Regulation of the Intestinal Extra-Adrenal Steroidogenic Pathway Component LRH-1 by Glucocorticoids in Ulcerative Colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and can be treated with glucocorticoids (GC), although some patients are unresponsive to this therapy. The transcription factor LRH-1/NR5A2 is critical to intestinal cortisol production (intestinal steroidogenesis), being reduced in UC patients. However, the relationship between LRH-1 expression and distribution with altered corticosteroid responses is unknown. To address this, we categorized UC patients by their steroid response. Here, we found that steroid-dependent and refractory patients presented reduced glucocorticoid receptor (GR)-mediated intestinal steroidogenesis compared to healthy individuals and responder patients, possibly related to increased colonic mucosa GR isoform beta (GRß) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GRiKO) dextran sodium sulfate (DSS)-colitis mice model presented decreased epithelial LRH-1 expression, whilst it increased in the lamina propria compared to DSS-treated control mice. Mechanistically, GR directly induced NR5A2 gene expression in CCD841CoN cells and human colonic organoids. Furthermore, GR bound to two glucocorticoid-response elements within the NR5A2 promoter in dexamethasone-stimulated CCD841CoN cells. We conclude that GR contributes to intestinal steroidogenesis by inducing LRH-1 in epithelial cells, suggesting LRH-1 as a potential marker for glucocorticoid-impaired response in UC. However, further studies with a larger patient cohort will be necessary to confirm role of LRH-1 as a therapeutic biomarker.

Infliximab en enfermedad inflamatoria intestinal. ¿Es necesario premedicar? / Infliximab in inflammatory bowel disease. Is premedication necessary?

Introducción: El uso de infliximab (IFX) en enfermedad inflamatoria intestinal (EII) se ha asociado con un riesgo de 1-6% de reacciones a la infusión. La utilidad de premedicación con corticoides, paracetamol y/o antihistamínicos es controvertido. Objetivo: Evaluar si en pacientes con EII que utilizan IFX hay diferencias en las reacciones secundarias a infusión entre aquellos que utilizan o no premedicación. Métodos: Estudio descriptivo, observacional, retrospectivo en pacientes con EII, que han utilizado IFX entre enero 2009 y julio 2019. Se definieron como reacciones agudas aquellas ocurridas en las primeras 24 hrs.postinfusión y tardías después de ese período, clasificándose en leves, moderadas y severas. Se usó estadística descriptiva y de asociación (χ2; p < 0,05). Resultados: Se incluyeron 1.263 infusiones en un total de 64 pacientes, 52% hombres. Mediana de infusiones por paciente 22 (2-66). El 100% de las infusiones en inducción fueron con premedicación y en mantenimiento el 57%. La premedicación fue realizada con hidrocortisona, clorfenamina y paracetamol. La mayoría de las reacciones fueron agudas, de gravedad leve a moderada y ningún paciente necesitó descontinuar IFX. En mantenimiento hubo 9/718 (1,2%) reacciones a la infusión con premedicación y 4/358 (1,1%) sin ésta, sin diferencias significativas (p = 0,606). En inducción hubo 8/187 (4,3%) reacciones a la infusión, significativamente mayor al compararlas con ambos grupos de mantenimiento. Conclusión: En esta cohorte de pacientes, el no usar premedicación en fase de mantenimiento de IFX no aumentó el número de eventos adversos a este fármaco. Estos resultados sugieren que su indicación no sería necesaria.(AU)

Background: The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1-6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. Aim: The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. Methods: A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 hours postinfusion and late reactions for more than 24 hours. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p < 0.05). Results: Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2-66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. Conclusions: In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary.(AU)

Embarazo en enfermedad inflamatoria intestinal: experiencia en una cohorte chilena / Pregnancy in Inflammatory Bowel Disease: Experience of a Chilean cohort

