Efficacy of beclomethasone dipropionate in lowering fecal calprotectin levels in patients with ulcerative colitis in clinical remission and at risk of relapse: The Becalcu randomized, controlled trial.

INTRODUCTION: Identifying novel treatment strategies for patients with ulcerative colitis (UC) and at risk of relapse is critical. The objective of this study was to assess the efficacy of beclomethasone dipropionate (BDP) in lowering fecal calprotectin (FC) levels in UC patients in clinical remission and at risk of relapse. METHODS: This multicenter study comprised a double-blind, randomized, placebo-controlled phase (part I) and an open-label, non-randomized phase (part II). Eligible participants with UC in clinical remission, treated with 5-aminosalicylic acid and with FC levels ≥250 µg/g were randomized to receive 5 mg/day of BDP or placebo for 4 weeks (part I). At week 5, patients with FC ≥100 µg/g were treated with 5 mg/day of BDP for 4 weeks (part II), and FC levels were tested at week 9. RESULTS: Forty-three patients were randomized: 22 received BDP (group A) and 21 placebo (group B). At week 4, 13 patients (59.1%) in group A and 3 (17.6%) in group B had FC levels <100 µg/g (p-value = 0.010). In the double-blind phase of the study, no patient relapsed in group A and 4 in group B (p-value = 0.049). Both treatment groups showed a favorable safety profile, with most common adverse events being gastrointestinal disorders. CONCLUSION: In this multicenter, randomized clinical trial including patients with UC in clinical remission but with elevated FC, BDP was efficacious in reducing FC and well-tolerated.

Encuesta Sociedad Española de Médicos de Atención Primaria (SEMERGEN) y Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el manejo de pacientes con enfermedad inflamatoria intestinal / Spanish Society of Primary Care Physicians (SEMERGEN) and Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) survey on the management of patients with inflammatory bowel disease

Introducción: La colaboración entre Atención Primaria (AP) y Gastroenterología en la enfermedad inflamatoria intestinal (EII) es crucial para ofrecer una atención médica de alta calidad. El objetivo del presente estudio es analizar, en el ámbito nacional, la relación entre AP y los gastroenterólogos con el objetivo de conocer los aspectos de mejora en el manejo de pacientes con EII y cómo poder implementarlos, para así desarrollar posteriormente propuestas y proyectos concretos entre SEMERGEN y GETECCU. Metodología: Estudio descriptivo, observacional y transversal, realizado mediante cuestionario online anónimo entre octubre de 2021 y marzo de 2022. Resultados: Se recopilaron un total de 157 encuestas de Gastroenterología y 222 de AP. El 43,8% y el 34,3% de los gastroenterólogos y médicos de familia, respectivamente, consideraron tener una buena relación. El grado de conocimiento de los médicos de familia sobre diferentes aspectos de la EII (puntuado sobre 10) fue: aspectos clínicos 6,67±1,48, diagnósticos 6,47±1,46, terapéuticos 5,63±1,51, de seguimiento 5,53±1,68 y complicaciones 6,05±1,54. La percepción del apoyo y soporte entre ambas unidades no superó el 4,5 en una escala de 0 a 10 en ninguna de las encuestas. Las propuestas de mejora más votadas fueron: mayor coordinación entre especialistas, implantación de unidades de EII y colaboración de enfermería. Conclusión: Existen deficiencias en la relación entre AP y Gastroenterología con especial dedicación a la EII que requiere de los esfuerzos de las sociedades científicas que los representan para una mayor coordinación, con elaboración de protocolos conjuntos y medios de comunicación ágiles, rápidos y efectivos. (AU)

