The Risk of Developing Disabling Crohn's Disease: Validation of a Clinical Prediction Rule to Improve Treatment Decision Making.

BACKGROUND: Crohn's disease (CD) is characterized by the development of complications over the course of the disease. It is crucial to identify predictive factors of disabling disease, in order to target patients for early intervention. We evaluated risk factors of disabling CD and developed a prognostic model. METHODS: In total, 511 CD patients were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to identify demographic, clinical, and biological risk factors. A predictive nomogram model was developed in a subgroup of patients with noncomplicated CD (inflammatory pattern and no perianal disease). RESULTS: The rate of disabling CD within 5 years after diagnosis was 74.6%. Disabling disease was associated with gender, location of disease, requirement of steroids for the first flare, and perianal lesions. In the subgroup of patients (310) with noncomplicated CD, the rate of disabling CD was 80%. In the multivariate analysis age at onset <40 years (OR = 3.46, 95% confidence interval [CI] = 1.52-7.90), extensive disease (L3/L4) (OR = 2.67, 95% CI = 1.18-6.06), smoking habit (OR = 2.09, 95% CI = 1.03-4.27), requirement of steroids at the first flare (OR = 2.20, 95% CI = 1.09-4.45), and albumin (OR = 0.59, 95% CI = 0.36-0.96) were associated with development of disabling disease. The developed predictive nomogram based on these factors presented good discrimination, with an area under the receiver operating characteristic curve of 0.723 (95% CI: 0.670-0.830). CONCLUSION: We identified predictive factors of disabling CD and developed an easy-to-use prognostic model that may be used in clinical practice to help identify patients at high risk and address treatment effectively.

Development of a Prediction Model for Short-Term Remission of Patients with Crohn's Disease Treated with Anti-TNF Drugs.

Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn's disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (p ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (p < 0.001), whose differential expression was confirmed by ELISA (p = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.

Fendrix vs Engerix-B for Primo-Vaccination Against Hepatitis B Infection in Patients With Inflammatory Bowel Disease: A Randomized Clinical Trial.

INTRODUCTION: To compare Engerix-B and Fendrix hepatitis B virus for primo vaccination in inflammatory bowel disease (IBD). METHODS: Patients with IBD were randomized 1:1 to receive Engerix-B double dose or Fendrix single dose at months 0, 1, 2, and 6. Anti-HBs titers were measured 2 months after the third and fourth doses. Response to vaccination was defined as anti-HBs ≥100 UI/L. Anti-HBs titers were measured 2 months after the third and fourth doses and again at 6 and 12 months after the fourth dose. RESULTS: A total of 173 patients were randomized (54% received Engerix-B and 46% Fendrix). Overall, 45% of patients responded (anti-HBs ≥100 IU/L) after 3 doses and 71% after the fourth dose. The response rate after the fourth dose was 75% with Fendrix vs 68% with Engerix-B (P = 0.3). Older age and treatment with steroids, immunomodulators, or anti-tumor necrosis factor were associated with a lower probability of response. However, the type of vaccine was not associated with the response. Anti-HBs titer negativization occurred in 13% of patients after 6 months and 20% after 12 months. Anti-HBs ≥100 IU/L after vaccination was the only factor associated with maintaining anti-HBs titers during follow-up. DISCUSSION: We could not demonstrate a higher response rate of Fendrix (single dose) over Engerix-B (double dose). A 4-dose schedule is more effective than a 3-dose regimen. Older age and treatment with immunomodulators or anti-tumor necrosis factors impaired the success. A high proportion of IBD patients with protective anti-HBs titers after vaccination loose them over time. The risk of losing protective anti-HBs titers is increased in patients achieving anti-HBs <100 IU/L after the vaccination.

The ENEIDA registry (Nationwide study on genetic and environmental determinants of inflammatory bowel disease) by GETECCU: Design, monitoring and functions. / El registro ENEIDA (Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales) de GETECCU: diseño, monitorización y funciones.