Introducción: El diagnóstico de enfermedad inflamatoria intestinal (EII) se realiza, en un alto porcentaje, durante la edad reproductiva. La EII en remisión es el mejor escenario para planificar el embarazo. Objetivos: Describir las características clínicas del embarazo y del recién nacido, evaluando la actividad de la enfermedad en el momento de la concepción y en la evolución del embarazo en un centro terciario en Chile. Métodos: Estudio observacional, retrospectivo, incluyó a mujeres con EII que habían tenido un parto durante 2017-2020. Los datos demográficos, clínicos y obstétricos se obtuvieron del Registro de EII. Se realizó análisis estadístico descriptivo y de asociación (χ2, p ≤ 0,05). Resultados: Se incluyeron 60 mujeres en el estudio. Al inicio del embarazo, 21 (35%) presentaban actividad inflamatoria y 39 (65%) estaban en remisión. Del grupo con actividad, 16 (66%) permanecieron activas y seis tuvieron un aborto espontáneo. Aquellas en remisión, 26 (69%) permanecieron en esta condición; nueve pacientes (15%) habían suspendido el tratamiento, seis de las cuales presentaron actividad durante el embarazo. El consejo preconcepcional fue realizado en 23/60 pacientes, siendo mayor en el grupo que permaneció en remisión durante el embarazo (65% vs. 35%, p = 0,02). Pacientes con brotes durante el embarazo tuvieron mayor probabilidad de embarazo pretérmino (< 37 semanas) y recién nacido de menor peso comparado con el grupo que permaneció en remisión (89 vs. 74%; p = 0,161) y (2,885 vs. 3,370 g; p = 0,0014), respectivamente. Conclusión: La remisión durante el embarazo presenta los mejores resultados y el consejo preconcepcional permite un mejor control de la EII durante el embarazo.(AU)

Background: In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. Aims: To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile. Methods: We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05). Results: Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (<37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014). Conclusion: Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.(AU)

Pregnancy in Inflammatory Bowel Disease: Experience of a Chilean cohort. / Embarazo en enfermedad inflamatoria intestinal: experiencia en una cohorte chilena.

BACKGROUND: In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. AIMS: To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile. METHODS: We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05). RESULTS: Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (<37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014). CONCLUSION: Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.

¿Están recibiendo los pacientes con enfermedad inflamatoria intestinal una adecuada inmunización? / Are patients with inflammatory bowel disease receiving adequate immunisation?

Introducción: El tratamiento de la enfermedad inflamatoria intestinal (EII) puede aumentar el riesgo de infección. La inmunización es parte del manejo integral de la atención de estos pacientes. El objetivo de este estudio es describir la prescripción y adherencia a la vacunación en pacientes con EII e identificar los posibles factores asociados a esta. Métodos: Estudio analítico, descriptivo, transversal en pacientes de un Programa de EII de Chile, entre abril y junio de 2019. A los pacientes se les solicitó responder un cuestionario acerca de la adherencia a la vacunación. La información de las vacunas se obtuvo del Registro Nacional de Inmunizaciones. Se realizó análisis estadístico descriptivo y de asociación (χ2; p<0,05). Resultados: Se incluyeron 243 pacientes con EII (148 colitis ulcerosa [CU], 86 enfermedad de Crohn [EC] y 9 EII no clasificable). Solo 6 pacientes (2%) recibieron el esquema de inmunización completo. Las vacunas con los mayores porcentajes fueron contra la influenza (67%), virus hepatitis B (40%), neumocócica 13-valente (34%) y neumocócica 23-polisacárida (16%), siendo las dos primeras más frecuentes en EC vs. CU (p≤0,05). La administración de la vacuna contra la influenza ha aumentado significativamente, alcanzando un 67% el 2019. La encuesta mostró que el 23% no ha sido inmunizado con ninguna vacuna, principalmente por falta de tiempo, falta de prescripción médica y el alto costo económico. Conclusiones: En esta cohorte, aunque las tasas de vacunación son más altas que las reportadas previamente, la adherencia al programa de inmunización debe mejorar, siendo consideradas desde el diagnóstico por el equipo multidisciplinario.(AU)

Introduction: Inflammatory Bowel Disease (IBD) treatment may increase the risk of infections. Vaccines are part of the comprehensive IBD patient care. The aim of this study was to describe indications and adherence of immunizations in IBD and identify possible associated factors. Methods: A cross-sectional, analytic study was conducted in patients from an IBD Program of a tertiary center in Chile, between April – June 2019. Patients were asked to answer a vaccine survey and information also was obtained from the National Immunization Registry. Descriptive and association statistic were used (χ2; p<0.05). Results: A total of 243 patients were included (148 ulcerative colitis (UC), 86 Crohn's disease (CD) and 9 non-classifiable IBD). Only six patients (2%) of IBD patients received a complete immunization schedule. The highest vaccine rates were against influenza (67%), hepatitis B virus (40%), 13-valent pneumococcal (34%) and 23-polysaccharide pneumococcal (16%). The influenza vaccine rate has significantly increased, reaching 67% in 2019. The survey showed that 23% of patients have not been immunized with any vaccine, mainly due to lack of time, lack of medical prescription and high cost. Conclusions: In this cohort, although vaccination rates are higher than previously reported, adherence to IBD immunization program would be improved, being considered since diagnosis by the multidisciplinary team.(AU)

Infliximab in inflammatory bowel disease. Is premedication necessary? / Infliximab en enfermedad inflamatoria intestinal. ¿Es necesario premedicar?

