ABSTRACT
BACKGROUND: Ustekinumab (UST) is commonly used to treat Crohn's disease and ulcerative colitis. However, some patients may experience diminishing response or require increased dosage. Intravenous (IV) UST maintenance is explored as a solution. OBJECTIVES: We sought to evaluate IV UST maintenance effectiveness and safety in inflammatory bowel disease patients with partial or lost subcutaneous UST response. METHODS: This was a multicenter retrospective study of inflammatory bowel disease patients on IV UST maintenance. Clinical response and remission at weeks 12 and 52, defined as Harvey-Bradshaw Index ≤4 for Crohn's disease or partial Mayo score ≤2 for ulcerative colitis. Objective markers reduction (fecal calprotectin, C-reactive protein), UST trough levels pre- and post-IV maintenance, and adverse events were assessed. RESULTS: A total of 59 patients were included. Clinical remission at weeks 12 and 52 achieved by 47.5% and 64.3% respectively. 96.6% continued IV UST at follow-up. UST serum levels quadrupled. No adverse events reported. CONCLUSIONS: IV UST maintenance effectively sustained remission in most patients at 52 weeks.
When patients lose response to subcutaneous ustekinumab, strategies include reinduction, interval shortening, and less explored intravenous maintenance. Its high rescue rate and safety profile make it a valuable option for managing active inflammatory bowel disease.
ABSTRACT
El tratamiento de la enfermedad inflamatoria intestinal (EII) ha sufrido una gran transformación tras la introducción de los fármacos biológicos. Gracias a ellos, los objetivos del tratamiento han evolucionado desde la respuesta y remisión clínica a objetivos más ambiciosos, como la remisión endoscópica o radiológica. Sin embargo, aunque los biológicos son muy eficaces, un porcentaje importante de pacientes no obtendrá una respuesta inicial o la perderá a lo largo del tiempo. Sabemos que existe una relación directa entre las concentraciones valle del biológico y su eficacia terapéutica, que cuanto más exigente sea el objetivo terapéutico serán necesarios niveles superiores del fármaco y que es frecuente la exposición insuficiente al mismo. La monitorización terapéutica de medicamentos biológicos, así como los modelos farmacocinéticos, nos brindan la posibilidad de ofrecer un enfoque personalizado del abordaje en pacientes con EII. Durante los últimos años se ha acumulado información relevante respecto a su utilidad durante o después de la inducción, así como en el mantenimiento del tratamiento biológico, en estrategias reactivas o proactivas y antes de la retirada o desintensificación del esquema.El objetivo de este documento es establecer recomendaciones sobre la utilidad de la monitorización terapéutica de biológicos en pacientes con EII, en los diferentes escenarios de la práctica clínica e identificar las áreas donde su utilidad es evidente, prometedora o controvertida. (AU)
The treatment of inflammatory bowel disease has undergone a significant transformation following the introduction of biologic drugs. Thanks to these drugs, treatment goals have evolved from clinical response and remission to more ambitious objectives, such as endoscopic or radiologic remission. However, even though biologics are highly effective, a significant percentage of patients will not achieve an initial response or may lose it over time. We know that there is a direct relationship between the trough concentrations of the biologic and its therapeutic efficacy, with more demanding therapeutic goals requiring higher drug levels, and inadequate exposure being common.Therapeutic drug monitoring of biologic medications, along with pharmacokinetic models, provides us with the possibility of offering a personalized approach to treatment for patients with IBD. Over the past few years, relevant information has accumulated regarding its utility during or after induction, as well as in the maintenance of biologic treatment, in reactive or proactive strategies, and prior to withdrawal or treatment de-escalation.The aim of this document is to establish recommendations regarding the utility of therapeutic drug monitoring of biologics in patients with inflammatory bowel disease, in different clinical practice scenarios, and to identify areas where its utility is evident, promising, or controversial. (AU)
Subject(s)
Humans , Inflammatory Bowel Diseases , Crohn Disease , Colitis, Ulcerative , Pharmacokinetics , Spain , Drug Monitoring , eHealth StrategiesABSTRACT
The treatment of inflammatory bowel disease has undergone a significant transformation following the introduction of biologic drugs. Thanks to these drugs, treatment goals have evolved from clinical response and remission to more ambitious objectives, such as endoscopic or radiologic remission. However, even though biologics are highly effective, a significant percentage of patients will not achieve an initial response or may lose it over time. We know that there is a direct relationship between the trough concentrations of the biologic and its therapeutic efficacy, with more demanding therapeutic goals requiring higher drug levels, and inadequate exposure being common. Therapeutic drug monitoring of biologic medications, along with pharmacokinetic models, provides us with the possibility of offering a personalized approach to treatment for patients with IBD. Over the past few years, relevant information has accumulated regarding its utility during or after induction, as well as in the maintenance of biologic treatment, in reactive or proactive strategies, and prior to withdrawal or treatment de-escalation. The aim of this document is to establish recommendations regarding the utility of therapeutic drug monitoring of biologics in patients with inflammatory bowel disease, in different clinical practice scenarios, and to identify areas where its utility is evident, promising, or controversial.