The ENEIDA registry, promoted by the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU), was created in 2005 by a group of gastroenterologists interested in improving the management of patients with inflammatory bowel disease. The main objectives of the registry were to facilitate the collection of clinical data of interest for clinical care practice, as well as to carry out collaborative studies using clinical data and biological samples. In its 15 years of existence, ENEIDA has evolved in many aspects, from its content or technological support to the number of participating centres, to become one of the reference registries for the study and care of patients with inflammatory bowel disease, with a continuous and high quality scientific production that has positioned it as an example of collaborative scientific exploitation at an international level. This article reviews the objectives, design, structural characteristics, monitoring and scientific exploitation of the ENEIDA registry.

Genetic association between CD96 locus and immunogenicity to anti-TNF therapy in Crohn's disease.

The production of antibodies to anti-tumor necrosis factor alpha (TNF) agents is one of the main causes of treatment failure in Crohn's disease (CD). To date, however, the contribution of genetics to anti-TNF immunogenicity in CD is still unknown. The objective of the present study was to identify genetic variation associated with anti-TNF immunogenicity in CD. We performed a two-stage genome-wide association study in a cohort of 96 and 123 adalimumab-treated patients, respectively. In the discovery stage, we identified a genome-wide significant association between the CD96 locus and the production of antibodies to anti-TNF treatment (P = 1.88e-09). This association was validated in the replication stage (P < 0.05). The risk allele for anti-TNF immunogenicity was found to be also associated with a lack of response to anti-TNF therapy (P = 0.019). These findings represent an important step toward the understanding of the immunogenicity-based mechanisms that underlie anti-TNF response in CD.

Serial semi-quantitative measurement of fecal calprotectin in patients with ulcerative colitis in remission.

BACKGROUND: Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (UC), and it is a good predictor of relapse. However, its use in clinical practice is constrained by the need for the patient to deliver stool samples, and for their handling and processing in the laboratory. The availability of hand held devices might spread the use of FC in clinical practice. OBJECTIVES: To evaluate the usefulness of a rapid semi-quantitative test of FC in predicting relapse in patients with UC in remission. MATERIALS AND METHODS: Prospective, multicenter study that included UC patients in clinical remission for ≥6 months on maintenance treatment with mesalamine. Patients were evaluated clinically and semi-quantitative FC was measured using a monoclonal immunochromatography rapid test at baseline and every three months until relapse or 12 months of follow-up. RESULTS: One hundred and ninety-one patients had at least one determination of FC. At the end of follow-up, 33 patients (17%) experienced clinical relapse. Endoscopic activity at baseline (p = .043) and having had at least one FC > 60 µg/g during the study period (p = .03) were associated with a higher risk of relapse during follow-up. We obtained a total of 636 semi-quantitative FC determinations matched with a three-month follow-up clinical assessment. Having undetectable FC was inversely associated with early relapse (within three months), with a negative predictive value of 98.6% and a sensitivity of 93.9%. CONCLUSIONS: Serial, rapid semi-quantitative measurement of FC may be a useful, easy and cheap monitoring tool for patients with UC in remission.

Prevalence of iron deficiency without anaemia in inflammatory bowel disease and impact on health-related quality of life. / Prevalencia de déficit de hierro sin anemia en la enfermedad inflamatoria intestinal y su impacto en la calidad de vida.