BACKGROUND: The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1-6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. AIM: The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. METHODS: A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 hours postinfusion and late reactions for more than 24 hours. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p < 0.05). RESULTS: Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2-66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. CONCLUSIONS: In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary.

Are patients with inflammatory bowel disease receiving adequate immunisation? / ¿Están recibiendo los pacientes con enfermedad inflamatoria intestinal una adecuada inmunización?

INTRODUCTION: Inflammatory Bowel Disease (IBD) treatment may increase the risk of infections. Vaccines are part of the comprehensive IBD patient care. The aim of this study was to describe indications and adherence of immunizations in IBD and identify possible associated factors. METHODS: A cross-sectional, analytic study was conducted in patients from an IBD Program of a tertiary center in Chile, between April - June 2019. Patients were asked to answer a vaccine survey and information also was obtained from the National Immunization Registry. Descriptive and association statistic were used (χ2; p<0.05). RESULTS: A total of 243 patients were included (148 ulcerative colitis (UC), 86 Crohn's disease (CD) and 9 non-classifiable IBD). Only six patients (2%) of IBD patients received a complete immunization schedule. The highest vaccine rates were against influenza (67%), hepatitis B virus (40%), 13-valent pneumococcal (34%) and 23-polysaccharide pneumococcal (16%). The influenza vaccine rate has significantly increased, reaching 67% in 2019. The survey showed that 23% of patients have not been immunized with any vaccine, mainly due to lack of time, lack of medical prescription and high cost. CONCLUSIONS: In this cohort, although vaccination rates are higher than previously reported, adherence to IBD immunization program would be improved, being considered since diagnosis by the multidisciplinary team.

The Role of an Inflammatory Bowel Disease Nurse in the Follow-Up of Patients From a Latin American Inflammatory Bowel Disease Program.

Inflammatory bowel disease requires long-term treatment to maintain disease control. Favorable follow-up of patients indicates attention from a multidisciplinary team, in which the nurse's responsibilities have great importance. The aim of this observational, descriptive study was to describe the role of an inflammatory bowel disease nurse in the management of patients in a tertiary center in Chile, including all patients in follow-up between January 2016 and April 2017. Inflammatory bowel disease nurse contacts were recorded and classified. Demographic data, clinical variables, and patient satisfaction were also analyzed. A total of 597 patients (51%) were in follow-up over the 16-month period; 63% had ulcerative colitis, with a median age of 35 years. The inflammatory bowel disease nurse performed 760 contacts in 253 patients (42% of the follow-up patients). The most frequent nurse interventions were reinforcement of medical indications (42%), assessment of laboratory results (17%), and disease follow-up (12%); 49% related to education. Nurse interventions were focused in more severely ill patients; flares during the follow-up, biological therapy, immunomodulators, and steroids were all statistically significant. Of a sample of 107 patients surveyed, 96% perceived the inflammatory bowel disease program as excellent/good. The inflammatory bowel disease nurse plays an important role in the follow-up and management, specifically in education, of more severely ill patients.

[Environmental risk factors in the development and evolution of inflammatory bowel disease]. / Factores ambientales en el desarrollo y evolución de la enfermedad inflamatoria intestinal.

Environmental factors may influence the development of Inflammatory Bowel Disease and modify its natural history. The objective of this review is to evaluate current evidence about environmental factors associated with the disease. A better knowledge about the pathogenesis of the disease can lead to better treatment strategies and suggestions to prevent the disease.

Factores ambientales en el desarrollo y evolución de la enfermedad inflamatoria intestinal / Environmental risk factors in the development and evolution of inflammatory bowel disease

Environmental factors may influence the development of Inflammatory Bowel Disease and modify its natural history. The objective of this review is to evaluate current evidence about environmental factors associated with the disease. A better knowledge about the pathogenesis of the disease can lead to better treatment strategies and suggestions to prevent the disease.