Introduction: Collaboration between Primary Care (PC) and Gastroenterology in inflammatory bowel disease (IBD) is crucial to provide high-quality healthcare. The aim of this study is to analyse the relationship between PC and gastroenterologists at a national level in order to identify areas for improvement in the management of patients with inflammatory bowel disease (IBD) and how to address them, with the aim of subsequently developing concrete proposals and projects between SEMERGEN and GETECCU. Methods: Descriptive, observational, cross-sectional study, was carried out using an anonymous online questionnaire between October 2021 and March 2022. Results: A total of 157 surveys from Gastroenterology and 222 from PC were collected. 43.8% and 34.3% of gastroenterologists and family practitioners, respectively, considered that there was a good relationship between the units. The level of knowledge from family practitioners regarding different aspects of IBD out of 10 was: clinical 6.67±1.48, diagnosis 6.47±1.46, treatment 5.63±1.51, follow-up 5.53±1.68 and complications 6.05±1.54. The perception of support between both units did not exceed 4.5 on a scale from 0 to 10 in either of the surveys. The most highly voted improvement proposals were better coordination between the units, implementation of IBD units, and nursing collaboration. Conclusion: There are deficiencies in the relationship between PC and Gastroenterology with special dedication to IBD that require the efforts of the scientific societies that represent them for greater coordination with the development of joint protocols and agile, fast, and effective communication channels. (AU)

Spanish Society of Primary Care Physicians (SEMERGEN) and Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) survey on the management of patients with inflammatory bowel disease. / Encuesta Sociedad Española de Médicos de Atención Primaria (SEMERGEN) y Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el manejo de pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Collaboration between Primary Care (PC) and Gastroenterology in inflammatory bowel disease (IBD) is crucial to provide high-quality healthcare. The aim of this study is to analyse the relationship between PC and gastroenterologists at a national level in order to identify areas for improvement in the management of patients with inflammatory bowel disease (IBD) and how to address them, with the aim of subsequently developing concrete proposals and projects between SEMERGEN and GETECCU. METHODS: Descriptive, observational, cross-sectional study, was carried out using an anonymous online questionnaire between October 2021 and March 2022. RESULTS: A total of 157 surveys from Gastroenterology and 222 from PC were collected. 43.8% and 34.3% of gastroenterologists and family practitioners, respectively, considered that there was a good relationship between the units. The level of knowledge from family practitioners regarding different aspects of IBD out of 10 was: clinical 6.67±1.48, diagnosis 6.47±1.46, treatment 5.63±1.51, follow-up 5.53±1.68 and complications 6.05±1.54. The perception of support between both units did not exceed 4.5 on a scale from 0 to 10 in either of the surveys. The most highly voted improvement proposals were better coordination between the units, implementation of IBD units, and nursing collaboration. CONCLUSION: There are deficiencies in the relationship between PC and Gastroenterology with special dedication to IBD that require the efforts of the scientific societies that represent them for greater coordination with the development of joint protocols and agile, fast, and effective communication channels.

Relevancia y necesidades del síndrome del intestino irritable (SII): comparación con la enfermedad inflamatoria intestinal (EII). (Por favor, si no te interesa el SII, léelo.) / Relevance and needs of irritable bowel syndrome (IBS): Comparison with inflammatory bowel disease (IBD). (Please, if you are not interested in IBS, read it.)

Introducción: En nuestra opinión existe un desequilibrio entre la relevancia del síndrome del intestino irritable (SII) y los medios que se le proporcionan. Objetivo: Revisar los diferentes factores que determinan (o deberían determinar) el interés de los gastroenterólogos por el SII, comparándolo con la enfermedad inflamatoria intestinal (EII). Para ello se han analizado 7 áreas diferentes: 1.Impacto médico; 2.Impacto social; 3.Importancia académica; 4.Relevancia clínica; 5.Relevancia científica; 6.Relevancia pública, y 7.Aspectos personales del médico. Resultados: La prevalencia es 10 veces superior en el SII, suponiendo hasta el 25% de las visitas del gastroenterólogo. Ambas patologías alteran la calidad de vida, en muchos casos de forma semejante. El coste social es muy importante en ambos casos (p.ej., absentismo del 21 y del 18%), así como el económico, aunque muy superior en medicación para la EII. La dedicación académica es más del doble para la EII, tanto en la universidad como en la formación MIR. La relevancia científica es mayor en la EII, con un número de publicaciones cuatro veces superior. La relevancia pública no es muy diferente entre las dos entidades, aunque los pacientes con EII son más asociativos. Los médicos prefieren la EII y tienden a estigmatizar el SII. Conclusión: En nuestra opinión, para disminuir este desequilibrio entre necesidades y recursos, humanos y materiales, en el SII es imprescindible realizar cambios drásticos tanto en los aspectos educativos, de habilidades de comunicación, de priorización de acuerdo con las demandas de los pacientes, y de recompensa (personal y social) de los médicos.(AU)

