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.

Evaluation of AIF-1 (Allograft Inflammatory Factor-1) as a Biomarker of Crohn's Disease Severity.

Background: Recently, increased tissue levels of AIF-1 have been shown in experimental colitis, supporting its role in intestinal inflammation. Therefore, we studied the levels of AIF-1 in Crohn's disease (CD). Methods: This study included 33 patients with CD (14 men and 19 women) who participated in the PREDICROHN project, a prospective multicenter study of the Spanish Group of Inflammatory bowel disease (GETECCU). Results: This article demonstrates declines with respect to baseline levels of serum AIF-1 in Crohn's disease (CD) patients after 14 weeks of treatment with anti-TNFs. Furthermore, in patients with active CD (HB ≥ 5), serum AIF-1 levels were significantly higher than those in patients without activity (HB ≤ 4). The study of serum AIF-1 in the same cohort, revealed an area under the ROC curve (AUC) value of AUC = 0.66 (p = 0.014), while for the CRP (C-reactive protein), (AUC) value of 0.69 (p = 0.0066), indicating a similar ability to classify CD patients by their severity. However, the combination of data on serum levels of AIF-1 and CRP improves the predictive ability of these analyses for classifying CD patients as active (HB ≥ 5) or inactive (HB ≤ 4). When we used the odds ratio (OR) formula, we observed that patients with CRP > 5 mg/L or AIF-1 > 200 pg/mL or both conditions were 13 times more likely to show HB ≥ 5 (active CD) than were those with both markers below these thresholds. Conclusion: The development of an algorithm that includes serum levels of AIF-1 and CRP could be useful for assessing Crohn's disease severity.

Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved.

Inflammatory bowel diseases (IBD), represented by ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation of the gastrointestinal tract, what leads to diarrhea, malnutrition, and weight loss. Depression of the growth hormone-insulin-like growth factor-1 axis (GH-IGF-1 axis) could be responsible of these symptoms. We demonstrate that long-term treatment (54 weeks) of adult CD patients with adalimumab (ADA) results in a decrease in serum IGF-1 without changes in serum IGF-1 binding protein (IGF1BP4). These results prompted us to conduct a preclinical study to test the efficiency of IGF-1 in the medication for experimental colitis. IGF-1 treatment of rats with DSS-induced colitis has a beneficial effect on the following circulating biochemical parameters: glucose, albumin, and total protein levels. In this experimental group we also observed healthy maintenance of colon size, body weight, and lean mass in comparison with the DSS-only group. Histological analysis revealed restoration of the mucosal barrier with the IGF-1 treatment, which was characterized by healthy quantities of mucin production, structural maintenance of adherers junctions (AJs), recuperation of E-cadherin and ß-catenin levels and decrease in infiltrating immune cells and in metalloproteinase-2 levels. The experimentally induced colitis caused activation of apoptosis markers, including cleaved caspase 3, caspase 8, and PARP and decreases cell-cycle checkpoint activators including phosphorylated Rb, cyclin E, and E2F1. The IGF-1 treatment inhibited cyclin E depletion and partially protects PARP levels. The beneficial effects of IGF-1 in experimental colitis could be explained by a re-sensitization of the IGF-1/IRS-1/AKT cascade to exogenous IGF-1. Given these results, we postulate that IGF-1 treatment of IBD patients could prove to be successful in reducing disease pathology.

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.

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

El registro ENEIDA, promovido por el Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU), fue creado en 2005 por un grupo de gastroenterólogos interesados en mejorar el manejo de los pacientes con enfermedad inflamatoria intestinal. Los objetivos principales del registro fueron facilitar la recogida de datos clínicos de interés para la práctica clínica asistencial, así como la elaboración de estudios colaborativos a partir de datos clínicos y muestras biológicas. En sus 15 años de existencia, ENEIDA ha evolucionado en múltiples aspectos, desde su contenido o su soporte tecnológico hasta el número de centros participantes, para convertirse en uno de los registros de referencia para el estudio y cuidado de los pacientes con enfermedad inflamatoria intestinal, con una producción científica continua y de alta calidad que lo ha situado como ejemplo de explotación científica colaborativa en el ámbito internacional. En este artículo se revisan los objetivos, el diseño, las características estructurales, la monitorización y la explotación científica del registro ENEIDA

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

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.

