo. Diseño: estudio abierto, unicéntrico y con una inclusión consecutiva de casos. Material y métodos: se incluyeron pacientes con colitis ulcerosa (CU) y enfermedad de Crohn (EC) con anemia grave o anemia moderada con intolerancia al hierro oral. A todos los pacientes se les administró hierro sacarosa intravenoso y se les realizó una analítica que incluía hemoglobina (Hb). Además fueron estratificados según edad, sexo, hábito tabáquico, localización, patrón de la enfermedad, cirugías previas, tipos de cirugías, otras manifestaciones extraintestinales y tratamientos concomitantes. Se consideró como respuesta al tratamiento un aumento de la Hb igual o mayor de 2 g/dl o la normalización de la misma. Resultados: se incluyeron 54 pacientes, 34 (63%) con CU y 20 (37%) con EC, 18 (33,3%) hombres y 36 mujeres (66,6%), con edad media de 48 ± 14 años. El porcentaje total de respondedores se situó en el 52% (DE ± 0,5); un 43% experimentó un incremento de la Hb >= 2 g/dl y un 9% normalizó las cifras de Hb. En cuanto a los demás factores analizados tan solo se observó una disminución de respuesta al tratamiento en los pacientes que recibieron5-ASA (p < 0,05). Conclusiones: el tratamiento con hierro sacarosa intravenoso podría ser eficaz en los pacientes con EII con anemia grave o intolerancia al hierro oral. La utilización de salicilatos podría influir en la respuesta al tratamiento(AU)

Introduction: in inflammatory bowel disease (IBD) iron deficiency anaemia (IDA) is a very common disorder. Until recently, oral iron has been the mainstay therapy, nevertheless it has been associated with intolerance and noncompliance. Therefore, the goal of our study was to evaluate the efficacy of intravenous iron in IDA in IBD patients and the secondary aim was to investigate whether other potencial factors could influence in the response to the treatment. Design: an open-label, prospective, consecutive, single centre study. Material and methods: we performed our study in patients with ulcerative colitis (UC) or Crohn’s disease (CD) with severe anaemia or intolerance with oral iron. All of them received intravenous sacarose iron and did biochemistry profile with hemoglobine (Hb). Moreover, the correlation with other variables was studied: age, sex, smoking habit, IBD type, previous surgery and type of surgery and other treatments. Response was defined as Hb increase of >= 2 g/dL or normalization of the levels. Results: fifty-four patients were included into the study, 34 (63%) with UC y 20 (37%) with CD, 18 (33.3%) men and 36 women (66.6%) and the average was 48 ± 14 years. The total proportion of responders was 52% (SD ± 05); 43% of the patients reached Hb >= 2 g/dl and y 9% of them normalized Hb. Only the utilization of 5-ASA was associated with low response to iron treatment (p < 0.05). Conclusions: our study suggests that response to intravenous iron is achievable in the majority of patients with IBD and severe IDA or intolerance treatment with oral iron. Moreover, the patients with consumption of 5-ASA could had less response to the treatment(AU)

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

UNLABELLED: Contemplating the multifactorial nature of Crohn's 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.

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

BACKGROUND: Infliximab has improved the management of perianal Crohn's 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 Crohn's 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.

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.

Adalimumab in ulcerative colitis: two cases of mucosal healing and clinical response at two years.

Infliximab (IFX) is currently the only biologic therapy used in the treatment of moderate-to-severe ulcerative colitis (UC). In the years to come, more biologic therapies will have a role in the management of moderate-to-severe UC. We report on two patients with steroid-dependent UC who, due to adverse reactions to IFX, have been under therapy with adalimumab for two years. Both patients received concomitant immunosuppressive treatment. Long term clinical remission and mucosal healing are described.

Mucosal healing and steroid-sparing associated with infliximab for steroid-dependent ulcerative colitis.

