Real-world long-term effectiveness of ustekinumab in ulcerative colitis: results from a spanish open-label cohort.

OBJECTIVE: Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients. METHODS: Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented. RESULTS: A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively. CONCLUSIONS: Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients.

Use of digital health tools in inflammatory bowel disease. / Uso de herramientas digitales en salud en enfermedad inflamatoria intestinal.

OBJECTIVE: To analyse the characteristics and use of digital health tools (DHT) in inflammatory bowel disease (IBD). METHODS: We performed a qualitative study based on a narrative literature review, a questionnaire and on the opinion of 3 expert gastroenterologists. Several searches were carried out until September 2022 through Medline to identify articles on the use of DHT in IBD by healthcare professionals. A structured questionnaire was designed to be answered by health professionals involved in the care of patients with IBD. The experts generated a set of recommendations. RESULTS: There are multiple DHT for IBD with different characteristics and contents. We received 29 questionnaires. Almost 50% of the participants were 41-50 years old, the majority were women (83%) and 90% were gastroenterologists. A total of 96% reported the use of several DHT, but 20% used them occasionally or infrequently. Web pages were found the most used (62%). DHT are mostly used to get information (80%), followed by clinical practice issues (70%) and educational purposes (62%). G-Educainflamatoria website is the best known and most used HDS (96% and 64%, respectively). The main barriers to the use of DHT in IBD were the lack of time (55%), doubts about the benefit of DHT (50%) and the excess of information (40%). CONCLUSIONS: Healthcare professionals involved in the care of patients with to IBD frequently use DHT, although actions are needed to optimize their use and to guarantee their efficient and safe use.

Position statement of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis on sexuality and inflammatory bowel disease. / Documento de posicionamiento. Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa sobre sexualidad y enfermedad inflamatoria intestinal.

It is widely acknowledged that inflammatory bowel disease (IBD) is associated with a high prevalence of sexual dysfunction (SD). However, there is a notable paucity of specific literature in this field. This lack of information impacts various aspects, including the understanding and comprehensive care of SD in the context of IBD. Furthermore, patients themselves express a lack of necessary attention in this area within the treatment of their disease, thus creating an unmet need in terms of their well-being. The aim of this position statement by the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) is to provide a review on the most relevant aspects and potential areas of improvement in the detection, assessment, and management of SD in patients with IBD and to integrate the approach to sexual health into our clinical practice. Recommendations are established based on available scientific evidence and expert opinion. The development of these recommendations by GETECCU has been carried out through a collaborative multidisciplinary approach involving gastroenterologists, gynecologists, urologists, surgeons, nurses, psychologists, sexologists, and, of course, patients with IBD.

Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort.

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Exocrine pancreatic insufficiency and graft-versus-host disease.

We present the case of a 59-year-old man with acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two years later, he consulted for diarrhea and steatorrhea of 2-3 months of evolution with significant weight loss. Stool cultures and study of parasites were negative. Thyroid and celiac profile, cytomegalovirus viremia and colonoscopy, were normal. Fecal calprotectin and fecal clearance of alpha-1-Antitrypsin were normal but with almost undetectable fecal elastase (<15 ug/g). Pancreatic magnetic resonance reveals a generalized atrophy of the pancreas without other parenchymal or ductal alterations. The patient had no risk factors for chronic pancreatitis and was diagnosed with exocrine pancreatic insufficiency (EPI) associated with chronic graft-versus-host disease (GVHD). GVHD is caused by an immune-mediated reaction by donor T cells recognizing foreign antigens from the recipient. GVHD occurs in 80% of patients after allo-HSCT. Diarrhea is one of the most frequent manifestations, most often due to intestinal damage, opportunistic infections or chemoradiation effects.

Current management of bowel failure due to Crohn's disease in Spain: Results of a GETECCU survey. / Manejo actual del fracaso intestinal por enfermedad de Crohn en nuestro medio: resultados de una encuesta GETECCU.

