Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab.

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.

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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Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry.

BACKGROUND: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. METHODS: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. RESULTS: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. CONCLUSIONS: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

Trasplante de precursores hematopoyéticos en enfermedad de Crohn refractaria: experiencia en nuestro centro / Autologous haematopoietic stem cell transplantation in refractory Crohn's disease: Experience in our centre

Introducción: El trasplante autólogo de precursores hematopoyéticos (TPHA) es una modalidad de tratamiento aceptada para la enfermedad de Crohn (EC) refractaria. Material y métodos: Se recogen los pacientes con EC refractaria sometidos a TPHA en el hospital Universitario Ramón y Cajal de Madrid y se describen de forma retrospectiva los resultados obtenidos. Resultados: Un total de 7 pacientes han recibido TPHA debido a EC refractaria en nuestro centro. Tres pacientes (43%) presentaron remisión clínica y endoscópica; un paciente (14%) mejoría clínica sin remisión y 3 pacientes (43%) permanecían activos con necesidad de reinicio del tratamiento en la valoración de la respuesta inicial al TPHA (a 6 meses). Los síntomas recurrieron en 5 de los 7 pacientes (71%), y todos ellos requirieron reinicio de tratamiento médico a una media de 13,8 meses (rango: 3-30 meses). Solo un paciente requirió cirugía tras el TPHA. Al final del seguimiento a una media de 48 meses (rango: 17-78 meses) 5/7 (71%) de los pacientes estaban en remisión clínica con o sin tratamiento. Conclusión: El TPHA puede ser una opción terapéutica prometedora para pacientes con EC refractaria. Su utilidad radica en que puede producir la remisión clínica sin tratamiento en algunos pacientes, pero también en que puede hacer la enfermedad tratable, consiguiendo respuesta a determinados tratamientos en pacientes que la habían perdido previamente

Introduction: Autologous haematopoietic stem cell transplantation (AHSCT) is an accepted treatment in refractory Crohn's disease (CD). Material and methods: Data on patients with refractory CD subjected to AHSCT are collected at the Hospital Universitario Ramón y Cajal in Madrid and the results obtained are described retrospectively. Results: Seven patients in total have received AHSCT due to refractory CD in our centre. Three patients (43%) presented with clinical and endoscopic remission; one patient (14%) clinical improvement without remission and three patients (43%) remained active with the need to restart treatment in the assessment of the initial response to the AHSCT (after six months). Symptoms recurred in five of the seven patients (71%) and all of them had to restart medical treatment after an average of 13.8 months (range: 3-30 months). Only one patient needed surgery after the AHSCT. At the end of the follow-up, after a mean of 48 months (range: 17-78 months), 5/7 (71%) of the patients were in clinical remission with or without treatment. Conclusion: AHSCT may be a promising therapeutic option for patients with refractory CD. Its usefulness lies in the fact that it can produce clinical remission without treatment in some patients, but also that it can make the disease treatable, obtaining a response to certain treatments in patients who had previously lost it

Autologous haematopoietic stem cell transplantation in refractory Crohn's disease: Experience in our centre. / Trasplante de precursores hematopoyéticos en enfermedad de Crohn refractaria: experiencia en nuestro centro.

INTRODUCTION: Autologous haematopoietic stem cell transplantation (AHSCT) is an accepted treatment in refractory Crohn's disease (CD). MATERIAL AND METHODS: Data on patients with refractory CD subjected to AHSCT are collected at the Hospital Universitario Ramón y Cajal in Madrid and the results obtained are described retrospectively. RESULTS: Seven patients in total have received AHSCT due to refractory CD in our centre. Three patients (43%) presented with clinical and endoscopic remission; one patient (14%) clinical improvement without remission and three patients (43%) remained active with the need to restart treatment in the assessment of the initial response to the AHSCT (after six months). Symptoms recurred in five of the seven patients (71%) and all of them had to restart medical treatment after an average of 13.8 months (range: 3-30 months). Only one patient needed surgery after the AHSCT. At the end of the follow-up, after a mean of 48 months (range: 17-78 months), 5/7 (71%) of the patients were in clinical remission with or without treatment. CONCLUSION: AHSCT may be a promising therapeutic option for patients with refractory CD. Its usefulness lies in the fact that it can produce clinical remission without treatment in some patients, but also that it can make the disease treatable, obtaining a response to certain treatments in patients who had previously lost it.

Enteropatía pierde-proteínas resuelta tras la reparación de una eventración abdominal / Protein-losing enteropathy resolved after ventral abdominal hernia repair

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Trasplante de microbiota fecal: indicaciones, metodología y perspectivas futuras / Faecal microbiota transplantation: indications, methodology and future prospects

La microbiota intestinal se define como el conjunto de microorganismos que habitan de forma natural en el tubo digestivo. Bacterias, hongos y virus se incluyen dentro de este ente fisiológico que va mucho más allá de ser un mero espectador pasivo de la mucosa intestinal. La microbiota interviene de forma activa en la homeostasis y su desregulación se ha relacionado con múltiples enfermedades de naturaleza infecciosa, metabólica y autoinmunitaria. El trasplante de microbiota fecal (TMF) consiste en la introducción de una solución de materia fecal debidamente procesada procedente de un donante sano en el tracto gastrointestinal de otro individuo con el fin de manipular las características de la microbiota del receptor. Aunque pueda parecer algo novedoso, los primeros casos se remontan a la época de la China Imperial; no obstante, no ha sido hasta los últimos 20 años cuando el interés y la actividad investigadora en este campo se han multiplicado de forma exponencial. Fruto de este trabajo el TMF constituye hoy en día una herramienta eficaz y validada en casos refractarios de diarrea por C. Difficile. Aunque la evidencia científica es menor, ya existen ensayos clínicos que evalúan su beneficio en la enfermedad inflamatoria intestinal y en el síndrome metabólico. Lo atractivo de su mecanismo fisiopatológico, la sencillez del procedimiento y su bajo coste lo sitúan como un tratamiento prometedor en múltiples enfermedades extradigestivas. El objetivo de esta revisión es resumir de una forma concisa, rigurosa y actualizada las indicaciones, metodología y seguridad del TMF.