Introduction: In our opinion there is an imbalance between the relevance of irritable bowel syndrome (IBS), and the resources that are provided. Objective: To review the different factors that determine (or should determine) the interest of gastroenterologists in IBS, comparing it with inflammatory bowel disease (IBD). For this, 7 different areas have been analyzed: (1)Medical impact; (2)Social impact; (3)Academic importance; (4)Clinical relevance; (5)Scientific relevance; (6)Public relevance, and (7)Personal aspects of the doctor. Results: The prevalence is 10 times higher in IBS, which represents up to 25% of gastroenterologist visits. Both pathologies alter the quality of life, in many cases in a similar way. The social cost is very important in both cases (e.g.: absenteeism of 21% and 18%) as well as the economic cost, although much higher in medication for IBD. Academic dedication is more than double for IBD, both in university and in MIR training. Scientific relevance is greater in IBD, with a number of publications four times higher. Public relevance is not very different between the two entities, although IBD patients are more associative. Doctors prefer IBD and tend to stigmatize IBS. Conclusion: In our opinion, to reduce this imbalance between needs and resources, human and material, in IBS it is essential to make drastic changes both in educational aspects, communication skills, prioritization according to the demands of patients, and reward (personal and social) of physicians.(AU)

LIAISON® Calprotectin for the prediction of relapse in quiescent ulcerative colitis: The EuReCa study.

INTRODUCTION: Fecal calprotectin (FC) is established as a diagnostic marker to differentiate between inflammatory bowel diseases and non-inflammatory conditions. Furthermore, it may be effective in monitoring response to treatment, and to predict relapse during maintenance therapy. DESIGN: This was a prospective longitudinal study carried out in Italy, France and Spain. The primary objective was to correlate the LIAISON® Calprotectin assay measurements to quiescent ulcerative colitis (UC) or relapse as assessed by clinical data. Patients were assessed every 3 months for 12 months, and at 18 months. RESULTS: The last FC measured prior to relapse was the variable that predicted relapse in a statistically significant manner. With a 62.3 µg/g cut-off the area under the curve was 0.619, and the sensitivity was 62.9% (95% Confidence Interval [CI] 44.9%-78.5%) and specificity 63.0% (95% CI 53.1%-72.1%). Using machine learning methods, the last FC measurement was shown to have the largest impact in predicting relapse. An algorithm was developed that included other variables available following a clinician's visit, which resulted in an area under the curve of 0.754 for predicting relapse. CONCLUSION: In the present study FC measured by the LIAISON® Calprotectin assay on the visit before relapse is predictive of relapse in patients with quiescent UC. In a proof of concept, the accuracy of prediction can further be improved including other variables in an algorithm developed by machine learning. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov with reference number NCT05168917.

Relevance and needs of irritable bowel syndrome (IBS): Comparison with inflammatory bowel disease (IBD). (Please, if you are not interested in IBS, read it.). / Relevancia y necesidades del síndrome del intestino irritable (SII): comparación con la enfermedad inflamatoria intestinal (EII). (Por favor, si no te interesa el SII, léelo.).

INTRODUCTION: In our opinion there is an imbalance between the relevance of irritable bowel syndrome (IBS), and the resources that are provided. OBJECTIVE: To review the different factors that determine (or should determine) the interest of gastroenterologists in IBS, comparing it with inflammatory bowel disease (IBD). For this, 7 different areas have been analyzed: (1)Medical impact; (2)Social impact; (3)Academic importance; (4)Clinical relevance; (5)Scientific relevance; (6)Public relevance, and (7)Personal aspects of the doctor. RESULTS: The prevalence is 10 times higher in IBS, which represents up to 25% of gastroenterologist visits. Both pathologies alter the quality of life, in many cases in a similar way. The social cost is very important in both cases (e.g.: absenteeism of 21% and 18%) as well as the economic cost, although much higher in medication for IBD. Academic dedication is more than double for IBD, both in university and in MIR training. Scientific relevance is greater in IBD, with a number of publications four times higher. Public relevance is not very different between the two entities, although IBD patients are more associative. Doctors prefer IBD and tend to stigmatize IBS. CONCLUSION: In our opinion, to reduce this imbalance between needs and resources, human and material, in IBS it is essential to make drastic changes both in educational aspects, communication skills, prioritization according to the demands of patients, and reward (personal and social) of physicians.