Usefulness of monitoring antitumor necrosis factor serum levels during the induction phase in patients with Crohn's disease.

AIMS: The aims of this study were (a) to know the kinetics of antitumor necrosis factor (TNF) drug serum levels during the induction phase in patients with Crohn's disease; (b) to identify variables associated with these levels; and (c) to assess the relation between these levels and short-term effectiveness in Crohn's disease patients. METHODS: Patients with Crohn's disease naïve to anti-TNF treatment were prospectively included. Remission was defined as a Crohn's disease activity index (CDAI) score <150 after 14 weeks of treatment. Blood samples were obtained at baseline and at weeks 4, 8, and 14. Adalimumab and infliximab levels were measured, receiver operating characteristic (ROC) curves were constructed, and the area under the ROC curve was calculated. RESULTS: One-hundred fifty patients with Crohn's disease were included, 79 (53%) received infliximab and 71 (47%) had CDAI > 150 at study entry. At week 14, 52 out of 71 patients with CDAI > 150 at baseline (73%) had clinical remission. There were no differences in infliximab levels between patients with and without remission (8 vs. 9.1 µg/mL, P > 0.05) or with and without response (7 vs. 11 µg/mL, P > 0.05) at week 14. There was a trend to higher levels of adalimumab concentration in responders in comparison with nonresponders (13 vs. 6.7 µg/mL, P = 0.05) and in patients who achieved remission in comparison with nonremitters (13.5 vs. 8.4 µg/mL, P = 0.06). In the multivariate analysis, no variable was predictive of short-term remission, including infliximab and adalimumab serum levels. CONCLUSION: Determining anti-TNF serum levels during the induction phase is not useful for predicting short-term remission in patients with Crohn's disease.

Functional rare variants influence the clinical response to anti-TNF therapy in Crohn's disease.

BACKGROUND: The effect of low-frequency functional variation on anti-tumor necrosis factor alpha (TNF) response in Crohn's disease (CD) patients remains unexplored. The objective of this study was to investigate the impact of functional rare variants in clinical response to anti-TNF therapy in CD. METHODS: CD anti-TNF naïve patients starting anti-TNF treatment due to active disease [Crohn's Disease Activity Index (CDAI > 150)] were included. The whole genome was sequenced using the Illumina Hiseq4000 platform. Clinical response was defined as a CDAI score <150 at week 14 of anti-TNF treatment. Low-frequency variants were annotated and classified according to their damaging potential. The whole genome of CD patients was screened to identify homozygous loss-of-function (LoF) variants. The TNF signaling pathway was tested for overabundance of damaging variants using the SKAT-O method. Functional implication of the associated rare variation was evaluated using cell-type epigenetic enrichment analyses. RESULTS: A total of 41 consecutive CD patients were included; 3250 functional rare variants were identified (2682 damaging and 568 LoF variants). Two homozygous LoF mutations were found in HLA-B and HLA-DRB1 genes associated with lack of response and remission, respectively. Genome-wide LoF variants were enriched in epigenetic marks specific for the gastrointestinal tissue (colon, p = 4.11e-4; duodenum, p = 0.011). The burden of damaging variation in the TNF signaling pathway was associated with response to anti-TNF therapy (p = 0.016); damaging variants were enriched in epigenetic marks from CD8+ (p = 6.01e-4) and CD4+ (p = 0.032) T cells. CONCLUSIONS: Functional rare variants are involved in the response to anti-TNF therapy in CD. Cell-type enrichment analysis suggests that the gut mucosa and CD8+ T cells are the main mediators of this response.

Endoscopic follow-up and therapeutic attitude after ileocolonic resection in a nationwide Spanish cohort of Crohn's disease patients: the Practicrohn study.