Subject(s)
Biological Products , Colitis, Ulcerative , Crohn Disease , Drug Monitoring , Humans , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Biological Products/therapeutic use , Biological Products/pharmacokinetics , Inflammatory Bowel Diseases/drug therapyABSTRACT
BACKGROUND: Therapeutic drug monitoring of infliximab levels in patients with inflammatory bowel disease (IBD) optimizes patients' treatment. The reference technique is based on enzyme-linked immunosorbent assay (ELISA) although point of care (POC) assays are being developed. AIMS: To assess the performance of a new rapid immunochromatographic POC assay (Promonitor Quick IFX) compared with ELISA technique to measure infliximab levels in patients with IBD. METHODS: A prospective, observational, unicentric study was performed on capillary blood samples from patients with IBD before infliximab infusion (trough levels). Infliximab levels and anti-infliximab antibodies were measured using the ELISA technique (Promonitor IFX) and the POC assay. Correlation between both techniques was assessed by Pearson's coefficient. Quantitative differences were evaluated by Bland-Altman analysis. Samples were stratified according to infliximab therapeutic ranges (< 3 µg/mL, 3-8 µg/mL, and > 8 µg/mL). RESULTS: A total of 135 experimental samples were assessed. Infliximab levels showed a high correlation between POC and ELISA tests (r = 0.84, P < 0.001). The mean difference between tests was 1.46 µg/mL (P < 0.001), being minimal for concentrations < 8 µg/mL. POC and ELISA assays showed an overall concordance of 87.4%. Most samples were in the same therapeutic range, which lead to equivalent therapeutic decisions. POC and ELISA assays detected the presence of anti-infliximab antibodies in 2.2% and 3.7% of the samples, respectively. CONCLUSIONS: POC assay results in blood samples from patients with IBD were comparable to those obtained with the reference ELISA technique. The POC assay could be considered for routine testing based on its ease of use and rapidity.
Subject(s)
Inflammatory Bowel Diseases , Humans , Drug Monitoring/methods , Enzyme-Linked Immunosorbent Assay/methods , Gastrointestinal Agents , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/drug therapy , Infliximab , Point-of-Care Testing , Prospective StudiesABSTRACT
BACKGROUND AND AIMS: The fully-covered self-expanding metal stent (SEMS) has a role in the management of refractory acute variceal haemorrhage. The aim of this study was to evaluate its effectiveness and complications in real-world practice. PATIENTS AND METHODS: An observational, descriptive, multicenter study was carried out. Eight patients with clinically significant portal hypertension who underwent a SEMS were included. RESULTS: SEMS placement controlled acute bleeding in 7 patients with technical success. Stents were removed after a median of 8 days. Rescue transjugular intrahepatic portosystemic shunt was performed around 48 hours after SEMS placement. Four patients survived after successful SEMS removal. The most common adverse event was stent loop in 2 patients. CONCLUSIONS: In our experience, SEMS was highly effective in controlling acute refractory variceal bleeding. Bleeding-related mortality rate was probably due to impossibility of TIPS implantation. Stent loop was a common limiting factor.
ABSTRACT
Background: Ustekinumab (UST) is indicated for the treatment of Crohn's disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world, some patients may lose response over time or need a higher dose to achieve it. In this context, UST intravenous (IV) maintenance has been proposed. Objectives: The primary endpoint of our study was to evaluate the efficacy and safety of maintenance IV UST treatment in Inflammatory Bowel Disease (IBD) patients who present with partial response or loss of response to subcutaneous (SC) UST. Design: We performed a monocentric observational retrospective study including patients with active IBD on maintenance treatment with IV UST. Methods: The clinical response and remission was analyzed at week 12, defined as either Harvey-Bradshaw Index ⩽ 4 for CD or partial Mayo Score ⩽ 2 for UC. The reduction of objective markers of disease activity, fecal calprotectin, and C-reactive protein was evaluated. Moreover, UST trough levels were measured pre- and post-UST IV maintenance and any adverse events were assessed. Results: We included 23 patients. Clinical remission at week 12 was achieved by 43.5% of the patients. The proportion of patients in clinical response after 12 weeks on UST IV maintenance was 82.6%. After a median follow-up of 9.3 months all patients remained on IV UST maintenance. No adverse events were recorded in any patient for the duration of the study. Conclusions: IV UST maintenance treatment was able to recapture response in most of the patients who had lost response to SC maintenance.