International Perspectives on Management of Inflammatory Bowel Disease: Opinion Differences and Similarities Between Patients and Physicians From the IBD GAPPS Survey.

BACKGROUND: Inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), are complex disorders with multiple comorbidities. We conducted international patient and physician surveys to evaluate current experiences and perceptions of patients with CD or UC and physicians who treat IBD. METHODS: The IBD Global Assessment of Patient and Physician Unmet Need Surveys comprised a patient survey and a physician survey, fielded in North America and Europe between August 16, 2019, and November 10, 2019. Adults with CD or UC (targeted 1:1 ratio) were recruited from physicians, patient advocacy groups, and recruitment panels; physicians were recruited by recruitment agencies and panels. RESULTS: In total, 2398 patients with IBD (1368 CD, 1030 UC) and 654 physicians completed surveys. Anxiety and depression were the most common comorbidities among patients with IBD. Patients and physicians were generally aligned on treatment goals and patient-physician communication. Patients with IBD reported high quality-of-life impact by rectal urgency and need to use the toilet, which were rated as lower-impact by physicians. Patients defined remission based on symptoms; physicians defined remission based primarily on clinical tests. Patients expected current treatments to control their disease for a longer duration than did physicians. Patients expressed more concern about corticosteroid use compared with physicians; many physicians reported prescribing corticosteroids for more than 4 months per year in some patients. CONCLUSIONS: Patients could benefit from education about disease remission and expectations for current therapies. High corticosteroid use is concerning to patients, and physicians should minimize the use of corticosteroids for extended periods of time.

3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 1: Diagnosis and Medical Management.

This paper is the first in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the methodology of the consensus process, and the classification, diagnosis and medical management of active and quiescent Crohn's disease. Surgical management as well as special situations including management of perianal Crohn's disease of this ECCO Consensus are covered in a subsequent second paper [Gionchetti et al JCC 2016].

Long-Term Follow-Up of Patients Treated with Infliximab for Ulcerative Colitis: Predictive Factors of Response-An Observational Study.

AIM: To evaluate the early and long-term efficacy of infliximab in ulcerative colitis and to determine predictors of response and colectomy. METHODS: This is an ambidirectional cohort study in a tertiary referral center including patients who started infliximab within 2005 and 2008 and monitored until 2014. Efficacy was evaluated by partial Mayo scores at weeks 2, 4, 8, 30, and 54. Long-term treatment maintenance with infliximab and colectomy requirements were recorded. RESULTS: Fifty-three patients were included with a median follow-up of 69.5 months. Clinical remission at the time point assessments was 40.8, 47.2, 54.7, 54.7, and 49.1 %. At the time of maximal follow-up, the proportion of patients under infliximab maintenance was 24.5 %. A higher level of albumin (OR 1.4, CI 95 % 1.06-1.8; p = 0.017) was predictive of a higher remission rate at week 8. Concomitant immunomodulators beyond 6 months were predictive of infliximab's long-term maintenance (OR 15.8, CI 95 % 1.8-135.4; p = 0.012). Colectomy was required in 41.5 %. Factors associated with a higher rate of colectomy at week 54 were previous treatment with cyclosporine (OR 3.4, CI 95 % 1.2-9.7; p = 0.012), absence of response at week 8 (OR 10.3, CI 95 % 3.3-31.7; p < 0.001), and not receiving concomitant immunomodulators (OR 4.1, CI 95 % 1.8-9; p = 0.002). Colectomy rates within the first 54 weeks were closely dependent on the number of variables present: none (0 %), 1 (26.3 %), 2 (71.4 %), or 3 (100 %) of them (log rank <0.0001). CONCLUSIONS: Low albumin, previous treatment with cyclosporine, absence of a concomitant immunomodulator, and lack of response at week 8 negatively affected the efficacy of infliximab in ulcerative colitis.

