Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry.

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Incidencia de la enfermedad inflamatoria intestinal y fenotipo al diagnóstico en 2011: resultados del estudio Epi-IBD 2011 en el área de Vigo / Incidence of inflammatory bowel disease and phenotype at diagnosis in 2011: results of the Epi-IBD 2011 study in the Vigo area

Objetivo: validar la incidencia de la enfermedad inflamatoria intestinal (EII) descrita en el área de Vigo en 2010 en el seno del estudio Epi-IBD, la más alta comunicada en España hasta esa fecha.Métodos: estudio prospectivo, de cohortes incidentes y base poblacional. Se incluyeron todos los pacientes diagnosticados de EII entre el 1-1-2011 y el 31-12-2011 en el área de Vigo.Resultados: se diagnosticaron 100 casos (62 % hombres, edad media de 43,27 años): 49 de colitis ulcerosa (CU), 34 de enfermedad de Crohn (EC) y 17 de EII no clasificada (EIINC). La incidencia (por 100.000 habitantes/año) de la EII fue de 17.56 (EC: 5,97; CU: 8,60; EIINC: 2,98), similar a la descrita en 2010. En la población no pediátrica fue de 19.66 (EC: 6,89; CU: 9,52; EIINC: 3,04). El fenotipo de la EC y la CU fue similar en 2010 y 2011.Conclusiones: este estudio confirma la alta tasa de incidencia de la EII descrita en el área de Vigo en 2010. (AU)

Incidence of inflammatory bowel disease and phenotype at diagnosis in 2011: results of the Epi-IBD 2011 study in the Vigo area.

OBJECTIVE: to validate the incidence of inflammatory bowel disease (IBD) reported in Vigo in 2010 within the Epi-IBD study, which was the highest incidence reported so far in Spain. METHODS: an epidemiological, prospective, population-based inception cohort study. All incident cases of IBD living in the Vigo area at diagnosis from January 1 to December 31, 2011 were included. RESULTS: one hundred patients were diagnosed (62 % men; median age, 43.27 years): 49 with ulcerative colitis (UC), 34 with Crohn's disease (CD), and 17 with IBD unclassified (IBDU). The incidence (per 100,000 inhabitants/year) was 17.56 (CD: 5.97; UC: 8.60; IBDU: 2.98), similar to that reported in 2010. The incidence in the non-pediatric population was 19.66 (CD: 6.89, UC: 9.52; IBDU: 3.04). CD and UC phenotype was similar in 2010 and 2011. CONCLUSION: this study supports the increased incidence of EII in the Vigo area reported in 2010.

Serial Tuberculin Skin Tests Improve the Detection of Latent Tuberculosis Infection in Patients With Inflammatory Bowel Disease.

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

Assessing medication adherence in inflammatory bowel diseases. A comparison between a self-administered scale and a pharmacy refill index.

BACKGROUND: Medication non-adherence in inflammatory bowel disease (IBD) has a negative impact on disease outcome. Different tools have been proposed to assess non-adherence. We aimed to compare a self-administered scale and a pharmacy refill index as a reliable measure of medication adherence and to determine what factors are related to adherence. METHODS: Consecutive non-active IBD outpatients were asked to fill in the self-reported Morisky Medication Adherence Scale (MMAS-8) and the Beliefs about Medication Questionnaire (BMQ). Pharmacy refill data were reviewed from the previous three or six months and the medication possession ratio (MPR) was calculated. Non-adherence was defined as MMAS-8 scores < 6 or MPR < 0.8. RESULTS: Two-hundred and three patients were enrolled (60% ulcerative colitis, 40% Crohn's disease); 51% were men, and the mean age was 46.3 (14) years. Seventy-four per cent of patients were on monotherapy and 26% on combination therapy; altogether, 65% received mesalazine, 46% thiopurines and 16% anti-tumor necrosis factor alfa. Non-adherence rate assessed by MPR was 37% and 22.4% by MMAS-8. Receiver operator curve analysis using a MMAS-8 cut-off of six gave an area under the curve of 0.6 (95% CI 0.5-0.7), p = 0.001. This score had an 85% sensitivity and 34% specificity to predict medication non-adherence, with negative and positive predictive values of 57% and 70% respectively. High scores in the BMQ potential for harm of medication were significantly associated with MPR non-adherence (p = 0.01). CONCLUSION: The accuracy of MMAS-8 to identify medication non-adherence in inactive IBD outpatients in our setting is poor due to a low specificity and a negative predictive value. Psychosocial factors such as beliefs about medication seem to be related to IBD non-adherence.

