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Crohn Disease: HELP
Articles by Iván Guerra
Based on 15 articles published since 2009
(Why 15 articles?)
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Between 2009 and 2019, I. Guerra wrote the following 15 articles about Crohn Disease.
 
+ Citations + Abstracts
1 Guideline Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the use of thiopurines in inflammatory bowel disease. 2018

Bermejo, Fernando / Aguas, Mariam / Chaparro, María / Domènech, Eugeni / Echarri, Ana / García-Planella, Esther / Guerra, Iván / Gisbert, Javier P / López-Sanromán, Antonio / Anonymous1510934. ·Servicio de Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España. Electronic address: fbermejos1@gmail.com. · Servicio de Digestivo, Hospital Universitari La Fe, Valencia, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España. · Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicios de Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, España. · Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicio de Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, España. · Servicio de Digestivo, Complejo Hospitalario Universitario de Ferrol, Ferrol, España. · Servicio de Digestivo, Hospital Universitari Santa Creu i Sant Pau, Barcelona, España. · Servicio de Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España. · Servicio de Digestivo, Hospital Universitario Ramón y Cajal, Madrid, España. ·Gastroenterol Hepatol · Pubmed #29357999.

ABSTRACT: Thiopurines (azathioprine and mercaptopurine) are widely used in patients with inflammatory bowel disease. In this paper, we review the main indications for their use, as well as practical aspects on efficacy, safety and method of administration. They are mainly used to maintain remission in steroid-dependent disease or with ciclosporin to control a severe ulcerative colitis flare-up, as well as to prevent postoperative Crohn's disease recurrence, and also in combination therapy with biologics. About 30-40% of patients will not respond to treatment and 10-20% will not tolerate it due to adverse effects. Before they are prescribed, immunisation status against certain infections should be checked. Determination of thiopurine methyltransferase activity (TPMT) is not mandatory but it increases initial safety. The appropriate dose is 2.5mg/kg/day for azathioprine and 1.5mg/kg/day for mercaptopurine. Some adverse effects are idiosyncratic (digestive intolerance, pancreatitis, fever, arthromyalgia, rash and some forms of hepatotoxicity). Others are dose-dependent (myelotoxicity and other types of hepatotoxicity), and their surveillance should never be interrupted during treatment. If therapy fails or adverse effects develop, management can include switching from one thiopurine to the other, reducing the dose, combining low doses of azathioprine with allopurinol and assessing metabolites, before their use is ruled out. Non-melanoma skin cancer, lymphomas and urinary tract tumours have been linked to thiopurine therapy. Thiopurine use is safe during conception, pregnancy and breastfeeding.

2 Review Pharmacological Approach to the Management of Crohn's Disease Patients with Perianal Disease. 2018

Bermejo, Fernando / Guerra, Iván / Algaba, Alicia / López-Sanromán, Antonio. ·Department of Gastroenterology, University Hospital of Fuenlabrada, Madrid, Spain. fbermejos1@gmail.com. · Department of Medicine and Surgery, Universidad Rey Juan Carlos, Madrid, Spain. fbermejos1@gmail.com. · Department of Gastroenterology, University Hospital of Fuenlabrada, Madrid, Spain. · Department of Gastroenterology and Hepatology, University Hospital Ramón y Cajal, Madrid, Spain. ·Drugs · Pubmed #29139091.

ABSTRACT: Perianal localization of Crohn's disease involves significant morbidity, affects quality of life and results in an increased use of healthcare resources. Medical and surgical therapies contribute to its management. The objective of this review is to address the current understanding in the management of perianal Crohn's disease, with the main focus in reviewing pharmacological therapies, including stem cells. In complex fistulas, once local sepsis has been controlled by surgical drainage and/or antibiotics, anti-TNF drugs (infliximab, adalimumab) are the first-line therapy, with or without associated immunomodulators. Combining surgery and anti-TNF therapy has additional benefits for healing. However, response is inadequate in up to half of cases. A possible role of new biological drugs in this context (vedolizumab, ustekinumab) is an area of ongoing investigation, as is the local application of autologous or allogeneic mesenchymal stem cells. These are non-hematopoietic multipotent cells with anti-inflammatory and immunomodulatory properties, the use of which may successfully treat refractory patients, and seem to be a promising and safe alternative to achieving fistula healing in Crohn's disease, without known systemic effects.