Impact of Smoking Cessation on the Clinical Course of Crohn's Disease Under Current Therapeutic Algorithms: A Multicenter Prospective Study.

OBJECTIVES: Given the importance of tobacco smoking (TS) as the only environmental factor repeatedly linked to the development of the Crohn's disease (CD), it is surprising that very few prospective studies have assessed whether TS is associated with an increased frequency of clinical relapse. Our aim was to evaluate the current impact of TS on disease relapse and the clinical benefit of quitting smoking in the present era of widespread use of anti-TNF drugs and immunosuppressants. METHODS: This was a multicenter prospective cohort study, which included 573 CD patients in clinical remission with various smoking habits. All smokers were advised to quit. Patients not exposed to tobacco before inclusion (non- and former smokers), continuing smokers, and quitters were compared regarding differences in disease outcomes during a follow-up of 4 years. RESULTS: A total of 148 continuing smokers, 190 nonsmokers, 160 former smokers, and 75 quitters were included. In comparison with nonsmokers, continuing smokers relapsed more frequently with an incidence rate ratio of 1.53 (95% confidence interval (CI): 1.10-2.17). Former smokers and quitters had similar relapse incidences compared with nonsmokers. Smoking was an independent predictor for disease relapse in the multivariate analysis (hazard ratio: 1.58 (95% CI 1.20-2.09). In the time-dependent analysis, continuing smokers had earlier relapse, regardless of anti-TNF or immunosuppressant use. CONCLUSIONS: Continuing smokers have more disease relapses, and patients who quit smoking have a similar relapse incidence compared with nonsmokers.

Accuracy of advanced endoscopy and fecal calprotectin for prediction of relapse in ulcerative colitis: a prospective study.

BACKGROUND: The aim of this study was to determine the accuracy of advanced endoscopy for prediction of relapse in ulcerative colitis, in comparison with serum and fecal biomarkers. METHODS: Patients with ulcerative colitis with sustained clinical remission defined as absence of blood in stool for a minimum of 3 months and Mayo endoscopic subscore of 0 were included. High-resolution rectosigmoidoscopy was performed at baseline and at the end of study (week 52 or relapse), assessing mucosal pit pattern by chromoendoscopy and narrow band imaging as well as vascular pattern by narrow band imaging. Histology was evaluated at baseline and at the end of the study. Follow-up for 1 year or until relapse with clinical evaluations and serum and fecal biomarkers every 3 months was established. Relapse was defined as presence of blood in stool and a Mayo endoscopic subscore ≥1 with histologic confirmation. RESULTS: Seventeen out of 64 patients (27%) relapsed during the follow-up period. Baseline clinical characteristics in patients who relapsed and those who did not were similar. Neither pit or vascular pattern nor histology was significantly different between relapsers and nonrelapsers. Among serum biomarkers, high platelet count was significantly associated with higher relapse rates. Fecal calprotectin was predictor of relapse within 3- and 12-month period with high specificity but low sensitivity. CONCLUSIONS: Advanced endoscopy and histology do not predict relapse over 1-year period in patients with ulcerative colitis. Fecal calprotectin can predict relapse in 3- and 12-month period with low accuracy.

Pancreatitis-associated protein does not predict disease relapse in inflammatory bowel disease patients.