INTRODUCTION: Iron deficiency without anaemia (IDWA) is commonly found in outpatients with inflammatory bowel disease (IBD) in an even higher proportion than anaemia. However, its true prevalence and possible impact on health-related quality of life (HRQoL) are unknown. The objectives of this study were: to establish the prevalence of IDWA, identify possible associated factors and measure their impact on HRQoL. MATERIAL AND METHODS: 127 patients with IBD in an outpatient setting were consecutively included in an observational, descriptive, cross-sectional study. IDWA was defined as ferritin levels of <100 ng/ml with inflammatory activity or ≤30 ng/ml without it, with transferrin saturation of ≤16%, and with normal haemoglobin levels. HRQoL was assessed using two questionnaires: the IBDQ-9 for symptoms related to IBD and the FACIT-F to measure the presence of fatigue. Fatigue was considered extreme with a score of ≤30 points. RESULTS: The prevalence of IDWA was 37%. Variables associated with its occurrence were female gender (OR=2.9; p=.015) and the presence of inflammatory activity (OR=9.4; p=.001). Patients with IDWA presented HRQoL questionnaires with lower overall scores; decreases of 6.6 (p<.001) and 4.3 (p=.037) points in the IBDQ-9 and the FACIT-F were recorded, respectively. In addition, an increase of 29.4% in the presence of extreme fatigue was observed. CONCLUSION: The prevalence of IDWA is considerable in outpatients with IBD. IDWA is associated with female gender and inflammatory activity. It has a clear negative impact on HRQoL. A more active approach is needed to treat this complication.

Granulocyte and monocyte apheresis in inflammatory bowel disease: The patients' point of view.

BACKGROUND: Granulocyte and monocyte apheresis is the main non-pharmacological treatment for inflammatory bowel disease (IBD), but we do not know how well accepted it is by patients in our setting. AIM: To determine how granulocyte and monocyte apheresis is perceived by patients in clinical practice in Spain. METHODS: Outpatients treated with granulocyte and monocyte apheresis in five IBD Units in Spain were asked to fill in a 14-item questionnaire. RESULTS: Fifty-two patients completed the questionnaire (88% ulcerative colitis, 12% Crohn's disease; 44% female; age 35 years [IQR 23-51]). Granulocyte and monocyte apheresis was generally well tolerated and well accepted. Very few of the participants regarded the length of the sessions as a limitation. The gastrointestinal symptoms, however, were a frequent concern, both in terms of attending to receive treatment and during the sessions. Overall, 44% were satisfied with the treatment effectiveness. Sixty percent (60%) claimed to be satisfied with the therapy overall, but this was influenced by the patients' clinical response to the therapy. Eighty-two percent (82%) of participants said they would agree to be treated with this technique again in the future, regardless of the response to the treatment. CONCLUSIONS: Granulocyte and monocyte apheresis is well tolerated and accepted by patients with IBD. Although we found no significant differences according to type of IBD or apheresis regimen, patient perception was affected by clinical effectiveness.

Clinical status, quality of life, and work productivity in Crohn's disease patients after one year of treatment with adalimumab.

OBJECTIVE: Clinical trials have shown the efficacy of adalimumab in Crohn's disease, but the outcome in regular practice remains unknown. The aim of the study was to examine clinical status, quality of life, and work productivity of Crohn's disease patients receiving adalimumab for one year in the context of usual clinical practice. MATERIAL AND METHODS: This was a prospective, observational study with a one-year follow-up. After baseline, Crohn's disease patients were evaluated at 1, 3, 6, 9, and 12 months after starting treatment with adalimumab. Outcome variables included: clinical status (measured with CDAI), quality of life (measured with EuroQoL-5D and IBDQ), and work productivity (measured with WPAI questionnaire). These outcome variables were compared using the Student's t test or Wilcoxon test for paired comparison data according to the data distribution. Statistical significance was set at two-sided p < 0.05. RESULTS: The sample was composed of 126 patients (age [mean] 39.1 ± [standard deviation] 13.8 years; 51% male). Significant changes were observed during the follow-up period: CDAI decreased from [median] 194 ([25-75 percentiles] 121-269) to 48.2 (10.1-122.0) (p < 0.05); the EuroQoL-5D increased from 0.735 (0.633-0.790) to 0.797 (0.726-1.000) (p < 0.05); the EuroQoL-5D visual analogue scale increased from 50.0 (40-70) to 80.0 (60-90); (p < 0.05) and the IBDQ increased from 56.7 (51.6-61.5) to 67.5 (60.1-73.6) (p < 0.05). The total work productivity impact decreased from 53% to 24% (p < 0.05). CONCLUSIONS: In regular practice, adalimumab is clinically effective in the treatment of Crohn's disease patients and results in a significant improvement in quality of life and work productivity.