3 Article Correlation Between Anti-TNF Serum Levels and Endoscopic Inflammation in Inflammatory Bowel Disease Patients. 2019

Chaparro, María / Barreiro-de Acosta, Manuel / Echarri, Ana / Almendros, Rosendo / Barrio, Jesús / Llao, Jordina / Gomollón, Fernando / Vera, Maribel / Cabriada, José Luis / Guardiola, Jordi / Guerra, Iván / Beltrán, Belén / Roncero, Oscar / Busquets, David / Taxonera, Carlos / Calvet, Xavier / Ferreiro-Iglesias, Rocío / Ollero Pena, Virginia / Bernardo, David / Donday, María G / Garre, Ana / Godino, Ana / Díaz, Ana / Gisbert, Javier P. ·Servicio de Aparato Digestivo, Hospital Universitario de La Princesa e Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain. mariachs2005@gmail.com. · Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. mariachs2005@gmail.com. · Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain. · Servicio de Aparato Digestivo, Complejo Hospitalario Universitario de Ferrol, Coruña, Spain. · Servicio de Farmacia, Hospital Universitario Rio Hortega, Valladolid, Spain. · Servicio de Aparato Digestivo, Hospital Universitario Rio Hortega, Valladolid, Spain. · Servicio de Aparato Digestivo, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. · Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa and IIS-Aragón, Saragossa, Spain. · Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. · Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Majadahonda, Spain. · Servicio de Aparato Digestivo, Hospital Galdakao-Usansolo, Vizcaya, Spain. · Servicio de Aparato Digestivo, Hospital Universitari de Bellvitge-IDIBELL, Universidad de Barcelona, Barcelona, Spain. · Servicio de Aparato Digestivo, Hospital Universitario de Fuenlabrada, Madrid, Spain. · Servicio de Aparato Digestivo, Hospital Universitari La Fe, Valencia, Spain. · Servicio de Aparato Digestivo, Complejo Hospitalario la Mancha Centro, Ciudad Real, Spain. · Servicio de Aparato Digestivo, Hospital Universitari de Girona Doctor Josep Trueta, Girona, Spain. · Servicio de Aparato Digestivo, Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. · Servicio de Aparato Digestivo, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain. · Servicio de Aparato Digestivo, Hospital Universitario de La Princesa e Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain. · Servicio de Análisis Clínicos, Hospital Universitario de La Princesa e Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain. ·Dig Dis Sci · Pubmed #30426297.

ABSTRACT: OBJECTIVES: (a) To evaluate the diagnostic accuracy of anti-TNF trough levels to predict mucosal healing in inflammatory bowel disease (IBD); (b) to determine the best cut-off point to predict mucosal healing in IBD patients treated with anti-TNF. METHODS: This is a multicenter, prospective study. IBD patients under anti-TNF treatment for at least 6 months that had to undergo an endoscopy were included. Mucosal healing was defined as: Simple endoscopic score for Crohn's Disease < 3 for Crohn's disease (CD), Rutgeerts score < i2 for CD in postoperative setting, or Mayo endoscopic score ≤ 1 for ulcerative colitis (UC). Anti-TNF concentrations were measured using SMART ELISAs at trough. RESULTS: A total of 182 patients were included. Anti-TNF trough levels were significantly higher among patients that had mucosal healing than among those who did not. The area under the curve of infliximab for mucosal healing was 0.63 (best cutoff value 3.4 μg/mL), and for adalimumab 0.60 (best cutoff value 7.2 μg/mL). In the multivariate analysis, having anti-TNF drug levels above the cutoff values [odds ratio (OR) 3.1]) and having UC instead of CD (OR 4) were associated with a higher probability of having mucosal healing. Additionally, the need for an escalated dosage (OR 0.2) and current smoking habit (OR 0.2) were also associated with a lower probability of mucosal healing. CONCLUSIONS: There was an association between anti-TNF trough levels and mucosal healing in IBD patients; however, the accuracy of the determination of infliximab and adalimumab concentrations able to predict mucosal healing was suboptimal.

4 Article Resources used in the treatment of perianal Crohn's disease and the results in a real-life cohort. 2018

Rubín de Célix Vargas, Cristina / Algaba, Alicia / Guerra, Iván / Serrano, Ángel / Pérez-Viejo, Estíbaliz / Aulló, Carolina / Bermejo, Fernando. ·Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Madrid, España. Electronic address: cristina.rubindecelix@salud.madrid.org. · Servicio de Aparato Digestivo, Hospital Universitario de Fuenlabrada, Madrid, España. · Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Fuenlabrada, Madrid, España. · Servicio de Radiodiagnóstico, Hospital Universitario de Fuenlabrada, Madrid, España. ·Gastroenterol Hepatol · Pubmed #29759924.