Utilidad de la monitorización terapéutica de infliximab en el manejo de la enfermedad inflamatoria intestinal / Usefulness of therapeutic monitoring of infliximab in the treatment of inflammatory bowel disease

Background: Primary non-response and secondary loss of response (LOR) are significant problems of biological therapy for inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) in IBD patients receiving these drugs can improve outcomes. Aim: To measure serum infliximab levels and anti-infliximab antibodies (ATI) in patients with IBD post-induction phase and during maintenance therapy assessing the clinical course of IBD. Patients and Methods: Prospective study of IBD patients receiving infliximab between July 2016-May 2017. Group-A included patients who received induction therapy while Group-B included patients who were in maintenance therapy. TDM was performed in serum samples collected at weeks-14 and 30 in Group-A and before the infliximab maintenance dose in Group-B. Clinical scores, fecal calprotectin and endoscopic score were also evaluated. Results: Of 14 patients in Group-A, 57% achieved endoscopic response. Median serum infliximab concentrations at week-14 and 30 were 2.65 AU/mL (0.23-32.58) and 2.3 AU/mL (0.3-16.8), respectively. Patients with mucosal healing had non-significantly higher median infliximab concentrations at week- 14, as compared to week 30 (median 3.2 vs 2.2 AU/ml, respectively, p 0.6). ATI >10 ug/mL were found in one and seven patients at week-14 and 30, respectively. At 52 weeks of follow-up, four patients (31%) had LOR. Group-B included 36 patients, 33% had LOR. Median serum concentrations of infliximab were 1.4 AU/mL (0.27-7.03). No significant differences in serum infliximab concentration were observed between patients in remission and those with inflammatory activity. Seventeen patients had ATI >10 ug/mL. Conclusions: Clinical algorithms using TDM might help to optimize the pharmacological therapy of IBD.

Complementary and alternative medicine in patients with inflammatory bowel disease: A survey performed in a tertiary center in Chile.

OBJECTIVES: The aim of this study was to assess the type and prevalence of complementary and alternative medicine (CAM) use in patients with inflammatory bowel disease (IBD) who are treated at our center. DESIGN: Observational, cross-sectional questionnaire-based study that included patients from the IBD program of our center. SETTING: Tertiary clinical center in Santiago, Chile. MAIN OUTCOME MEASURES: Types of CAM being used by patients with IBD. RESULTS: A total of 200 patients were included, 68% ulcerative colitis, 29% Crohn's disease, and 3% non-classifiable IBD. Overall, 25% of the patients reported current use of CAM, 30% reported using in it the past, and 45% indicated that they had never used it before. The use of CAM was recommended in 20% of the patients by other healthcare professionals and in 10% of the patients by the gastroenterologist. Forty-nine percent of the patients informed the gastroenterologist that they were using CAM. Overall, 86% of the patients did not modify the conventional medical treatment (CMT). None of the patients who were using curcumin, homeopathic medicine, acupuncture or biomagnetism modified the CMT. CONCLUSIONS: The type of CAM being used plays an important role when the patient makes the decision to inform the gastroenterologist. Other healthcare professionals play an important role in providing the advice to start CAM. Gastroenterologists must be aware of the high prevalence of CAM use in IBD patients, actively ask about CAM use and guide the patients who want to use CAM in a responsible and safe manner.

[Acute severe ulcerative colitis treated with accelerated infliximab induction. Case report]. / Terapia de inducción acelerada con infliximab en paciente con colitis ulcerosa grave refractaria a corticoides. Caso clínico.

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition that requires early recognition, hospitalization and adequate treatment. Currently, the use of infliximab in ulcerative colitis (UC) is recommended in the case of severe disease refractory to corticosteroids, once that superimposed bacterial or viral infections (such as cytomegalovirus or Clostridium difficile) have been excluded. However, conventional weight-based regimens of infliximab might be insufficient for patients with ASUC. Accelerated infliximab induction regimen may increase its serum concentration levels and efficacy by reducing early colectomy rates in these patients. We report a 34 year old female presenting with an ASUC. She was initially treated with hydrocortisone 300 mg/day and mesalazine enemas 4 g/day with an unfavorable clinical response. At the fifth day of therapy, an accelerated induction therapy with infliximab was started in doses of 10 mg/kg at weeks 0, 1 and 4. After the second dose, there was a favorable response with reduction of abdominal pain, stool frequency and hematochezia. She was discharged with prednisone and azathioprine. After a year of starting infliximab, the patient remains in clinical remission.

