RESUMO
BACKGROUND AND OBJECTIVES: The incidence of inflammatory bowel disease (IBD) in Spain has been traditionally lower than in Northern European countries. Recent epidemiological studies have found that these differences are diminishing. This study estimates the incidence of IBD in Málaga (Spain), a city in Southern Spain and relates its results to those found in our neighboring countries. MATERIAL AND METHODS: This was a prospective study designed to collect new cases diagnosed during the period from 2007-2008 and follow up these patients. Incidence is expressed as number of patients per 100,000 population per year. The population distribution found in the European Collaborative Study was used to standardize incidence rates. RESULTS: The gross incidence rate of IBD in Málaga is 9/105, the standardized incidence rate is 12.3/105 (9.7-15.6). CONCLUSIONS: These data are similar to those found in our surroundings, although a higher incidence rate for Crohn's disease (CD) as compared to ulcerative colitis (UC) was found. The clinical characteristics and outcomes of our patients do not differ significantly from those described for other populations.
Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Adulto , Fatores Etários , Estudos de Coortes , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologiaRESUMO
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.
RESUMO
Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn's disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPRmt) upon treatment with ibuprofen. Finally, colon biopsies from Crohn's disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPRmt, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPRmt pathway in the pathophysiology of Crohn's disease.
RESUMO
BACKGROUND: The ideal length of treatment with thiopurines in patients with ulcerative colitis (UC) in sustained remission remains unknown. It is widely accepted that the drug withdrawal is associated with a worse outcome. The aim of this study was to analyze the outcome after this withdrawal and to identify predictors of relapse. METHODS: A multicenter and retrospective study was designed. A total of 102 patients with UC who discontinued thiopurines in a situation of sustained remission were included. All the patients were followed up until last revision or until relapse (understood as the occurrence of signs and symptoms of UC that required a rescue treatment). RESULTS: After thiopurines withdrawal, overall relapse was recorded in 32.35% of the patients: 18.88% in the first year, 36.48% in the third, and 43.04% in the fifth year after withdrawal. On multivariate analysis, predictors of relapse were the time from diagnosis of UC until the starting of thiopurines (hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.01-1.02; P = 0.039), the number of relapses before the withdrawal (HR, 1.3; 95% CI, 1.01-1.66; P = 0.029), pancolitis (HR, 5.01; 95% CI, 1.95-26.43; P = 0.028), the duration of treatment with thiopurines (HR, 0.15; 95% CI, 0.03-0.66; P = 0.013) and the situation of biological remission at withdrawal (HR, 0.004; 95% CI, 0.0001-0.14; P = 0.002). CONCLUSIONS: The withdrawal of thiopurines in patients with UC, although in sustained remission, is related to a high relapse rate. Clinical variables such as the extent of the disease, the duration of treatment or time from diagnosis to the start of thiopurines should be considered before stopping these drugs.
Assuntos
Azatioprina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Mercaptopurina/uso terapêutico , Adulto , Idoso , Colite Ulcerativa/diagnóstico , Colonoscopia , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Suspensão de TratamentoRESUMO
Introducción y objetivos: la incidencia de enfermedad inflamatoria intestinal (EII) en España ha sido clásicamente inferior a la incidencia de los países del norte de Europa. Estudios epidemiológicos recientes muestran que la brecha está disminuyendo. Este estudio estima la incidencia de EII en Málaga, una ciudad en el sur de España, y relaciona dichas cifras con los datos de nuestro entorno. Material y métodos: este es un estudio prospectivo que fue diseñado para recoger los nuevos casos diagnosticados durante los años 2007-2008, y para realizar el seguimiento de estos pacientes. La incidencia se expresa como el número de pacientes por cada 100.000 habitantes por año. La distribución de la población del estudio colaborativo europeo se utilizó para normalizar la tasa de incidencia. Resultados: la incidencia bruta de la EII en Málaga es 9/105, la incidencia estandarizada es de 12,3/105 (9,7-15,6). Conclusiones: estos datos son similares a los de nuestro medio ambiente, aunque se observa una mayor incidencia para la enfermedad de Crohn (EC) que para la colitis ulcerosa (CU). Las características clínicas y evolución de nuestro paciente no presentan grandes diferencias con respecto a lo descrito en otras poblaciones (AU)
Background and objectives: The incidence of inflammatory bowel disease (IBD) in Spain has been traditionally lower than in Northern European countries. Recent epidemiological studies have found that these differences are diminishing. This study estimates the incidence of IBD in Málaga (Spain), a city in Southern Spain and relates its results to those found in our neighboring countries. Material and methods: This was a prospective study designed to collect new cases diagnosed during the period from 2007-2008 and follow up these patients. Incidence is expressed as number of patients per 100,000 population per year. The population distribution found in the European Collaborative Study was used to standardize incidence rates. Results: The gross incidence rate of IBD in Málaga is 9/105, the standardized incidence rate is 12.3/105 (9.7-15.6). Conclusions: These data are similar to those found in our surroundings, although a higher incidence rate for Crohn's disease (CD) as compared to ulcerative colitis (UC) was found. The clinical characteristics and outcomes of our patients do not differ significantly from those described for other populations (AU)