Early Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIM: Sensitivity of tuberculin skin test [TST] during screening for latent tuberculosis infection [LTBI] is affected by steroid and/or immunosuppressant therapy. The aim of this study was to compare performance of the two-step TST in inflammatory bowel disease patients immediately before anti-tumour necrosis factor [TNF] therapy as part of routine screening for LTBI vs control patients when the TST was carried out at an early stage. METHODS: In this multicentre prospective controlled study, we evaluated the performance of two-step TST with 5-mm threshold. Factors associated with TST results were determined by logistic regression. RESULTS: We evaluated 243 candidates for anti-TNF therapy and 337 control patients. Overall, 105 patients [18.1%] had an induration ≥ 5 mm in the first TST or in TST retest. LTBI was diagnosed in 25% of patients by TST retest. Twenty-eight [11.5%] anti-TNF group patients vs 77 [22.8%] control patients had a positive TST (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.28-0.70; P < 0.001]. In multivariate analysis, positive TST was associated with higher age [OR 2.63, 95% CI 1.21-5.72; P < 0.001] and 5-aminosalicylate therapy [OR 1.86, 95% CI 1.14-3.05; P = 0.013]. Negative TST was associated with steroid therapy [OR 0.36, 95% CI 0.16-0.83; P = 0.016], immunosuppressant therapy [OR 0.36, 95% CI 0.21-0.62; P < 0.001], or steroids + immunosuppressant therapy [OR 0.20, 95% CI 0.07-0.59; P = 0.004]. CONCLUSIONS: The sensitivity of routine TST performed just before starting anti-TNF therapy is low. TST performed at an early stage enables screening in the absence of immunosuppressive treatment and thus maximises the diagnostic yield of TST for detecting LTBI.

Incidence and phenotype at diagnosis of inflammatory bowel disease. Results in Spain of the EpiCom study.

INTRODUCTION: Incidence of inflammatory bowel disease (IBD) is increasing progressively. Few recent epidemiological prospective studies are available in Spain. The Epicom study, a population-based inception cohort of unselected IBD patients developed within the European Crohn's and Colitis Organization, was started in 2010. Vigo is the only Spanish area participating. OBJECTIVE: To describe the incidence of IBD in the Vigo area and the phenotypical characteristics at diagnosis and to compare them with previous data available in Spain. MATERIAL AND METHODS: Epidemiological, descriptive, prospective, and population-based study. All incident cases of IBD during 2010 and living in the Vigo area at diagnosis were included. The Copenhagen Diagnostic criteria were used to define cases. Background population at the start of the study was 579,632 inhabitants. Data were prospectively entered in the EpiCom database. RESULTS: A total of 106 patients were included (57.5% men, median age 39.5 years). Of them 53 were diagnosed of as Crohn's disease (CD), 47 ulcerative colitis (UC) and six IBD unclassified (IBDU). The incidence rate per 100,000 per year for patients aged 15 years or older was 21.4 (10.8 for CD, 9.4 for UC, 1.2 IBDU). Including pediatric population incidence rates were 18.3 (10.3 CD, 8.7 UC, 1.2 IBDU). Median time since onset of symptoms until diagnosis was 2 months. CONCLUSIONS: The incidence rate of IBD in Vigo is the highest compared to former Spanish cohorts, especially in CD patients. Median time since onset of symptoms until diagnosis is relatively short.

Safety and effectiveness of gastric balloons associated with hypocaloric diet for the treatment of obesity.