ABSTRACT: OBJECTIVE: To study the multidisciplinary management of patients with Crohn's disease (CD) and perianal disease (perianal Crohn's disease, PCD), as well as to analyse a possible relationship between the recurrence of perianal symptoms, the type of fistula and the treatment used. PATIENTS AND METHODS: Descriptive, retrospective study of patients with PCD who were treated in the Inflammatory Bowel Disease Unit. Epidemiological, clinical, diagnostic and therapeutic variables were collected, as well as clinical outcome and response to treatment. RESULTS: Of the 300 patients who attended the outpatient clinic at a university hospital, 65 had PCD. Sixteen simple fistulas (24.6%) and 49 complex fistulas (75.4%) were diagnosed. The most commonly used diagnostic technique was the endoanal ultrasound (45%). Antibiotics were used in 77.4% of patients, and 70% needed anti-TNF therapy to manage the PCD. Surgery was performed on 75.4% of the patients overall. PCD recurred in 41.5% of cases, requiring a change of the biological drugs administered and/or surgery. Complex fistulas were more likely to require surgery (P=.012) and recurrence of PCD was also more common with complex fistulas (P=.036). CONCLUSION: Management of PCD must be multidisciplinary and combined. Most patients with complex PCD require treatment based on biological drugs. Despite therapy, remission of perianal symptoms is not achieved in a percentage of patients, supporting the need to develop new therapies for refractory cases.

5 Article Ratio of Circulating Estrogen Receptors Beta and Alpha (ERβ/ERα) Indicates Endoscopic Activity in Patients with Crohn's Disease. 2017

Linares, Pablo M / Algaba, Alicia / Urzainqui, Ana / Guijarro-Rojas, Mercedes / González-Tajuelo, Rafael / Garrido, Jesús / Chaparro, María / Gisbert, Javier P / Bermejo, Fernando / Guerra, Iván / Castellano, Víctor / Fernández-Contreras, María-Encarnación. ·Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), C/ Diego de León 62, 28006, Madrid, Spain. · Department of Gastroenterology, Hospital Universitario de Fuenlabrada, C/ Camino del Molino 2, 28942, Fuenlabrada-Madrid, Spain. · Department of Immunology, Hospital Universitario de la Princesa, IIS-IP, C/ Diego de León 62, 28006, Madrid, Spain. · Department of Pathology, Hospital Universitario de la Princesa, IIS-IP, C/ Diego de León 62, 28006, Madrid, Spain. · Department of Social Psychology and Methodology, School of Psychology, Universidad Autónoma de Madrid (UAM), C/ Ivan Pavlov 6. Ciudad Universitaria de Cantoblanco, 28049, Madrid, Spain. · Department of Pathology, Hospital Universitario de Fuenlabrada, C/ Camino del Molino 2, 28942, Fuenlabrada-Madrid, Spain. · Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), C/ Diego de León 62, 28006, Madrid, Spain. mefdezcontreras@hotmail.com. · Departments of Anatomy I and Immunology, School of Medicine, Universidad Alfonso X El Sabio (UAX), Avda. de la Universidad 1, 28691, Villanueva de la Cañada, Madrid, Spain. mefdezcontreras@hotmail.com. ·Dig Dis Sci · Pubmed #28823012.

ABSTRACT: BACKGROUND: Data supporting a role of female hormones and/or their receptors in inflammatory bowel disease (IBD) are increasing, but most of them are derived from animal models. Estrogen receptors alpha (ERα) and beta (ERβ) participate in immune and inflammatory response, among a variety of biological processes. Their effects are antagonistic, and the net action of estrogens may depend on their relative proportions. AIM: To determine the possible association between the balance of circulating ERβ and ERα (ERβ/ERα) and IBD risk and activity. METHODS: Serum samples from 145 patients with IBD (79 Crohn's disease [CD] and 66 ulcerative colitis [UC]) and 39 controls were retrospectively studied. Circulating ERα and ERβ were measured by ELISA. Disease activities were assessed by clinical and endoscopic indices specific for CD and UC. RESULTS: Low values of ERβ/ERα ratio were directly associated with clinical (p = 0.019) and endoscopic (p = 0.002) disease activity. Further analyses by type of IBD confirmed a strong association between low ERβ/ERα ratio and CD clinical (p = 0.011) and endoscopic activity (p = 0.002). The receiver operating curve (ROC) analysis showed that an ERβ/ERα ratio under 0.85 was a good marker of CD endoscopic activity (area under the curve [AUC]: 0.84; p = 0.002; sensitivity: 70%; specificity: 91%). ERβ/ERα ratio was not useful to predict UC activity. CONCLUSIONS: An ERβ/ERα ratio under 0.85 indicated CD endoscopic activity. The determination of serum ERβ/ERα might be a useful noninvasive screening tool for CD endoscopic activity.