INTRODUCTION: Intestinal failure is a rare pathology which requires knowledge and highly specialized multidisciplinary management. Crohn's disease (CD) being one of the most frequent causes in adults. MATERIAL AND METHODS: Survey format study carried out within the GETECCU group, included closed format questions about the diagnosis, management and current knowledge of intestinal failure in CD. RESULTS: Forty-nine doctors participated, belonging to different Spanish centers (19 cities). It was considered that a patient suffered from intestinal failure, in 67.3% (33/49 surveyed) when there was a disorder malabsorptive associated regardless of the intestinal length resected, with surgeries resective ileal repeated (40.8%, 20/49), the most frequent cause. It highlights frequent ignorance about the pathology (24.5%) did not know if there were patients in their center and also 40% did not know the pharmacological treatment. A total of 228 patients were registered for follow-up due to intestinal failure of any aetiology, 89 patients (39.5%) were identified with CD. Regarding the therapeutic management of patients with CD and intestinal failure (72.5%) were receiving total parenteral nutrition (NTP) and 24 patients (27%) with teduglutide. Regarding the response to the drug: 37.5% had no response to teduglutide, 37.5% partial response (reduce NTP) and 25% good response (withdrawal of home NTP). In questions related to knowledge about intestinal failure, it was considered limited (53.1%) or very limited (12.2%) by the surveyed. CONCLUSION: It is necessary to carry out a combined management of intestinal failure and CD in the context of a multidisciplinary approach.

Anti-tumor necrosis factor agents in Crohn's disease and ulcerative colitis: Beyond luminal disease. / Agentes anti-factor de necrosis tumoral en enfermedad de Crohn y colitis ulcerosa: más allá de la enfermedad luminal.

Anti-tumor necrosis factor agents (anti-TNF) drugs are commonly used in patients with inflammatory bowel disease (IBD) and have proven effective in both induction and maintenance therapy in luminal Crohn's disease and ulcerative colitis. Their efficacy has also been proven in fistulising perianal Crohn's disease. However, the evidence in other scenarios, such as stricturing, penetrating and non-fistulising perianal Crohn's disease, extraintestinal IBD manifestations and ileoanal reservoir complications, is not as robust. The aim of this review was to perform an analysis of the available literature and to determine the role of anti-TNF drugs in common clinical practice in patients affected by these complications.

Clinical experience of optimising thiopurine use through metabolite measurement in inflammatory bowel disease. / Experiencia en práctica clínica de optimización de tiopurinas mediante determinación de sus metabolitos en la enfermedad inflamatoria intestinal.

INTRODUCTION: Thiopurine therapy can be optimised by determining the concentration of the drug's metabolites. PATIENTS AND METHODS: Retrospective analysis on a prospective database of 31 patients with inflammatory bowel disease who failed therapy with thiopurines. Thiopurine metabolites (6-thioguanine, 6-TGN and 6-methylmercaptopurine, 6-MMP) were measured by high-performance liquid chromatography (Laboratorios Cerba, Barcelona) and treatment was duly adjusted in accordance with the results. Clinical response was reassessed after six months. RESULT: Despite the appropriate theoretical dose of thiopurines being administered, the dose was insufficient in 45.6% of patients (nonadherence to treatment suspected in 6.45%) and 16.2% received an excessive dose or the drug was metabolised by other metabolic pathways. After treatment was optimised based on metabolite levels, only 25.8% (8/31) were prescribed a biological agent, while 74.2% of cases (23/31) were managed through dose optimisation alone. DISCUSSION: Monitoring thiopurine metabolite levels may help clinicians to assess non-responsive patients before adding or switching to another drug (generally a biological agent), thereby avoiding any additional costs or potential toxicity. This strategy may also help to identify patients receiving an insufficient dose and those with an alternative metabolic pathway, who could be candidates for low-dose AZA with allopurinol, as well as patients who are suspected of being non-adherent. In three out of four patients, switching to a biological agent can be avoided.

[Rescue therapy with sulfasalazine prior to immunosuppressive or biological agents in ulcerative colitis poorly controlled with mesalazine]. / Rescate con sulfasalazina antes de inmunosupresores o agentes biológicos en la colitis ulcerosa mal controlada con mesalazina.

INTRODUCTION: In ulcerative colitis, aminosalicylates are the mainstay of maintenance therapy. Sulfasalazine was the first aminosalicylic used in the maintenance therapy of this disease. Later, mesalazine was preferred due to its supposedly better tolerability. However, recent studies indicate certain benefits of the use of sulfasalazine because of its possible superior effectiveness. The aim of this study was to determine whether patients with ulcerative colitis poorly controlled by mesalazine as maintenance therapy respond to sulfasalazine, thus avoiding the use of immunosuppressive or biological therapies. METHODS: The Inflammatory Bowel Disease Clinic of the Ramón y Cajal Hospital maintains a database in which all drug exposures are registered. We selected patients poorly controlled with mesalazine who had received sulfasalazine as rescue maintenance therapy. We determined the percentage of patients poorly controlled with mesalazine who responded to sulfasalazine. RESULTS: Of 415 patients with ulcerative colitis, 49 had been treated with sulfasalazine at some time. Of these, sulfasalazine was selected as an alternative therapy due to poor disease control with mesalazine. The median duration of mesalazine therapy until the switch was 20.8 months, with a median dose of 3.35 g/day. In 21 of the 31 patients (67.7%), sulfasalazine was able to control symptoms and maintain remission. CONCLUSION: Despite the limitations of this study, we found that 67.7% of patients with ulcerative colitis poorly controlled with mesalazine responded to a switch to sulfasalazine. These patients would normally have progressed to immunosuppressive, biological or surgical treatments. This option merits further studies. Meanwhile sulfasalazine should not be forgotten in the management of ulcerative colitis.