The intestinal microbiota is defined as the set of organisms that live in the digestive tract. Bacteria, fungi and viruses are included in a physiological entity that goes far beyond being a passive spectator of the intestinal mucosa. The microbiota is actively involved in homeostasis and its imbalance has been linked to multiple infectious, metabolic and autoimmune diseases. Fecal microbiota transplantation (FMT) consists in the introduction of a solution made with processed stool from a healthy donor into the gastrointestinal tract of another individual in order to manipulate the characteristics of the receiver microbiota. Although it may seem new, the first cases date back to the days of Imperial China; however, it was not until the past 20 years when the interest and research in this field have grown exponentially. Nowadays, TMF is an effective and validated treatment in refractory cases of C.difficile diarrhea. Although the scientific evidence is less, there are clinical trials evaluating its benefit in inflammatory bowel disease and metabolic syndrome. The appeal of its pathophysiological mechanism, the simplicity of the procedure and its low cost place FMT as a promising treatment for multiple extraintestinal diseases. The objective of this review is to summarize in a concise, thorough and updated form its indications, methodology and safety.

Esteroides en enfermedad inflamatoria intestinal / No disponible

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Hepatotoxicidad secundaria a enoxaparina / Enoxaparin-induced hepatotoxicity

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

Introducción Los salicilatos son el tratamiento de elección en la fase de mantenimiento de la colitis ulcerosa. El primer salicilato fue la sulfasalazina, prácticamente sustituida por la mesalazina por su supuesta mejor tolerancia. Estudios recientes indican que la mesalazina podría ser menos eficaz que la sulfasalazina. Nos planteamos si los pacientes mal controlados con mesalazina en fase de mantenimiento podrían responder a sulfasalazina antes de progresar a inmunosupresores o biológicos. Métodos De los pacientes con colitis ulcerosa de la consulta de Enfermedad Inflamatoria Intestinal del Hospital Ramón y Cajal, seleccionamos los tratados con mesalazina y en los que la sulfasalazina se había utilizado como tratamiento de mantenimiento de rescate. Determinamos qué porcentaje de pacientes insuficientemente controlados con mesalazina respondieron a sulfasalazina. Resultados De 415 pacientes con colitis ulcerosa, 49 habían tomado SSZ en algún momento. En 31, este tratamiento se indicó como alternativa a la ineficacia de la mesalazina. El tiempo medio de tratamiento con mesalazina antes del cambio había sido de 20,8 meses, siendo la dosis media utilizada de 3,35g/día. La dosis media de sulfasalazina empleada fue de 2,5g/día. En 21 de los 31 pacientes (67,7%) se consiguió mantener la remisión con la sulfasalazina. Conclusión A pesar de las limitaciones de nuestro estudio, en el 67,7% de los pacientes con colitis ulcerosa mal controlados con mesalazina, el cambio a sulfasalazina resultó eficaz. Dado que se trata de pacientes en los que el siguiente paso sería el empleo de inmunosupresores o biológicos, creemos que esta opción merece estudios controlados y que en todo caso la sulfasalazina no debe desterrarse en el manejo de pacientes con colitis ulcerosa(AU)

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 3.35g/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 (AU)

Does active smoking really influence the course of Crohn's disease? A retrospective observational study.

BACKGROUND: Active smoking has been associated with a higher risk of developing Crohn's disease (CD). However, its impact on clinical outcomes has been controversial among studies. AIMS: To evaluate the influence of active smoking on initial manifestations of CD, the development of disease-related complications, and therapeutic requirements. METHODS: Patients diagnosed with CD within a ten-year period (1994-2003) were identified. Clinical and therapeutic features until October 2008 or loss of follow-up were recorded. Smoking status was assessed at each major disease-related event (e.g. penetrating and stricturing complications, perianal disease, intestinal resection, introduction of immunomodulators or biological agents). RESULTS: A total of 259 patients were included in the study with a median follow-up period of 91 months. At diagnosis, 50.5% were active smokers and only 12% of them quit smoking during follow-up, mostly after a major disease-related event occurred. Smoking at diagnosis was not associated with a particular CD presentation. Active smoking did not influence the development of strictures, intraabdominal and perianal penetrating complications, or increased resectional surgery, biological therapy or immunomodulators requirements. CONCLUSIONS: Patients who develop CD while smoking seem to have a similar disease course to those who never smoked.

[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.

Herpes zoster motor neuropathy in a patient with previous motor paresis secondary to Vogt-Koyanagi-Harada disease.

Motor involvement in herpes zoster is very infrequent, occurring in 3%-5% of cases, and it is caused by extension of the inflammatory process to the anterior horn motor neurons, with the subsequent development of segmental motor paralysis. The authors report a 37-yr-old woman with history of paresis in both lower limbs secondary to spinal cord atrophy associated with Vogt-Koyanagi-Harada disease and immunosuppression caused by chronic corticosteroid and azathioprine treatment of ulcerative colitis, who developed worsening of her baseline residual muscle strength in the right lower limb shortly after herpes zoster eruption. Electromyography revealed acute denervation in territories corresponding to L3-L4 and moderate widespread axonal polyneuropathy affecting both lower limbs. The patient recovered her baseline muscle strength after this event. To the best of the authors' knowledge, this is the first reported case of herpes zoster motor neuropathy in a patient with a previous motor sequel.