6 Article Mercaptopurine and inflammatory bowel disease: the other thiopurine. 2017

Bermejo San José, Fernando / Algaba, Alicia / López Durán, Sergio / Guerra, Iván / Aicart, Marta / Hernández-Tejero, María / Garrido, Elena / de Lucas, María / Bonillo, Daniel / López Sanromán, Antonio. ·Servicio de Digestivo, Hospital Universitario de Fuenlabrada, España. · Digestivo, Hospital Universitario de Fuenlabrada. · Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, España. · Gastroenterologia, Hospital Universitario Ramón y Cajal. · Gastroenterología, Hospital Universitario Ramón y Cajal. · Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal. Madrid, ESPAÑA. ·Rev Esp Enferm Dig · Pubmed #27809554.

ABSTRACT: BACKGROUND: Data about use and effectiveness of mercaptopurine in inflammatory bowel disease are relatively limited. AIMS: To assess the possible therapeutic indications, efficacy and safety of mercaptopurine as an alternative to azathioprine in inflammatory bowel disease. METHODS: Retrospective observational study in patients treated with mercaptopurine in a total cohort of 1,574 patients with inflammatory bowel disease. RESULTS: One hundred and fifty-two patients received mercaptopurine, 15.7% of these patients as an initial thiopurine, 5.3% after azathioprine failure, and 79% after azathioprine intolerance. In 52.6% of patients (n = 80), adverse effects of mercaptopurine occurred, resulting in withdrawal in 49 of them. Mercaptopurine was effective in 39% of cases (95% CI 31-48%). In the remaining patients, failure was due mainly to withdrawal due to side effects (55.1%) and therapeutic step-up (33.7%). The average total time of mercaptopurine exposure was 36 months (IQR: 2-60). Myelotoxicity with mercaptopurine was more common in patients with intermediate TPMT activity than in those with normal activity (p = 0.046). CONCLUSIONS: In our setting, mercaptopurine is primarily used as a rescue therapy in patients with azathioprine adverse effects. This could explain its modest efficacy and the high rate of adverse effects. However, this drug is still an alternative in this group of patients, before a therapeutic step-up to biologics is considered.

7 Article Standardization of the homogeneous mobility shift assay protocol for evaluation of anti-infliximab antibodies. Application of the method to Crohn's disease patients treated with infliximab. 2016

Hernández-Breijo, B / Chaparro, M / Cano-Martínez, D / Guerra, I / Iborra, M / Cabriada, J L / Bujanda, L / Taxonera, C / García-Sánchez, V / Marín-Jiménez, I / Barreiro-de Acosta, M / Vera, I / Martín-Arranz, M D / Mesonero, F / Sempere, L / Gomollón, F / Hinojosa, J / Gisbert, J P / Guijarro, L G / Anonymous12560882. ·Systems Biology Department, Universidad de Alcalá and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Alcalá de Henares, Spain. · Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and CIBEREHD, Madrid, Spain. · Hospital de Fuenlabrada, Madrid, Spain. · Hospital la Fe, Valencia and CIBEREHD, Spain. · Hospital de Galdakano, Vizcaya, Spain. · Hospital de Donostia, Guipúzcoa, Instituto Biodonostia, UPV/EHU and CIBEREHD, Spain. · Hospital Clínico San Carlos, and IdISSC, Madrid, Spain. · Hospital Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba, Universidad de Córdoba, Córdoba, Spain. · Hospital Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. · Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain. · Hospital Universitario Puerta de Hierro, Madrid, Spain. · Hospital Universitario la Paz, Madrid, Spain. · Hospital Universitario Ramón y Cajal, Madrid, Spain. · Hospital General de Alicante, Alicante, Spain. · Hospital Clínico Universitario "Lozano Blesa", IIS Aragón, Zaragoza and CIBEREHD, Spain. · Hospital de Manises, Valencia, Spain. · Systems Biology Department, Universidad de Alcalá and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Alcalá de Henares, Spain. Electronic address: luis.gonzalez@uah.es. ·Biochem Pharmacol · Pubmed #27664854.