ABSTRACT
A 61-year-old male diabetic patient, diagnosed with ulcerative colitis (UC) 30 years ago, currently under treatment with mesalazine is presented. He was admitted to the emergency department due to a severe outbreak of UC, with 15 depositions daily, rectal bleeding and poor general condition. A brain CT-scan was carried out in the emergency department due to a sudden self-limited aphasia. A left frontal lesion of 45x38 mms with a prominent perilesional edema and with a displacement of the midline was reported. This was believed to be a meningioma (figure 1A). Urgent neurosurgery was not performed, prioritizing the severe flare-up UC. Based on this, full-dose metilprednisolone was administered.
Subject(s)
COVID-19 , Colitis, Ulcerative , Neoplasms , Male , Humans , Middle Aged , Colitis, Ulcerative/complications , Colitis, Ulcerative/drug therapy , Mesalamine , Disease OutbreaksABSTRACT
The incidence of extramammary Paget's disease (EMPD) is very low. It is very important to distinguish between primary Paget's disease and secondary to another process. An 85-year-old man consulted for the presence of an erythematous plaque located in the anal and gluteal area, confirming Paget cells in the biopsy.
Subject(s)
Breast Neoplasms , Paget Disease, Extramammary , Skin Neoplasms , Male , Humans , Aged, 80 and over , Paget Disease, Extramammary/diagnosis , Paget Disease, Extramammary/pathology , Skin Neoplasms/pathology , Anal Canal/pathology , Breast Neoplasms/pathology , BiopsySubject(s)
Humans , Male , Aged, 80 and over , Anus Neoplasms/diagnosis , Anus Neoplasms/pathology , Fatal OutcomeSubject(s)
Humans , Male , Middle Aged , Gastrinoma , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/surgery , Pancreas/pathology , Zollinger-Ellison Syndrome/pathology , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgeryABSTRACT
Antecedentes: ustekinumab es un anticuerpo monoclonal que inhibe las interleucinas IL-12 e IL-23, y está aprobado para el tratamiento de la enfermedad de Crohn (EC) y, más recientemente, también de la colitis ulcerosa (CU). El objetivo de este estudio fue evaluar la eficacia y seguridad de ustekinumab, así como identificar posibles factores predictivos de respuesta en un entorno de la vida real.Métodos: se realizó un estudio observacional, retrospectivo y multicéntrico en 4 hospitales de Andalucía. Se incluyeron pacientes adultos con diagnóstico confirmado de EC tratados con ustekinumab entre 2017 y 2019. Se analizó la respuesta clínica a los 3, 6 y 12 meses de tratamiento. La actividad clínica de la enfermedad se evaluó con el índice de Harvey-Bradshaw (HBI) y el índice de actividad de la enfermedad de Crohn (CDAI); La respuesta bioquímica se evaluó con parámetros de laboratorio como CRP y ESR. Se analizó la supervivencia al fármaco ustekinumab a un año.Resultados: Se analizaron un total de 98 pacientes (edad media, 43 años; el 52 % eran hombres); El 56 % había fracasado con ≥ 2 terapias biológicas previas. A los 3 meses, el 69 % de los pacientes estaban en respuesta y el 40,8 % en remisión. A los 6 meses, el 56 % estaba en remisión clínica. A los 12 meses, el 73,7 % estaba en respuesta clínica y el 60,5 % en remisión. La remisión sin corticosteroides fue del 32,4 %, 44 % y 47,4 % a los 3, 6 y 12 meses, respectivamente. La supervivencia acumulada tras un año de tratamiento con ustekinumab fue del 85,3 %. Los parámetros bioquímicos como CRP y ESR mostraron una disminución estadísticamente significativa entre los niveles de referencia y de control a los 3, 6 y 12 meses. Un HBI más bajo al inicio y el sexo femenino fueron predictores de remisión clínica libre de corticosteroides en un análisis univariante. (AU)
Subject(s)
Humans , Antibodies, Monoclonal/therapeutic use , Crohn Disease/drug therapy , Referral and Consultation , Ustekinumab/therapeutic use , Retrospective Studies , Treatment OutcomeABSTRACT
Zollinger Ellison syndrome is an unusual entity. This termn is used to describe the clinical manifestations of a gastrin-synthesizing neoplasm. Gastrinomas occur mainly in the duodenum and pancreas. Primary gastrinomas are rarely found in other intra-abdominal sites, such as the ovary, bile ducts, spleen or kidney, or even more unusual in extra-abdominal locations. Several studies provide strong evidence that gastrinomas can also occur in the lymph nodes. However, the existence of primary lymph node gastrinomas is controversial.