BACKGROUND: The pancreatitis-associated protein (PAP) is increased in the serum of active inflammatory bowel disease (IBD) patients and its levels seem to be correlated with disease activity. Our aim was to evaluate the usefulness of serum and fecal PAP measurements to predict relapse in patients with inactive IBD. MATERIALS AND METHODS: We undertook a 12-month prospective study that included 66 Crohn's disease (CD) and 74 ulcerative colitis (UC) patients. At inclusion, patients were in clinical remission, defined by a Harvey-Bradshaw (HB) Index≤4 (CD) or a partial Mayo Score (MS)<3 (UC), along with a normal serum C reactive protein (CRP) and fecal calprotectin. Patients were followed every 3 months. Blood and stool samples were collected and a clinical evaluation was performed at each visit. Serum PAP and CRP levels as well as fecal concentrations of PAP and calprotectin were assessed. RESULTS: Active CD patients had an increased mean serum PAP at the diagnosis of the flare (104.1 ng/ml) and 3 months prior to activity (22.68 ng/ml) compared with patients in remission (13.26 ng/ml), p<0.05. No significant change in serum PAP levels in UC and fecal PAP levels in CD and UC were detected during disease activity. In CD, serum PAP was a poor diagnostic predictor of disease activity, with an AUC of 0.69. In patients in remission, fecal PAP was barely detectable in UC compared with CD patients. CONCLUSION: Serum PAP is increased only in active CD patients, but this marker does not predict disease activity. Inactive UC patients have marked low levels of PAP in fecal samples compared with CD patients.

Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn's disease.

BACKGROUND & AIMS: A small placebo-controlled trial reported the efficacy of mercaptopurine therapy for children newly diagnosed with Crohn's disease, yet little is known about the efficacy of early thiopurine therapy in adults. METHODS: We performed a prospective double-blind trial of adult patients with a recent (<8 weeks) diagnosis of Crohn's disease. Patients were randomly assigned to groups given azathioprine (2.5 mg · kg(-1) · day(-1), n = 68) or placebo (n = 63) at 31 hospitals from February 2006 to September 2009. Corticosteroids but no other concomitant medications were allowed for control of disease activity. The primary measure of efficacy was sustained corticosteroid-free remission. RESULTS: After 76 weeks of treatment, 30 patients treated with azathioprine (44.1%) and 23 given placebo (36.5%) were in sustained corticosteroid-free remission (difference of 7.6%; 95% confidence interval, -9.2 to 24.4%; P = .48). The rates of relapse (defined as Crohn's Disease Activity Index score >175) and corticosteroid requirements were similar between groups. A post hoc analysis of relapse, defined as a Crohn's Disease Activity Index score >220, showed lower relapse rates in the azathioprine group than in the placebo group (11.8% vs 30.2%; P = .01). Serious adverse events occurred in 14 patients in the azathioprine group (20.6%) and 7 in the placebo group (11.1%) (P = .16). A larger percentage of patients in the azathioprine group had adverse events that led to study drug discontinuation (20.6%) than in the placebo group (6.35%) (P = .02). CONCLUSIONS: In a study of adults with Crohn's disease, early azathioprine therapy was no more effective than placebo to achieve sustained corticosteroid-free remission but was more effective in preventing moderate to severe relapse in a post hoc analysis. EudraCT 2005-001186-34.

Association between variants of PRDM1 and NDP52 and Crohn's disease, based on exome sequencing and functional studies.

BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through detailed sequencing, genetic association, expression, and functional studies. METHODS: We sequenced whole exomes of 42 unrelated subjects with CD and 5 healthy subjects (controls) and then filtered single nucleotide variants by incorporating association results from meta-analyses of CD GWAS and in silico mutation effect prediction algorithms. We then genotyped 9348 subjects with CD, 2868 subjects with ulcerative colitis, and 14,567 control subjects and associated variants analyzed in functional studies using materials from subjects and controls and in vitro model systems. RESULTS: We identified rare missense mutations in PR domain-containing 1 (PRDM1) and associated these with CD. These mutations increased proliferation of T cells and secretion of cytokines on activation and increased expression of the adhesion molecule L-selectin. A common CD risk allele, identified in GWAS, correlated with reduced expression of PRDM1 in ileal biopsy specimens and peripheral blood mononuclear cells (combined P = 1.6 × 10(-8)). We identified an association between CD and a common missense variant, Val248Ala, in nuclear domain 10 protein 52 (NDP52) (P = 4.83 × 10(-9)). We found that this variant impairs the regulatory functions of NDP52 to inhibit nuclear factor κB activation of genes that regulate inflammation and affect the stability of proteins in Toll-like receptor pathways. CONCLUSIONS: We have extended the results of GWAS and provide evidence that variants in PRDM1 and NDP52 determine susceptibility to CD. PRDM1 maps adjacent to a CD interval identified in GWAS and encodes a transcription factor expressed by T and B cells. NDP52 is an adaptor protein that functions in selective autophagy of intracellular bacteria and signaling molecules, supporting the role of autophagy in the pathogenesis of CD.