ABSTRACT: BACKGROUND: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. METHODS: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. RESULTS: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10nM) during the observation period (54weeks). Serum concentration of ATI higher than 10nM dramatically increased the probability (OR=51.1; 95% CI: 20.4-128.0; p<0.0001) of presenting low levels of IFX (⩽1.5nM) in serum, as observed in some CD patients treated with standard doses of the drug. CONCLUSIONS: The HMSA-method described here allows an accurate quantification of ATI concentration in international units (IU) and therefore it could be useful in the study of the relationship between ATI concentration, infliximab level and the clinical response to the drug.

8 Article Incidence, Clinical Characteristics, and Management of Psoriasis Induced by Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: A Nationwide Cohort Study. 2016

Guerra, Iván / Pérez-Jeldres, Tamara / Iborra, Marisa / Algaba, Alicia / Monfort, David / Calvet, Xavier / Chaparro, María / Mañosa, Miriam / Hinojosa, Esther / Minguez, Miguel / Ortiz de Zarate, Jone / Márquez, Lucía / Prieto, Vanessa / García-Sánchez, Valle / Guardiola, Jordi / Rodriguez, G Esther / Martín-Arranz, María Dolores / García-Tercero, Iván / Sicilia, Beatriz / Masedo, Ángeles / Lorente, Rufo / Rivero, Montserrat / Fernández-Salazar, Luis / Gutiérrez, Ana / Van Domselaar, Manuel / López-SanRomán, Antonio / Ber, Yolanda / García-Sepulcre, Marifé / Ramos, Laura / Bermejo, Fernando / Gisbert, Javier P / Anonymous1770860. ·1Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Madrid, Spain; 2Department of Gastroenterology, Hospital Clinic, Barcelona, Spain; 3Department of Gastroenterology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD); 4Department of Gastroenterology, Hospital Universitario La Fe, Valencia, Spain; 5Department of Gastroenterology, Consorci Sanitari de Terrassa, Barcelona, Spain; 6Department of Gastroenterology, Corporació Sanitaria Parc Taulí, Sabadell, Spain; 7Department of Gastroenterology, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain; 8Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 9Department of Gastroenterology, Hospital de Manises, Valencia, Spain; 10Department of Gastroenterology, Hospital Clínico de Valencia, Universitat de València, Valencia, Spain; 11Department of Gastroenterology, Hospital de Basurto, Bilbao, Spain; 12Department of Gastroenterology, Hospital del Mar, Barcelona, Spain; 13Department of Gastroenterology, Hospital Universitario de Salamanca, Salamanca, Spain; 14Department of Gastroenterology, Hospital Reina Sofía, IMIBIC, Universidad de Córdoba, Córdoba, Spain; 15Department of Gastroenterology, Hospital Universitari de Bellvitge-IDIBELL, Barcelona, Spain; 16Department of Gastroenterology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain; 17Department of Gastroenterology, Hospital Universitario La Paz, Madrid, Spain; 18Department of Gastroenterology, Hospital Universitario Santa Lucía, Cartagena, Spain; 19Department of Gastroenterology, Hospital Universitario de Burgos, Burgos, Spain; 20Department of Gastroenterology, Hospital Universitario 12 de Octubre, Madrid, Spain; 21Department of Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain; 22Department of Gastroenterology, Hospital Universitario Marqué ·Inflamm Bowel Dis · Pubmed #26933750.

ABSTRACT: BACKGROUND: Psoriasis induced by anti-tumor necrosis factor-α (TNF) therapy has been described as a paradoxical side effect. AIM: To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. METHODS: Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. RESULTS: Anti-TNF-induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4-2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4-0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3-2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel disease, Montreal Classification, and first anti-TNF drug used were not associated with the risk of psoriasis. Topical steroids were the most frequent treatment (70%), achieving clinical response in 78% of patients. Patients switching to another anti-TNF agent resulted in 60% presenting recurrence of psoriasis. In 45 patients (37%), the anti-TNF therapy had to be definitely withdrawn. CONCLUSIONS: The incidence rate of psoriasis induced by anti-TNF therapy is higher in women and in smokers/former smokers. In most patients, skin lesions were controlled with topical steroids. More than half of patients switching to another anti-TNF agent had recurrence of psoriasis. In most patients, the anti-TNF therapy could be maintained.