Subject(s)
Gastrinoma , Gastrointestinal Stromal Tumors , Pancreatic Neoplasms , Zollinger-Ellison Syndrome , Female , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/surgery , Humans , Pancreas/pathology , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Zollinger-Ellison Syndrome/pathologyABSTRACT
Introducción: el objetivo principal de este estudio fue evaluar la reducción de los síntomas gastrointestinales de pacientes con terapia de erradicación cuádruple con bismuto, complementada con cepas de Lactobacillus reuteri (DSM 17938 y ATCC PTA 6475), frente a un placebo.Materiales y métodos: ensayo clínico aleatorizado, doble ciego, de brazos paralelos y controlado con placebo. Los pacientes recibieron en primera línea el régimen erradicador basado en subcitrato de bismuto potásico, metronidazol, clorhidrato de tetraciclina (cápsulas tres en uno) y omeprazol 40 mg dos veces al día durante diez días, más un comprimido (probiótico o placebo) durante treinta días. En el seguimiento se evaluaron los síntomas gastrointestinales mediante una escala de valoración (GSRS) y los eventos adversos a los 0, 14, 28 y 56 días.Resultados: se incluyeron un total de 80 pacientes desde febrero de 2018 a mayo de 2019 en un solo centro. El tratamiento erradicador fue eficaz en el 85 % de los pacientes, sin diferencias entre los dos brazos de tratamiento. En el grupo que recibió el probiótico, el dolor abdominal se redujo en el 42 % de los pacientes, en comparación con el 19 % del grupo de control (OR: 0,27; IC 95 %: 0,13-0,58; p < 0,001), y la distensión abdominal se redujo un 25 %, frente a un 17 % en el grupo de control (OR: 0,24; IC 95 %: 0,19-0,84; p < 0,001).Conclusiones: el tratamiento con L. reuteri consiguió reducir solo el dolor y la distensión abdominal. Se necesitan más estudios para determinar la contribución de los probióticos como terapia adyuvante en la erradicación de H. pylori. (AU)
Subject(s)
Humans , Abdominal Pain/drug therapy , Abdominal Pain/therapy , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Bismuth/therapeutic use , Limosilactobacillus reuteri , Probiotics/therapeutic use , Drug Therapy , Helicobacter Infections/drug therapy , Metronidazole/adverse effectsABSTRACT
INTRODUCTION: the primary goal of this study was to compare gastrointestinal symptom reduction in patients on bismuth-containing quadruple eradication therapy supplemented with Lactobacillus reuteri strains (DSM 17938 and ATCC PTA 6475) or placebo. MATERIALS AND METHODS: this was a randomized, double-blind, parallel-arm, placebo-controlled clinical trial. Patients received a first-line eradication regimen based on bismuth subcitrate potassium, metronidazole, tetracycline hydrochloride (three-in-one capsules) and omeprazole 40 mg twice a day for ten days, plus a probiotic or placebo tablet for 30 days. During follow-up, gastrointestinal symptoms were assessed using an evaluation scale (GSRS), and adverse events were collected at 0, 14, 28 and 56 days. RESULTS: a total of 80 patients were included from February 2018 to May 2019 at a single site. Eradication therapy was effective in 85 % of patients, with no differences between treatment arms. In the group receiving the probiotic, abdominal pain decreased in 42 % of patients, compared with 19 % in the control group (OR: 0.27; CI, 0.13-0.58; p < 0.001), and abdominal distension decreased in 25 % versus 17 % in the control group (OR: 0.24; IC, 0.19-0.84; p < 0.001); Conclusions: treatment with L. reuteri only reduced abdominal pain and distension. Further studies are needed to establish the role of probiotics as adjuvant therapy in H. pylori eradication.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Limosilactobacillus reuteri , Probiotics , Abdominal Pain/drug therapy , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Bismuth/therapeutic use , Drug Therapy, Combination , Helicobacter Infections/drug therapy , Humans , Metronidazole/adverse effects , Probiotics/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: ustekinumab is a monoclonal antibody that inhibits interleukins IL-12 and IL-23, and is approved for the treatment of Crohn's disease (CD) and, more recently, also ulcerative colitis (UC). The aim of this study was to evaluate the effectiveness and safety of ustekinumab, as well as to identify possible predictive factors of response in a real-life setting. METHODS: an observational, retrospective, multicenter study