Evolution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission. / Evolución tras el intercambio a infliximab biosimilar en pacientes con enfermedad inflamatoria intestinal en remisión clínica.

BACKGROUND AND AIM: The biosimilar of infliximab (CT-P13) has been approved for the same indications held by the infliximab reference product (Remicade®); however, there are few clinical data on switching in inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy, safety, bioavailability profile and factors associated with relapse after switching to biosimilar infliximab in IBD patients in clinical remission. MATERIAL AND METHOD: Observational study with IBD patients treated with Remicade® for at least 6 months and in clinical remission for at least 3 months who switched to infliximab biosimilar. The incidence of relapse, adverse effects and possible changes in drug bioavailability (trough level and antidrug antibodies) were evaluated. RESULTS: Thirty six patients were included (63.9% CD) with a mean follow-up of 8.4 months (SD±3.5). The 13.9% had clinical relapse. The longer clinical remission time before switching (HR=0.54, 95% CI=0.29-0.98, P=.04) and detectable infliximab levels at the time of switching (HR=0.03, 95% CI=0.001-0.89, P=.04) were associated with a lower risk of relapse. No differences were found between infliximab levels at the time of switching and at weeks 8 and 16 (P=.94); 8.3% of the patients had some adverse event, requiring the suspension of biosimilar in one patient for severe pneumonia. CONCLUSION: Switching to biosimilar infliximab in a real-life cohort of IBD patients in clinical remission did not have a significant impact on short-term clinical outcomes. The factors associated with relapse were similar to those expected in patients continuing with Remicade®.

A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis.

The genetic analysis of ulcerative colitis (UC) has provided new insights into the etiology of this prevalent inflammatory bowel disease. However, most of the heritability of UC (>70%) has still not been characterized. To identify new risk loci for UC we have performed the first genome-wide association study (GWAS) in a Southern European population and undertaken a meta-analysis study combining the newly genotyped 825 UC patients and 1525 healthy controls from Spain with the six previously published GWAS comprising 6687 cases and 19 718 controls from Northern-European ancestry. We identified a novel locus with genome-wide significance at 6q22.1 [rs2858829, P = 8.97 × 10(-9), odds ratio (OR) (95% confidence interval, CI] = 1.12 (1.08-1.16)] that was validated with genotype data from a replication cohort of the same Southern European ancestry consisting in 1073 cases and 1279 controls [combined P = 7.59 × 10(-10), OR (95% CI) = 1.12 (1.08-1.16)]. Furthermore, we confirmed the association of 33 reported associations with UC and we nominally validated the GWAS results of nine new risk loci (P < 0.05, same direction of effect). SNP rs2858829 lies in an intergenic region and is a strong cis-eQTL for FAM26F gene, a gene that is shown to be selectively upregulated in UC colonic mucosa with active inflammation. Our results provide new insight into the genetic risk background of UC, confirming that there is a genetic risk component that differentiates from Crohn's Disease, the other major form of inflammatory bowel disease.

Identification of risk loci for Crohn's disease phenotypes using a genome-wide association study.

BACKGROUND & AIMS: Crohn's disease is a highly heterogeneous inflammatory bowel disease comprising multiple clinical phenotypes. Genome-wide association studies (GWASs) have associated a large number of loci with disease risk but have not associated any specific genetic variants with clinical phenotypes. We performed a GWAS of clinical phenotypes in Crohn's disease. METHODS: We genotyped 576,818 single-nucleotide polymorphisms in a well-characterized cohort of 1090 Crohn's disease patients of European ancestry. We assessed their association with 17 phenotypes of Crohn's disease (based on disease location, disease behavior, disease course, age at onset, and extraintestinal manifestations). A total of 57 markers with strong associations to Crohn's disease phenotypes (P < 2 × 10(-4)) were subsequently analyzed in an independent replication cohort of 1296 patients of European ancestry. RESULTS: We replicated the association of 4 loci with different Crohn's disease phenotypes. Variants in MAGI1, CLCA2, 2q24.1, and LY75 loci were associated with a complicated stricturing disease course (Pcombined = 2.01 × 10(-8)), disease location (Pcombined = 1.3 × 10(-6)), mild disease course (Pcombined = 5.94 × 10(-7)), and erythema nodosum (Pcombined = 2.27 × 10(-6)), respectively. CONCLUSIONS: In a GWAS, we associated 4 loci with clinical phenotypes of Crohn's disease. These findings indicate a genetic basis for the clinical heterogeneity observed for this inflammatory bowel disease.