9 Article The effects of infliximab or adalimumab on vascular endothelial growth factor and angiopoietin 1 angiogenic factor levels in inflammatory bowel disease: serial observations in 37 patients. 2014

Algaba, Alicia / Linares, Pablo M / Encarnación Fernández-Contreras, M / Figuerola, Ariadna / Calvet, Xavier / Guerra, Iván / de Pousa, Inés / Chaparro, María / Gisbert, Javier P / Bermejo, Fernando. ·*Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Madrid, Spain; †Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain; ‡Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain; §Gastroenterology Unit, Hospital de Sabadell, Institut Parc Taulí, Sabadell, Barcelona, Spain; and ‖Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. ·Inflamm Bowel Dis · Pubmed #24562175.

ABSTRACT: BACKGROUND: Infliximab and adalimumab effectiveness might be related with changes in angiogenic factors. The aim of the study was to compare the concentrations of angiogenic proteins in patients with inflammatory bowel disease (IBD) and healthy controls and to analyze changes in the levels during infliximab and adalimumab treatment. METHODS: A prospective case-control study was conducted in 37 patients with IBD starting treatment with infliximab (16 with Crohn's disease and 6 with ulcerative colitis) or adalimumab (15 with Crohn's disease) and 40 control subjects. Four samples were taken from IBD patients, one before each of the first 3 doses of infliximab/adalimumab and one at week 14. Serum levels of vascular endothelial growth factor (VEGF), placental growth factor, angiopoietin 1 (Ang1), angiopoietin 2, and Tie2 were measured using enzyme-linked immunosorbent assay. RESULTS: Patients with IBD had higher VEGF levels than control subjects (511.5 ± 255.6 versus 395.5 ± 256.4; P = 0.05). Patients who achieved remission at the third dose of anti-TNF-alpha had lower VEGF levels at baseline (453.5 ± 250.7 versus 667.5 ± 153.9 pg/mL) and before the second (409.7 ± 217 versus 681.3 ± 350.6 pg/mL) and third (400.5 ± 222.8 versus 630.4 ± 243.1 pg/mL) doses compared with those with no remission (P < 0.05). Ang1 levels decreased before each treatment dose in patients who achieved remission (P < 0.05). High baseline VEGF levels predicted for a poor response to anti-TNF-alpha therapy (area under the receiver operating characteristics curve = 0.8), whereas high Ang1 levels were associated with disease remission (area under the receiver operating characteristics curve = 0.7). Concentrations of angiogenic proteins did not correlate with clinical activity scores. CONCLUSIONS: Circulating VEGF and Ang1 levels decrease after anti-TNF-alpha therapy and may predict response to treatment. Whether these changes are a direct effect of anti-TNF-alpha therapy or a sign of disease improvement remains to be elucidated.

10 Article Response to letter: folate deficiency in Crohn's disease. 2014

Bermejo, Fernando / Algaba, Alicia / Guerra, Iván / Gisbert, Javier P. ·Gastroenterology Units, Hospital Universitario de Fuenlabrada , Madrid , Spain. ·Scand J Gastroenterol · Pubmed #24328943.

ABSTRACT: Folate deficiency in patients with Crohn's disease may be due to a combination of factors: poor diet, malabsorption, increased requirements due to inflammation of the mucosa, and the taking of certain drugs as sulfasalazine and methotrexate. A significant proportion of patients with Crohn's disease suffer from folate deficiency, suggesting that regular screening should be performed.

11 Article Should we monitor vitamin B12 and folate levels in Crohn's disease patients? 2013

Bermejo, Fernando / Algaba, Alicia / Guerra, Iván / Chaparro, María / De-La-Poza, Gema / Valer, Paz / Piqueras, Belén / Bermejo, Andrea / García-Alonso, Javier / Pérez, María-José / Gisbert, Javier P. ·Department of Gastroenterology, Hospital Universitario de Fuenlabrada , Madrid , Spain. ·Scand J Gastroenterol · Pubmed #24063425.