Background: In patients with Crohn's disease (CD), endoscopic recurrence precedes clinical recurrence after ileocolonic resection. Guidelines recommend ileocolonoscopy within the first year after surgery. The study examined endoscopic monitoring and treatment decisions in CD patients in a real-world setting. Methods: The Practicrohn study involved adult patients from 26 Spanish hospitals who underwent ileocolonic resection with anastomosis from 2007 to 2010. Medical records data were collected retrospectively from diagnosis to index surgery and up to 5 years after surgery. Results: Of 314 analyzed patients, 262 (83%) underwent endoscopic evaluation, but only 30% (n = 95) had planned endoscopy as part of follow-up within the first year after surgery. An upward trend was observed in the proportion of endoscopies performed or planned within the first year after surgery across the selection period. More patients with than without endoscopic recurrence in the first year after surgery had a medication change, mainly for endoscopic activity in the absence of clinical symptoms (54 vs 13%; p = 0.02). Conclusions: Between 2007 and 2010, endoscopic monitoring of patients within the first year after CD-related surgery was less than adequate based on current standards, but showed improvement. Medication changes were in general agreement with current guideline recommendations. This work was presented as a poster (number P686) by M. Barreiro-de Acosta et al. at ECCO (European Crohn's and Colitis Organisation) '18 in Vienna, Austria, 14-17 February 2018.

Perioperative management and early complications after intestinal resection with ileocolonic anastomosis in Crohn's disease: analysis from the PRACTICROHN study.

BACKGROUND: This study is aimed at describing the prevalence of and risk factors associated with early post-operative complications after Crohn's disease-related intestinal resection. METHODS: This was a retrospective analysis of data from the PRACTICROHN cohort. Adult Crohn's disease patients who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010 were included. The complications evaluated included death, ileus, anastomotic leak, abscess, wound infection, catheter-related infection, digestive bleeding and other extra-abdominal infections that occurred in the 30 days after surgery. RESULTS: A total of 364 patients (median age at surgery 38 years and 50% men) were included. Indication for surgery was: stricturing disease (46.4%), penetrating disease (31.3%), penetrating and stricturing disease (14.0%) or resistance to medical treatment (5.8%). Early complications were recorded in 100 (27.5%) patients, with wound infection, intra-abdominal abscess and anastomotic leakage being the most frequent complications. Median hospitalization duration was 16 days for patients with complications vs. 9 days without complications (P < 0.001). Complications were more common among patients with penetrating disease (36/114, 31.6%) and those refractory to treatment (9/21, 42.9%) compared with stricturing disease (45/169, 26.6%) or stricturing + penetrating disease (6/51, 11.8%) (P = 0.040). The rate of complications was higher among patients with diagnosis made at the time of surgery (15/31, 48.4%) compared with the rest (85/331, 25.7%) (P = 0.013). Medication received at the time of surgery did not affect the rate of complications. CONCLUSIONS: Almost a quarter of patients developed early complications after intestinal resection. Penetrating disease and urgent surgery were associated with an increased risk of complications.

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.

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial.

BACKGROUND: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment versus those who continue treatment. METHODS: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn's disease or ulcerative colitis who have achieved clinical remission for ⩾6 months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1 year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. RESULTS: Enrolment began in 2016, and the study is expected to end in 2020. CONCLUSIONS: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. CLINICAL TRIAL REFERENCE NUMBER: EudraCT 2015-001410-10.

Management and outcomes of patients with Crohn's disease with first vs multiple surgeries: results from the PRACTICROHN study.

BACKGROUND: Surgery in Crohn's disease (CD) may be associated with poor prognosis and clinical and surgical recurrence. The aim of this study was to describe and compare the post-operative management and outcomes of patients with CD who underwent first vs recurrent surgeries. METHODS: Observational study that included adult CD patients from 26 Spanish hospitals who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010. Data were retrospectively collected from the medical records. RESULTS: Data from 314 patients were analysed, of whom 262 (83%) underwent first surgery and 52 (17%) referred to previous CD surgeries. Baseline characteristics were similar between the two groups except for a higher rate of stricturing behavior at diagnosis among re-operated patients (P = 0.03). After surgery, a higher proportion of re-operated patients received prophylactic treatment with immunomodulators compared with patients with first surgery (P = 0.04). In re-operated patients, time to clinical recurrence was not associated with the fact of receiving or not prophylaxis, whereas, in patients with first surgery, recurrence-free survival was greater when prophylaxis was received (P = 0.03). CONCLUSIONS: After surgery, a higher proportion of patients with previous surgeries received prophylactic treatment with immunomodulators compared with patients with first surgery. Although prophylactic treatment was beneficial for preventing clinical recurrence in patients operated on for the first time, it did not significantly reduce the risk of further recurrence in patients with previous surgeries. This suggests that effective prophylactic therapies are still needed in this subset of patients.

Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry.

BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.

Granulocyte and monocyte apheresis in inflammatory bowel disease: The patients' point of view / Granulocito-monocito aféresis en la enfermedad inflamatoria intestinal: el punto de vista de los pacientes

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

INTRODUCCIÓN: La leucocitoaféresis constituye el principal tratamiento no farmacológico para la enfermedad inflamatoria intestinal (EII), pero no conocemos su grado de aceptación por los pacientes en nuestro entorno. OBJETIVO: Conocer la percepción de los pacientes sobre la leucocitoaféresis en la práctica clínica en España. MÉTODOS: Se ofreció un cuestionario de 14 preguntas a los pacientes ambulatorios tratados con leucocitoaféresis en 5 unidades de EII en España. RESULTADOS: Cincuenta y dos pacientes respondieron el cuestionario (88% colitis ulcerosa, 12% enfermedad de Crohn; 44% mujeres, 35 años [RIQ: 23-51]). La leucocitoaféresis fue bien tolerada de forma global y con un alto grado de aceptación. La mayoría de pacientes no percibía la duración de las sesiones como una limitación. En cambio, los síntomas digestivos eran una preocupación habitual, tanto para acudir al tratamiento como durante las sesiones. Un 44% estaban satisfechos con la efectividad del tratamiento. El 60% contestaron que estaban satisfechos con la técnica de forma global, pero esto estaba influenciado por la respuesta clínica que habían experimentado. Un 82% estarían dispuestos a ser tratados de nuevo con la técnica, independientemente de la respuesta al tratamiento. CONCLUSIONES: La leucocitoaféresis es una técnica bien tolerada y aceptada por los pacientes con EII. A pesar de que no encontramos diferencias según el tipo de EII o la pauta de tratamiento, sí encontramos una percepción diferente según la efectividad de la técnica

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.

Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

BACKGROUND AND AIMS: Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. METHODS: This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. RESULTS: In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. CONCLUSIONS: In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

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

Introducción: El déficit de hierro sin anemia asociada (DHSA) es un hallazgo frecuente en los pacientes no ingresados con enfermedad inflamatoria intestinal (EII), incluso en mayor proporción que la anemia. Sin embargo, no existen datos concluyentes de su presencia en nuestro medio ni del posible deterioro que conlleva en la calidad de vida relacionada con la salud (CVRS). Los objetivos de este trabajo fueron: establecer la prevalencia del DHSA, identificar posibles factores asociados y medir su impacto en la CVRS. Material y métodos: Se incluyeron 127 pacientes con EII, de manera consecutiva, en medio extrahospitalario en un estudio observacional, descriptivo, de corte transversal. Se definió DHSA como niveles de ferritina ≤30 ng/ml en ausencia de actividad inflamatoria o <100 ng/ml en su presencia, con índice de saturación de transferrina ≤16%, junto a niveles normales de hemoglobina. Se evaluó la CVRS mediante dos cuestionarios: CVEII-9 para los síntomas relacionados con EII, y FACIT-F para medir la presencia de fatiga, considerándola extrema ante una puntuación ≤ 30 puntos. Resultados: La prevalencia del DHSA fue del 37%. El sexo femenino (OR=2,9; p=0,015) y la presencia de actividad inflamatoria (OR=9,4; p=0,001) fueron las variables asociadas con su aparición. Los pacientes con DHSA presentaron cuestionarios de CVRS con menores puntuaciones de forma global; registrando una caída de 6,6 (p<0,001) y 4,3 (p=0,037) puntos en CVEII-9 y FACIT-F, respectivamente. Además, se observó un incremento en la presencia de fatiga extrema del 29,4%. Conclusión: La prevalencia de DHSA es considerable en los pacientes con EII en el ámbito extrahospitalario. Se asocia al sexo femenino y a la actividad inflamatoria, y supone un claro impacto negativo en la CVRS. Es necesaria una actitud más activa para el tratamiento de esta complicación (AU)

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 (AU)