was carried out in 4 hospitals in Andalusia. Adult patients with a confirmed diagnosis of CD treated with ustekinumab from 2017 to 2019 were included. Clinical response was analyzed at 3, 6 and 12 months of treatment. Clinical disease activity was assessed with the Harvey-Bradshaw index (HBI) and the Crohn's Disease Activity Index (CDAI); biochemical response was assessed with lab parameters such as CRP and ESR. One-year ustekinumab drug-survival was analyzed. RESULTS: a total of 98 patients were analyzed (mean age, 43 years; 52 % were male); 56 % had failed with ≥ 2 previous biologicals therapies. At 3 months, 69 % of the patients were in response and 40.8 % in remission. At 6 months, 56 % were in clinical remission. At 12 months, 73.7 % were in clinical response and 60.5 % in remission. Corticosteroid-free remission was 32.4 %, 44 %, and 47.4 % at 3, 6, and 12 months, respectively. Cumulative survival after one year of treatment with ustekinumab was 85.3 %. Biochemical parameters such as CRP and ESR showed a statistically significant decrease between baseline and control levels at 3, 6, and 12 months. A lower HBI at baseline and female sex were predictors of corticosteroid-free clinical remission in a univariate analysis. In the multivariate analysis no variables were found as predictors of corticosteroid-free clinical remission. CONCLUSION: ustekinumab therapy is safe and useful, inducing clinical response in more than 50 % of patients, including patients who failed with other biological therapies.
Subject(s)
Crohn Disease , Ustekinumab , Adult , Antibodies, Monoclonal/therapeutic use , Crohn Disease/drug therapy , Female , Humans , Male , Remission Induction , Retrospective Studies , Treatment Outcome , Ustekinumab/therapeutic useABSTRACT
Primary follicular lymphomas (FL) of the gastrointestinal (GI) tract are very rare and constitute < 4 % of all non-Hodgkin's lymphomas at this location. We report our experience with primary FL of the GI tract.
Subject(s)
Gastrointestinal Neoplasms , Intestinal Obstruction , Lymphoma, Follicular , Gastrointestinal Neoplasms/complications , Gastrointestinal Neoplasms/diagnostic imaging , Humans , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/etiology , Lymphoma, Follicular/complications , Lymphoma, Follicular/diagnostic imaging , MaleABSTRACT
Ischemic gastritis (IG) is an extremely rare entity due to the rich gastric vascularization. The present case is the ideal setting to suspect this condition.
Subject(s)
Diabetic Ketoacidosis , Gastritis , Diabetic Ketoacidosis/complications , Gastritis/diagnosis , Gastritis/diagnostic imaging , Humans , Ischemia/diagnostic imaging , Ischemia/etiologyABSTRACT
INTRODUCTION: between 30 % and 40 % of patients treated with infliximab lose response during maintenance. Therapeutic drug monitoring could be used to optimize management in these situations. However, infliximab serum levels are not well defined. The aim of this study was to determine the cut-off range of infliximab serum levels in Crohn's disease patients in remission in the clinical practice. METHODS: an observational retrospective study was performed from 2016 to 2017. Patients were included with established Crohn's disease, who had been on a maintenance dose schedule of infliximab. Infliximab levels and antibodies to infliximab were measured at least twice in all patients, after induction and after six months of treatment. Clinical remission was defined as ≤ 4 using the Harvey-Bradshaw index. Cluster analysis was used to analyze the results. RESULTS: one hundred and five Crohn's disease patients were included in the study; 57.1 % were male with a mean age of 39 years (SD ± 12.9). The median (range) time of the disease was eleven years (7-15) and the median (range) time of follow-up was 32 months (22-38). Patients who achieved remission had infliximab serum levels between 4.26-8.26 ug/ml versus 0.06-1.43 ug/ml in patients who did not achieve remission after induction. Infliximab serum levels were 2.84-7.75 ug/ml and 0.05-2.69 ug/ml in patients who achieved remission versus those who did not achieve remission after six months of treatment. Overall, 4.26-8.26 ug/ml was found to be the best cut-off range for remission. CONCLUSIONS: in our clinical practice, serum levels of infliximab in Crohn's disease patients should be higher than 4 ug/ml to achieve clinical remission
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