ABSTRACT: OBJECTIVE: Crohn's disease commonly involves the small intestine, which is the site of vitamin B12 and folate absorption. Our aim was to define the prevalence of vitamin B12 and folate deficiency in patients with Crohn's disease and to identify predictive factors associated with such abnormalities. METHODS: Two years prospective study of 180 consecutive Crohn's disease patients. Vitamin B12 and folate deficiency was defined as serum levels below 200 pg/ml and 3 ng/ml, respectively. We analysed prevalence of these deficiencies and possible predictive factors including small intestine resection, disease location, activity and duration of disease. Controls were ulcerative colitis patients (n = 70). RESULTS: The prevalence of B12 deficiency in Crohn's disease was 15.6% (95%CI 9.7-20%) compared with 2.8% (95%CI 0.8-9.8%) in ulcerative colitis (p = 0.007). With regard to folate deficiency, the prevalence in patients with Crohn's disease was 22.2% (95%CI 16-28%) compared with 4.3% (95%CI 1.4-12%) in ulcerative colitis (p = 0.001); 7.8% of Crohn's disease patients had macrocytic anemia. Ileal resection was found to be a risk factor for B12 deficiency (OR 2.7; 1.2-6.7; p = 0.02), and disease activity a risk factor for folate deficiency (OR 2.4; 1.2-5.1; p = 0.01). CONCLUSION: A significant proportion of patients with Crohn's disease suffer from vitamin B12 and/or folate deficiency, suggesting that regular screening should be performed, with closer monitoring in patients with ileal resection or active disease.

12 Article Relationship between levels of angiogenic and lymphangiogenic factors and the endoscopic, histological and clinical activity, and acute-phase reactants in patients with inflammatory bowel disease. 2013

Algaba, Alicia / Linares, Pablo M / Fernández-Contreras, M Encarnación / Ordoñez, Amparo / Trápaga, Javier / Guerra, Iván / Chaparro, María / de la Poza, Gema / Gisbert, Javier P / Bermejo, Fernando. ·Department of Gastroenterology of the Hospital Universitario de Fuenlabrada, Madrid, Spain. Electronic address: alicia_algaba@hotmail.com. ·J Crohns Colitis · Pubmed #23642997.

ABSTRACT: BACKGROUND: Angiogenic and lymphangiogenic factors (ALFs) may play an important role in inflammatory bowel disease (IBD). Our aims were to evaluate levels of ALFs in serum and the colonic mucosa culture supernatant (MCS) of patients with active and quiescent IBD and healthy subjects and to correlate them with the endoscopic, clinical and histological activity and with acute-phase reactants. METHODS: This is a prospective study of 28 controls and 72 IBD patients. Serum and MCS concentration of VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, PlGF, Ang1, Ang2 and Tie2 were measured by ELISA. Activity was established by specific indexes (CDAI, Mayo score, SES-CD, D'Haens scale and Riley index). Acute-phase reactants were routinely measured. RESULTS: MCS levels of all ALFs except VEGFR3 were higher in patients with endoscopic (p<0.05), clinical (p<0.05) and histological (p<0.01) activity than in those without it. In serum, VEGFA, VEGFC and Ang1 and VEGFA and Ang1 levels were lower in patients in remission than in patients with clinical and histological activity, respectively (p<0.05). There was a correlation between serum and MCS concentrations for VEGFD, VEGFR3, PlGF and Tie2 (r=0.25, r=0.48, r=-0.45 and r=0.36; p<0.05). Ang2 in MCS was the best predictor for the diagnosis of endoscopic, histological and clinical activity (area under ROC curve>0.8). CONCLUSIONS: MCS determination suggests a local increase in ALFs that correlates with IBD activity. Although the correlation between ALFs in serum and MCS was not good, the study of some of these factors as possible targets of new drugs for IBD constitutes a key new line of research.

13 Article Efficacy of different therapeutic options for spontaneous abdominal abscesses in Crohn's disease: are antibiotics enough? 2012

Bermejo, Fernando / Garrido, Elena / Chaparro, María / Gordillo, Jordi / Mañosa, Miriam / Algaba, Alicia / López-Sanromán, Antonio / Gisbert, Javier P / García-Planella, Esther / Guerra, Iván / Domènech, Eugeni. ·Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain. fbermejos@medynet.com ·Inflamm Bowel Dis · Pubmed #22674826.