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.

Initial experience with golimumab in clinical practice for ulcerative colitis.

BACKGROUND: Golimumab is a TNF-blocking agent indicated as a second-line therapy in ulcerative colitis. PURPOSE: To research the effectiveness and safety of golimumab in patients with ulcerative colitis in clinical practice. METHODS: Retrospective study of the effectiveness and safety of golimumab in patients with ulcerative colitis. All patients received golimumab 200 mg subcutaneously at week 0, and golimumab 100 mg subcutaneously at week 2. After the induction treatment, each patient received 50 mg sc. every 4 weeks in patients with body weight less than 80 kg, and 100 mg every 4 weeks in patients with body weight greater than or equal to 80 kg. RESULTS: Study of a group of 23 ulcerative colitis patients, 7 of whom were naive to any anti-TNF therapy, and 16 patients who had previously been treated with an anti-TNF agent other than golimumab (non-naive patients). The average treatment time with golimumab was 14.3 weeks. Globally, withdrawal of corticosteroids was observed in 74% of cases. Clinical response was observed in 85.5% of patients who had not received biological treatment previously, and in patients who had previously received biological treatment the response rate was 75%. CONCLUSIONS: In this short study, golimumab seems to be an alternative treatment in naive and non-naive anti-TNF ulcerative colitis patients. It is also a safe therapy, given that there were no adverse effects in the patients studied.

Adherence to a predefined vaccination program in patients with inflammatory bowel disease.

INTRODUCTION: The application of vaccination programs in patients with inflammatory bowel disease (IBD) is heterogeneous and generally deficient. As a result, adherence in these patients to a predefined vaccination program has not been clearly established. The aim of this study was to estimate adherence to a predefined vaccination program among patients with IBD and to identify the factors that may predict poor adherence. METHODS: All patients diagnosed with IBD and followed-up between January and March 2012 were referred to the Department of Preventive Medicine for evaluation of their immune status (with serological testing for hepatitis A, B and C viruses, varicella-zoster virus, mumps, rubella and measles), followed by vaccination based on the test results obtained and on the patient's vaccination history. The percentage of adherence to the vaccination program was determined, along with the factors associated with low adherence. RESULTS: A total of 153 patients with IBD (ulcerative colitis in 50.3% and Crohn's disease in 49.7%) were included (45.1% men and 54.9% women; mean age 43.30±14.19 years, range 17-83). The vaccination program adherence rate was 84.3%. The factors associated with poor adherence were drugs related to IBD (patients not receiving immunosuppressants and/or biological agents showed lower adherence than those receiving these treatments; p=0.021), adherence to medical treatment (poor adherence to treatment was also associated with poor adherence to vaccination; p=0.016), and marital status (single, divorced or separated patients showed lower adherence than married individuals; p=0.015). CONCLUSION: Adherence to vaccination is acceptable among patients with IBD. However, specific actions, such as optimization of patient information on the disease and emphasis on the need for adequate vaccination, are to improve adherence.

Infliximab Dose Escalation as an Effective Strategy for Managing Secondary Loss of Response in Ulcerative Colitis.