INTRODUCTION: intragastric balloons provide early satiety and thereby induce short-term weight loss. The aim of this study was to evaluate safety and short and medium-term effectiveness of gastric balloons associated to hypocaloric diet in obesity. MATERIAL AND METHODS: from May 2004 to June 2011 91 obese patients, body mass index (BMI) 45.2 +/- 7.2 kg/m2 were prospectively followed after endoscopic implantation of a gastric balloon associated to restricted diet. Successful therapy was defined as percent loss of total weight (%LTW) > or = 5 % at six months after balloon placement and 6 and 12 months after their withdrawal. All analyses followed intention-to treat principles considering significant p-values < 0.05. RESULTS: we placed 73 fluid-filled balloons (80.2 %) and 18 air-filled ones (19.8 %). Compared to baseline values, at 6-month 73.7 % subjects succeeded, showing significant reductions in weight (13.3 +/- 8.8 kg), BMI (5 +/- 3.4 kg/m2) (p < 0.0001), with % LTW 11 +/- 7 %. Six and twelve months after retrieval 45.1 % and 28.6 % patients reached % LTW > or = 5 %. Short-term and medium-term effectiveness was negatively associated to obesity in first-grade relatives (p = 0.003 and p = 0.04). Higher weight loss 6 months after balloon placement independently predicted medium-term effectiveness (p = 0.0001). Mortality was absent but there were two spontaneous deflations of air-filled balloons and severe withdrawal difficulties in 8 patients, leading to surgery in one case. Retrieval complications associated to air-filled balloons (p = 0.0005). CONCLUSIONS: in obesity, effectiveness of gastric balloons associated to hypocaloric diet decreases over time.Complications occurred mainly in the retrieval endoscopic procedure and related to air-filled balloons.

Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer.

BACKGROUND: The selection of patients for genetic testing to rule out Lynch syndrome is currently based on fulfilment of at least one of the revised Bethesda criteria followed by mismatch repair (MMR) status analysis. A study was undertaken to compare the present approach with universal MMR study-based strategies to detect Lynch syndrome in a large series of patients with colorectal cancer (CRC). METHODS: 2093 patients with CRC from the EPICOLON I and II cohorts were included. Immunohistochemistry for MMR proteins and/or microsatellite instability (MSI) analysis was performed in tumour tissue. Germline MLH1 and MSH2 mutation analysis was performed in patients whose tumours showed loss of MLH1 or MSH2 staining, respectively. MSH6 genetic testing was done in patients whose tumours showed lack of MSH6 expression or a combined lack of MSH2 and MSH6 expression but did not have MSH2 mutations. PMS2 genetic testing was performed in patients showing isolated loss of PMS2 expression. In patients with MSI tumours and normal or not available MMR protein expression, all four MMR genes were studied. RESULTS: A total of 180 patients (8.6%) showed loss of expression of some of the MMR proteins and/or MSI. Four hundred and eighty-six patients (23.2%) met some of the revised Bethesda criteria. Of the 14 (0.7%) patients who had a MMR gene mutation, 12 fulfilled at least one of the revised Bethesda criteria and two (14.3%) did not. CONCLUSIONS: Routine molecular screening of patients with CRC for Lynch syndrome using immunohistochemistry or MSI has better sensitivity for detecting mutation carriers than the Bethesda guidelines.

Efficacy, safety, and tolerance of two types of intragastric balloons placed in obese subjects: a double-blind comparative study.

The intragastric balloon is a temporary treatment for obese patients. Fluid-filled devices have shown efficacy and safety, and are widely used. Recently, although there are no comparative studies between them, an air-filled balloon, Heliosphere® bag, has been proposed. Prospective, double-blind study in 33 patients with morbid and type 2 obesity: 23 female, 43.9±10 years, 120.3±17 kg, and body mass index (BMI) of 44.2±5 kg/m2, placing 18 gastric balloons filled with 960 cm3 of air (Heliosphere® bag) or 15 balloons filled with 700 ml of saline (Bioenterics-BIB®). Both balloons were placed with conscious sedation and removed under general anesthesia 6 months later. Intravenous drugs were given to control symptoms for 48 h. Patients were sent home on a 1000-kcal diet, multivitamin supplements, and oral proton pump inhibitors, and were followed monthly. Complications, symptoms, weight, and quality of life evaluated by the Gastrointestinal Quality of Life Index (GIQLI) scale were recorded. At 6 months, mean weight loss (12.8±8 vs 14.1±8 kg), BMI loss (4.6±3 vs 5.5±3 kg/m2) and percent excess weight loss (27±16 vs.30.2±17) showed no significant differences between both groups. At removal, two Heliosphere® bags were not found in the stomach, and four patients required extraction of the balloon by rigid esophagoscopy or surgery (p=0.02). Tolerance was good in both groups, but early removal occurred in three BIB® (20%) due to vomits and dehydration. The GIQLI total scores remained unchanged. Both balloons achieve a significant weight loss with good tolerance in obese patients. Nevertheless, Heliosphere® bag has severe technical problems that need to be solved before recommending it.