ABSTRACT: BACKGROUND: Management of abdominal abscesses (AA) in Crohn's disease (CD) always includes antibiotics, and some type of drainage is added according to the response and other considerations. Our aim was to assess the efficacy of different therapeutic approaches to spontaneous AA in CD. METHODS: All cases of AA in CD were identified from the databases of five university hospitals. Postoperative cases were excluded. Therapeutic success was defined as abscess resolution and nonreappearance within 1 year of follow-up. RESULTS: We identified 128 cases in 2236 patients (cumulative incidence 5.7%). Initial therapy included medical therapy with antibiotics alone (42.2%), antibiotics plus percutaneous drainage (23.4%), and antibiotics plus surgical drainage (34.4%). The highest final efficacy corresponded to surgery (91%) as compared with antibiotic therapy alone (63%) or percutaneous drainage (30%). Failure of initial therapy was predicted by immunomodulators at diagnosis (odds ratio [OR] 8.45; 95% confidence interval [CI] 1.16-61.5; P = 0.03), fistula detectable in imaging techniques (OR 5.43; 95% CI 1.18-24.8; P = 0.02), and abscess size (OR 1.65; 95% CI 1.07-2.54; P = 0.02) only for patients treated with antibiotic therapy alone. Percutaneous drainage was associated with 19% of complications (enterocutaneous fistulas 13%); surgery was associated with 13% of postoperative complications (enterocutaneous fistulas 7.7%). Following abscess resolution, 60% of patients were started on thiopurines, 9% on biologics, and in 31% baseline therapy was not modified. CONCLUSIONS: Management of spontaneous AA in CD with antibiotics alone seems to be a good option for small abscesses, especially those without associated fistula and appearing in immunomodulator-naïve patients. Surgery offers better results in the remaining clinical settings, although percutaneous drainage can avoid operative treatment in some cases.

14 Article Factors that modify therapy adherence in patients with inflammatory bowel disease. 2010

Bermejo, Fernando / López-San Román, Antonio / Algaba, Alicia / Guerra, Iván / Valer, Paz / García-Garzón, Silvia / Piqueras, Belén / Villa, Carlos / Bermejo, Andrea / Rodríguez-Agulló, José L. ·Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain. fbermejos@medynet.com ·J Crohns Colitis · Pubmed #21122538.

ABSTRACT: OBJECTIVES: Inflammatory bowel disease is associated with a high risk of deficient adherence to therapy. Our study was designed to analyze the adherence to treatment in a specialized inflammatory bowel disease clinic, and to study which factors could influence it. METHODS: 107 consecutive patients (64% Crohn's disease, 36% ulcerative colitis) filled up an anonymous survey with data on demography, disease, therapy and a self-applied adherence declaration. RESULTS: A 69% (95%CI: 60-77%) showed some type of non-adherence. A 66% (95 CI%: 57-75%) acknowledged some involuntary non-adherence: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (95 CI%: 9-22%) showed some voluntary non-adherence: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% forgot at least a dose a week in the last 12 months. Multivariate analysis identified as risk factors for a lower adherence the dosing in three or more takes a day (OR 3; 95%CI: 1.1-8.4; p=0.03) and feeling little informed about their disease (OR 4.9; 95%CI: 1.1-23.8; p=0.04). Immunomodulator therapy predicted better adherence (OR 0.29; 95%CI: 0.11-0.74; p=0.01). CONCLUSIONS: Adherence to therapy in inflammatory bowel disease patients is not satisfactory, and worse in patients treated with mesalazine. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adherence.

15 Article Mercaptopurine rescue after azathioprine-induced liver injury in inflammatory bowel disease. 2010

Bermejo, F / López-Sanromán, A / Algaba, A / Van-Domselaar, M / Gisbert, J P / García-Garzón, S / Garrido, E / Piqueras, B / De La Poza, G / Guerra, I. ·Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Madrid, Spain. fbermejos@medynet.com ·Aliment Pharmacol Ther · Pubmed #19709096.

ABSTRACT: BACKGROUND: Azathioprine (AZA) liver toxicity arises in approximately 3% of inflammatory bowel disease patients and may result in treatment discontinuation. AIM: To describe the tolerance to mercaptopurine (MP) in patients with previous AZA-related liver injury. METHODS: Retrospective description of 31 patients (14 Crohn's, 17 ulcerative colitis), in which AZA therapy was interrupted because of liver injury, with MP started as alternative therapy. RESULTS: Mean AZA dose was 2.2 +/- 0.4 mg x kg/day. Median (interquartile range) of AZA exposure when liver injury was detected was 2 months (1-5.2). The type of AZA-related injury was cytolitic in 32%, cholestatic in 39% and mixed in 29%. After a median of 2.5 months (0.7-5.2), the therapy was switched to MP at a mean dose of 1.3 +/- 0.2 mg x kg/day. Median of follow-up of MP therapy was 32 months (8-54). In 87.1% of patients (95%CI: 70-96%), MP was tolerated without further liver injury; of these, 77.4% tolerated full MP doses and 9.7% tolerated lower doses. In a further cohort of 12.9% of patients, (95%CI: 3-29%), liver injury reappeared (two cholestasis, two mixed), 1-3 months after the onset of MP exposure. CONCLUSION: The administration of MP is a good alternative in patients with AZA-related liver injury, before thiopurines are definitely discarded.