Clinical, endoscopic and histological correlation and measures of association in ulcerative colitis.

OBJECTIVE: To determine the correlation between clinical, fecal, endoscopic and histological activity in patients with ulcerative colitis (UC). METHODS: A correlational cross-sectional analysis was performed in patients with UC who underwent colonoscopy between February and December 2016. Clinical, endoscopic, fecal and histological activities were determined using the partial Mayo subscore, Mayo endoscopic subscore and modified Mayo endoscopic subscore, fecal calprotectin and Geboes score and the presence of basal plasmacytosis, respectively. Scores were analyzed using Spearman's rank correlation test. To determine the association between scores and some clinical variables and active UC, univariate and multivariate logistic regressions were used. RESULTS: Altogether 105 procedures (93 patients) were included. In 64.8% of the procedures, the mucosa was inflamed; however, 14.7% did not show histological inflammation. Endoscopic remission was observed in the other 35.2% of procedures; however, in biopsies 21.6% exhibited histological inflammation. Mayo endoscopic subscore and modified Mayo endoscopic score were well correlated but were only moderately correlated with clinical and histological scores. Furthermore, there was a moderate correlation between Mayo endoscopic score and Geboes score. Conversely, histological scores were poorly correlated with partial Mayo score. In multivariate analysis, Geboes score and basal plasmacytosis were predictive of active disease (OR 3.505, 95% CI 1.544-7.959 and OR 3.240, 95% CI 1.123-9.349, respectively), whereas biological therapy was found to be protective against UC (OR 0.021, 95% CI 0.000-0.641). CONCLUSION: Clinical, endoscopic and histological activities were moderately correlated, while Geboes score and basal plasmacytosis were predictive of endoscopically active UC.

Terapia de inducción acelerada con infliximab en paciente con colitis ulcerosa grave refractaria a corticoides: caso clínico / Acute severe ulcerative colitis treated with accelerated infliximab induction: case report

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition that requires early recognition, hospitalization and adequate treatment. Currently, the use of infliximab in ulcerative colitis (UC) is recommended in the case of severe disease refractory to corticosteroids, once that superimposed bacterial or viral infections (such as cytomegalovirus or Clostridium difficile) have been excluded. However, conventional weight-based regimens of infliximab might be insufficient for patients with ASUC. Accelerated infliximab induction regimen may increase its serum concentration levels and efficacy by reducing early colectomy rates in these patients. We report a 34 year old female presenting with an ASUC. She was initially treated with hydrocortisone 300 mg/day and mesalazine enemas 4 g/day with an unfavorable clinical response. At the fifth day of therapy, an accelerated induction therapy with infliximab was started in doses of 10 mg/kg at weeks 0, 1 and 4. After the second dose, there was a favorable response with reduction of abdominal pain, stool frequency and hematochezia. She was discharged with prednisone and azathioprine. After a year of starting infliximab, the patient remains in clinical remission.

[Natalizumab for the treatment of Crohn’s disease: Report of three cases]. / Experiencia local con natalizumab en pacientes con enfermedad de Crohn refractaria a anti-TNF: Casos clínicos.

Anti-tumor necrosis factor-α (TNF) agents have dramatically changed the management of Crohn’s Disease (CD). However, a significant number of these patients do not respond at all or cease to respond to antibodies against TNF. In this clinical situation, the options include intensification of anti-TNF therapy by either increasing the dose or by shortening the administration interval, the use of a second anti-TNF or medications with a different mechanism of action. Among the later, Natalizumab, a humanized IgG4 monoclonal antibody against α4ß1 and α4ß7 integrins, is safe and effective in inducing and maintaining remission in active CD patient’s refractory to anti-TNF. In spite of this, Natalizumab use has been limited because of an increased risk of progressive multifocal leukoencephalophaty which results from reactivation of the John Cunningham (JC) virus. However, the presence of antibodies against JC virus in serum can be used to reduce the risk for this complication. We report three patients with Crohn’s disease refractory to treatment with infliximab, who responded successfully to the use of Natalizumab.