[Octreotide treatment for postoperative chylous ascites in an adult]. / Ascitis quilosa posquirúrgica en un adulto tratada con octreótida.

Chylous ascites is infequent after abdominal surgery. We describe the case of a 43-year-old man with portal cavernomatosis who underwent surgery to insert a splenorenal shunt, which was not placed due to the absence of signs of portal hypertension. On postoperative day 20, the patient developed abdominal distension and mild dyspnea and was diagnosed with chylous ascites, which was related to the surgery. The patient was initially treated with diet and diuretics, with no clinical response, and consequently octreotide therapy was started. Four days later, the ascites was almost resolved and an ultrasound scan at 4 months showed its complete disappearance. This article demonstrates the effectiveness of octreotide in the treatment of postsurgical chylous ascites.

[An exceptional cause of acute hepatitis in an adult: parvovirus B19]. / Una causa excepcional de hepatitis aguda en el adulto: parvovirus B19.

There are multiple causes of hepatitis. The most frequent etiologies are viral, usually hepatitis A, B and C viruses. However, other, non-hepatotropic viruses can cause this disease, including parvovirus B19. We present a case of acute hepatitis due to parvovirus B19, as well as a review of the epidemiological, clinical, diagnostic and therapeutic features of this entity.

The Impact of Vedolizumab and Ustekinumab on Articular Extra-Intestinal Manifestations in Inflammatory Bowel Disease Patients: A Real-Life Multicentre Cohort Study.

BACKGROUND AND AIMS: Extra-intestinal manifestations are frequently reported in inflammatory bowel diseases. However, data comparing the effect of vedolizumab and ustekinumab on articular extra-intestinal manifestations are limited. The aim here was to evaluate differences in new-onset and the evolution of pre-existing joint extra-intestinal manifestations during both treatments. METHODS: An international multicentre retrospective study was performed on inflammatory bowel disease patients who started vedolizumab or ustekinumab between May 2010 and December 2020. Extra-intestinal manifestations were assessed at baseline and joint extra-intestinal manifestations were evaluated throughout the 2-year follow-up. Arthropathy was defined by joint inflammation [arthritis/sacroiliitis], diagnosed by a rheumatologist, and arthralgia as articular pain without confirmed inflammation. Additionally, skin, ocular and hepatic extra-intestinal manifestations were assessed at baseline. Uni- and multivariate analyses were performed. RESULTS: In total, 911 patients [vedolizumab: 584; ustekinumab: 327] were included. Deterioration of pre-existing arthropathy and rate of new-onset arthropathy were not significantly associated with vedolizumab over ustekinumab. Arthropathy was used as reason to stop treatment in six vedolizumab and two ustekinumab patients. The odds of developing new arthralgia within 6 months was higher in patients who took vedolizumab compared to ustekinumab (adjusted odds ratio [aOR]: 2.28 [1.01-5.15], p = 0.047). However, this effect was not sustained during the 2-year follow-up (aOR: 1.35 [0.80-2.29], p = 0.259). Deterioration of pre-existing arthralgia was comparable between ustekinumab and vedolizumab-treated patients. In two vedolizumab-treated patients arthralgia was given as the reason to stop treatment. CONCLUSIONS: Vedolizumab and ustekinumab can be used safely in patients with articular extra-intestinal manifestations. Only a temporary increased risk for developing arthralgia has been observed under vedolizumab.

Colitis ulcerosa y bronquiectasias: ¿el tratamiento con tofacitinib podría repercutir en los síntomas respiratorios? / Ulcerative Colitis and Bronchiectasis: Can Treatment with Tofacitinib Have an Impact on Respiratory Symptoms?