BACKGROUND: Corticosteroid therapy for ulcerative colitis (UC) frequently results in Steroid-dependency. The objective of this study was to evaluate the long term clinical and endoscopic efficacy of infliximab (IFX) in steroid-dependent UC. METHODS: An open-label, prospective, single center study was designed. Patients older than 18 years with steroid-dependent UC, either intolerant or did not respond to azathioprine, were consecutively enrolled. Steroid-dependency was defined as the ECCO criteria. Patients received IFX (5 mg/kg) at 0, 2 and 6 weeks and every 8 weeks thereafter for 2 years. All patients were clinically evaluated at weeks 8, 52 and 104 and a colonoscopy was performed at week 104. Response to IFX was defined as clinical remission without steroids together with mucosal healing (endoscopic Mayo score of 0 or 1). RESULTS: Seventeen consecutive patients were included (11 male, mean age 45, range 25-70). Thirteen (76%) had extensive colitis (E3). All patients completed IFX therapy. Clinical response was in 13/17 at weeks 8 and 52. Twelve out of seventeen patients maintained clinical remission without steroids and endoscopic response at week 104. Six out of seventeen patients needed dose intensification of IFX (every 6 weeks); 3/6 patients did not reach remission despite dose intensification. Including those patients who needed dose intensification as non-responders, 9/17 patients were in clinical and endoscopic remission at week 104. A significant correlation was found between clinical and endoscopic findings (p<0.01). CONCLUSIONS: Infliximab therapy is effective for maintenance of clinical remission and mucosal healing in patients with steroid-dependent UC.

Relationship between clinical features of Crohn's disease and the risk of developing extraintestinal manifestations.

OBJECTIVES: Crohn's disease is frequently associated with extraintestinal manifestations. The aim of this study was to evaluate the degree of association between the development of extraintestinal manifestations, the clinical forms of Crohn's disease according to the Vienna Classification and to the presence of several potential risk factors of the disease. METHODS: One hundred and seventy-three consecutive Crohn's disease patients were studied. Sex, smoking habits, previous Crohn's disease-related surgery, family history of Crohn's disease, steroid dependency, steroid resistance and the presence of at least one mutant allele in any of the three considered variants of CARD15 gene were considered as potential risk factors. The Vienna Classification was applied, and the presence of extraintestinal manifestations was evaluated. RESULTS: A total of 61 (35.3%) patients developed extraintestinal manifestations. They were more frequently seen in women than in men (41.1 vs. 26.7%), (odds ratio 1.92, 95% confidence interval: 0.99-3.70; P=0.05) and in steroid-dependent patients than in steroid responders (61.1 vs. 28.5%), (odds ratio 3.94, 95% confidence interval: 1.83-8.49; P<0.01). No relationship was found in general between the extraintestinal manifestations of Crohn's disease and smoking habits, previous Crohn's disease-related surgery, a family history of Crohn's disease, steroid resistance and CARD15 mutations. Such relationships were, however, detected for some individual extraintestinal manifestations as between both smoking habits (odds ratio 9.09, 95% confidence interval: 1.15-71.66; P<0.05) and the G908R CARD15 mutation (odds ratio 4.76, 95% confidence interval: 1.11-20.43; P<0.05), respectively, and erythema nodosum. Patients with any colonic involvement of Crohn's disease (L2+L3) suffered from extraintestinal manifestations of the disease more frequently than patients without colonic involvement (42.7 vs. 25.9%, respectively; odds ratio 2.12, 95% confidence interval: 1.10-4.07; P<0.05). CONCLUSIONS: Female gender, steroid-dependency and colonic involvement are associated with the risk of developing extraintestinal manifestations of Crohn's disease.

CARD15 mutations in patients with Crohn's disease in a homogeneous Spanish population.

OBJECTIVES: Three mutations in CARD15 have been repeatedly shown to be involved in Crohn's disease susceptibility, mainly in Caucasian individuals. However, those findings were not replicated in all populations studied so far. In this work, we studied the role of CARD15 mutations in a relatively homogeneous population from the Northwest of Spain, Galicia. METHODS: One hundred and sixty-five patients with Crohn's disease and a similar number of healthy controls were recruited from a single center in Galicia. All individuals were genotyped for the three main Crohn's disease associated CARD15 variants (R702W, G908R, and 1007fs). Association analyses were performed to study the influence of those mutations on Crohn's disease overall and on clinical subphenotypes. RESULTS: The allele frequencies of CARD15 variants were lower in this population than in most of the European populations studied so far. G908R and 1007fs were significantly associated with overall susceptibility to Crohn's disease. However, these associations were lost after stratification to clinical subgroups, probably due to the small number of cases in these subgroups. Significant associations were found between G908R and 1007fs and the behavior of Crohn's disease, but they were due to the influence of years of disease on the behavior of the disease rather than being the result of a direct effect of these mutations on disease behavior. CONCLUSIONS: The CARD15 variants G908R and 1007fs, but not R702W, are associated with susceptibility to Crohn's disease in Galicia. Interestingly, the frequency of these mutations appears to be lower than in other Caucasian populations studied so far.