Assessment of anti-prothrombin antibodies in thrombosis complicating inflammatory bowel diseases.

PURPOSE: In inflammatory bowel diseases (IBD), risk of thrombosis and production of antibodies are increased. In autoimmune and inflammatory disorders, a role of anti-prothrombin (aPT) antibodies in developing thrombosis has been hypothesised. The aim of the study is to evaluate the prevalence of aPT antibodies in IBD patients, with and without thrombosis. METHODS: Thirty-three IBD patients with thrombosis, 33 IBD patients without thrombosis matched for sex, age, diagnosis and disease activity and 66 sex- and age-matched healthy controls were enrolled. Thrombosis was considered recent when blood sample was obtained within 3 months from the event. RESULTS: Prevalence of aPT antibodies in thrombotic IBD patients (3/33, 9.1 %), non-thrombotic IBD patients (4/33, 12.1 %) and in healthy subjects (3/66, 4.5 %) did not result significantly different (p = 0.377). The prevalence of aPT antibodies was more frequent in ulcerative colitis (6/32, 18.7 %) than in Crohn's disease (1/34, 2.9 %) and healthy controls (p = 0.022). Among thrombotic IBD patients, the prevalence of aPT antibodies was higher in those with recent (2/9, 22.2 %) than in those with previous thrombosis (1/24, 4.2 %) (p = 0.103). All thrombotic IBD patients with aPT antibodies were affected by ulcerative colitis with previous history of deep venous thrombosis. CONCLUSIONS: aPT antibodies do not appear to play a relevant role in thrombosis complicating IBD course. A possible association in ulcerative colitis patients with DVT could not be excluded.

Does smoking influence Crohn's disease in the biologic era? The TABACROHN study.

BACKGROUND: While most studies have found a negative effect of smoking on Crohn's disease (CD) phenotype, more recent data have failed to reproduce this association, which might be due to a current wider use of thiopurines and biologic therapy. The TABACROHN study aimed at defining the impact of smoking on CD in the largest published series. METHODS: This multicenter cross-sectional study included 1170 CD patients. Patients were classified as nonsmokers, current smokers, or former smokers according to their present smoking status. Clinical data regarding disease characteristics, treatment, and complications were collected. RESULTS: Smokers were more frequently under maintenance treatment when compared to nonsmokers. In addition, current smokers presented higher use of biologic drugs compared to nonsmokers. Tobacco exposure and a higher tobacco load were independent predictors of need for maintenance treatment and stenosing phenotype, respectively. CONCLUSIONS: In the era of early and widespread use of immunosuppressants and biologics, tobacco exposure is an independent predictor of need for maintenance treatment, specifically biologic therapy. The wider use of biologics and immunosuppressants could account for the existence of no major differences in disease behavior and complications between nonsmokers and current smokers.

High smoking cessation rate in Crohn's disease patients after physician advice--the TABACROHN Study.

INTRODUCTION: Tobacco smoking has a significant impact on the development of Crohn's disease (CD) and its clinical course, making smoking cessation one of the main goals in CD therapeutic strategy. AIMS: To evaluate the effectiveness of an advice-based smoking cessation strategy among CD patients. METHODS: We have performed a prospective multicenter study which enrolled 408 CD smokers. At inclusion all patients were instructed about the risks of smoking and subsequently followed every 3 months. Each center used additional smoking cessation strategies based on available resources. Urinary cotinine and exhaled carbon monoxide levels were evaluated in a subgroup of patients. RESULTS: Median study follow up was 18 months. 31% of the patients achieved complete smoking cessation and 23% were smoking-free at the end of their follow up with 8% of smoking relapse. Most patients not achieving smoking cessation did not change their smoking habit with only 5% presenting a decrease in tobacco load. 63% of patients willing to quit smoking received help from another specialist, most frequently the pulmonologist (47%). Surprisingly, most patients (88%) tried to quit smoking with no pharmacological therapy and bupropion, varenicline and nicotine replacement treatment were used in few patients. Urinary cotinine and exhaled CO levels tested in a subgroup of patients proved to have a good correlation with the self-reported smoking habit. No predictors of successful smoking cessation were identified. CONCLUSION: Our results underline that an anti-tobacco strategy mostly based on CD patients's education and counseling is feasible and effective in helping patients reach complete abstinence.