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Antidepresivos y su relación con la colitis microscópica / Antidepressants and its relationship with microscopic colitis

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Agentes anti-factor de necrosis tumoral en enfermedad de Crohn y colitis ulcerosa: más allá de la enfermedad luminal / Anti-tumor necrosis factor agents in Crohn's disease and ulcerative colitis: Beyond luminal disease

Los agentes anti-factor de necrosis tumoral (anti-TNF) son fármacos de uso común en los pacientes con enfermedad inflamatoria crónica intestinal (EICI) y han demostrado ser efectivos en inducción y mantenimiento en enfermedad de Crohn y colitis ulcerosa, así como en pacientes con afectación fistulizante perianal. Sin embargo, la evidencia relativa al uso de estos fármacos en otros escenarios dentro de EICI es menos sólida. Es el caso de la enfermedad de Crohn con afectación estenosante, penetrante o perianal no fistulizante, de las manifestaciones extraintestinales de la EICI y de las complicaciones del reservorio ileoanal. El objetivo de esta revisión fue realizar un análisis de la literatura disponible y determinar el papel de los anti-TNF en la práctica clínica en pacientes afectos por estas complicaciones

Anti-tumor necrosis factor agents (anti-TNF) drugs are commonly used in patients with inflammatory bowel disease (IBD) and have proven effective in both induction and maintenance therapy in luminal Crohn's disease and ulcerative colitis. Their efficacy has also been proven in fistulising perianal Crohn's disease. However, the evidence in other scenarios, such as stricturing, penetrating and non-fistulising perianal Crohn's disease, extraintestinal IBD manifestations and ileoanal reservoir complications, is not as robust. The aim of this review was to perform an analysis of the available literature and to determine the role of anti-TNF drugs in common clinical practice in patients affected by these complications

Experiencia en práctica clínica de optimización de tiopurinas mediante determinación de sus metabolitos en la enfermedad inflamatoria intestinal / Clinical experience of optimising thiopurine use through metabolite measurement in inflammatory bowel disease

INTRODUCCIÓN: El tratamiento con tiopurinas puede optimizarse determinando la concentración de sus metabolitos. PACIENTES Y MÉTODOS: Análisis retrospectivo sobre una base de datos prospectiva, con inclusión de 31 pacientes con enfermedad inflamatoria intestinal en tratamiento con tiopurinas, que presentaban respuesta insuficiente. Se determinaron los metabolitos de tiopurinas en plasma (6-tioguanina, 6-TGN y 6-metilmercaptopurina, 6-MMP) por cromatografía líquida de alta eficacia (Laboratorios Cerba, Barcelona) ajustando el tratamiento de acuerdo a resultados. Tras 6 meses se reevaluó la respuesta clínica. RESULTADO: A pesar de la dosis adecuada teórica de tiopurinas un 45,6% de los pacientes estaba infradosificado (sospechándose falta de adhesión al tratamiento en un 6,45% del total) y un 16,2% sobredosificado o metabolizaba por ruta metabólica alternativa. Tras ajustar a partir de niveles de metabolitos, solo el 25,8% (8/31) requirió biológico, mientras que el 74,2% de los casos (23/31) se manejó mediante optimización. DISCUSIÓN: La monitorización del tratamiento con tiopurinas mediante determinación de sus metabolitos puede ser utilizada para valorar pacientes no respondedores, antes de sustituir o complementar dichos fármacos con otros alternativos (biológicos, por lo general), con los consiguientes aumentos de toxicidad potencial y coste. Se puede rescatar a pacientes infradosificados, identificar aquellos que presentan una desviación en la ruta metabólica en los que se podría plantear una terapia con dosis bajas de AZA asociada a alopurinol, o aquellos en los que los datos sugieran falta de adhesión al tratamiento. En 3 de cada 4 pacientes puede evitarse la escalada a biológico

INTRODUCTION: Thiopurine therapy can be optimised by determining the concentration of the drug's metabolites. PATIENTS AND METHODS: Retrospective analysis on a prospective database of 31 patients with inflammatory bowel disease who failed therapy with thiopurines. Thiopurine metabolites (6-thioguanine, 6-TGN and 6-methylmercaptopurine, 6-MMP) were measured by high-performance liquid chromatography (Laboratorios Cerba, Barcelona) and treatment was duly adjusted in accordance with the results. Clinical response was reassessed after six months. RESULT: Despite the appropriate theoretical dose of thiopurines being administered, the dose was insufficient in 45.6% of patients (nonadherence to treatment suspected in 6.45%) and 16.2% received an excessive dose or the drug was metabolised by other metabolic pathways. After treatment was optimised based on metabolite levels, only 25.8% (8/31) were prescribed a biological agent, while 74.2% of cases (23/31) were managed through dose optimisation alone. DISCUSSION: Monitoring thiopurine metabolite levels may help clinicians to assess non-responsive patients before adding or switching to another drug (generally a biological agent), thereby avoiding any additional costs or potential toxicity. This strategy may also help to identify patients receiving an insufficient dose and those with an alternative metabolic pathway, who could be candidates for low-dose AZA with allopurinol, as well as patients who are suspected of being non-adherent. In three out of four patients, switching to a biological agent can be avoided