BACKGROUND: The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated. AIMS: To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC. METHODS: This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis. RESULTS: Seventy-nine patients were included. Fifty-four patients (68.4%) achieved short-term clinical response and 41 patients (51.9%) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8%) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.12-0.49; p < 0.001]. During a median follow-up of 24 months (IQR 13-34), 9 patients (11.4%) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95% CI 0.03-0.69; p < 0.007). CONCLUSIONS: In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70% of patients. In the long term, 58% of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86% reduction in the relative risk of colectomy.

[Two-year incidence of new immune-mediated inflammatory diseases in patients with inflammatory bowel disease: A study in the AQUILES cohort]. / Incidencia a los 2 años de nuevas enfermedades inflamatorias mediadas por inmunidad en la cohorte de pacientes con enfermedad inflamatoria intestinal del estudio AQUILES.

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

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.

[Immune-mediated inflammatory diseases in patients with inflammatory bowel disease. Baseline data from the Aquiles study]. / Enfermedades inflamatorias mediadas por inmunidad en pacientes con enfermedad inflamatoria intestinal. Datos basales del estudio Aquiles.

OBJECTIVE: To determine the prevalence of immune-mediated inflammatory diseases (IMID) in a cohort of patients with inflammatory bowel disease (IBD) enrolled in hospital gastroenterology outpatients units for the AQUILES study, a prospective 2-year follow-up study. MATERIAL AND METHODS: We included patients ≥18 years old with a prior or new diagnosis of IBD (Crohn disease [CD], ulcerative colitis [UC] or indeterminate colitis). Diagnoses were collected in a cross-sectional manner from the clinical records at enrollment of a new patient in the study. RESULTS: We included 526 patients (mean age 40.2 years; 47.3% men, 52.7% women), 300 with CD (57.0%), 218 with UC (41.4%) and 8 with indeterminate colitis. Other types of IMID were present in 71 patients (prevalence: 13.5%, 95% CI: 10.8-16.7): 47 were spondyloarthropathies (prevalence: 8.9%); 18 psoriasis (3.4%); 5 pyoderma gangrenosum (1.0%), and 11 uveitis (2.1%). The prevalence of IMID was higher in patients with CD than in those with UC (17.0% [95% CI: 13.2-21.7] vs 9.2% [95% CI: 6.0-13.8], p=0.011). In the multivariate analysis, the variables associated with the presence of IMID were diagnosis of CD (OR=1.8 [95% CI: 1.1-3.2]) and duration of IBD ≥4 years (OR=2.1 [95% CI: 1.1-4.1] in those with disease duration 4-8 years, and OR=2.1 [95% CI: 1.2-3.9] in those with ≥8 years vs. <4 years). CONCLUSIONS: In the cohort of patients with IBD in the AQUILES study, 13.5% had another IMID, with a higher prevalence in patients with CD and>4 years since disease onset.

A genome-wide association study on a southern European population identifies a new Crohn's disease susceptibility locus at RBX1-EP300.

OBJECTIVE: Genome-wide association studies (GWAS) have identified multiple risk loci for Crohn's disease (CD). However, the cumulative risk exerted by these loci is low, and the likelihood that additional, as-yet undiscovered loci contribute to the risk of CD is very high. We performed a GWAS on a southern European population to identify new CD risk loci. DESIGN: We genotyped 620 901 genome markers on 1341 CD patients and 1518 controls from Spain. The top association signals representing new candidate risk loci were subsequently analysed in an independent replication cohort of 1365 CD patients and 1396 controls. RESULTS: We identified a genome-wide significant association on chromosome 22q13.2 in the intergenic region between the RBX1 and EP300 genes (single nucleotide polymorphism rs4820425, OR 1.27, 95% CI 1.17 to 1.38, p=3.42E-8). We also found suggestive evidence for the association of the IFNGR2 (21q22.11), FOXP2 (7q31), MACROD2 (20p12.1) and AIF1 (6p21.3) loci with CD risk. CONCLUSIONS: In this GWAS performed on a southern European cohort, we have identified a new risk locus for CD between RBX1 and EP300. This study demonstrates that using populations of different ancestry is a useful strategy to identify new risk loci for CD.