Oral locally active steroids in inflammatory bowel disease.

IBD is a chronic and relapsing inflammatory disorder of the gut that demands long-lasting treatment targeting both flare-up periods and maintenance of remission. Oral systemic steroids have been used to induce remission in patients with active IBD for over 50 years due to their potent anti-inflammatory effects. The efficacy of systemic steroids in this setting has been largely demonstrated. However, the wide range of adverse events associated with these drugs has prompted the development of equally effective but less toxic steroid compounds. Currently, topically acting oral steroids are an important therapeutic option for Crohn's disease, ulcerative colitis and microscopic colitis, being oral budesonide and oral beclomethasone established elements of the IBD armamentarium. At present, oral budesonide is the first-line therapy to induce remission in microscopic colitis and mild to moderate ileocaecal CD patients and oral beclomethasone is effective treating mild to moderate UC patients with left-sided or extensive disease. This review aims at evaluating the current role of these compounds in IBD clinical practice.

Genetic factors conferring an increased susceptibility to develop Crohn's disease also influence disease phenotype: results from the IBDchip European Project.

OBJECTIVE: Through genome-wide association scans and meta-analyses thereof, over 70 genetic loci (Crohn's disease (CD) single nucleotide polymorphisms (SNPs)) are significantly associated with CD. We aimed to investigate the influence of CD-SNPs and basic patient characteristics on CD clinical course, and develop statistical models to predict CD clinical course. DESIGN: This retrospective study included 1528 patients with CD with more than 10 years of follow-up from eight European referral hospitals. CD outcomes of interest were ileal (L1), colonic (L2) and ileocolonic disease location (L3); stenosing (B2) or penetrating behaviour (B3); perianal disease; extraintestinal manifestations; and bowel resection. A complicated disease course was defined as stenosing or penetrating behaviour, perianal disease and/or bowel resection. Association between CD-SNPs or patient characteristics and specified outcomes was studied. RESULTS: Several CD-SNPs and clinical characteristics were statistically associated with outcomes of interest. The NOD2 gene was the most important genetic factor, being an independent predictive factor for ileal location (p=2.02 × 10(-06), OR=1.90), stenosing (p=3.16 × 10(-06), OR=1.82) and penetrating (p=1.26 × 10(-02), OR=1.25) CD behaviours, and need for surgery (p=2.28 × e-05, OR=1.73), and as such was also the strongest factor associated with a complicated disease course (p=6.86 × 10(-06), OR=2.96). Immunomodulator (azathioprine/6-mercaptopurine and methotrexate) use within 3 years after diagnosis led to a reduction in bowel stenoses (p=1.48 × 10(-06), OR=0.35) and surgical rate (p=1.71 × 10(-07), OR=0.34). Association between each outcome and genetic scores, created using significant SNPs in the univariate analysis, revealed large differences in the probability of developing fistulising disease (IL23R, LOC441108, PRDM1, NOD2; p=9.64e-4, HR=1.43), need for surgery (IRGM, TNFSF15, C13ORF31, NOD2; p=7.12 × 10(-03), HR=1.35), and stenosing disease (NOD2, JAK2, ATG16L1; p=3.01 × 10(-02), HR=1.29) among patients with low and high score. CONCLUSIONS: This large multicentre cohort study has found several genetic and clinical factors influencing the clinical course of CD. NOD2 and early immunomodulator use are the clinically most meaningful predictors for its clinical course.