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In inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), the immune system relentlessly attacks intestinal cells, causing recurrent tissue damage over the lifetime of patients. The etiology of IBD is complex and multifactorial, involving environmental, microbiota, genetic, and immunological factors that alter the molecular basis of the organism. Among these, the microbiota and immune cells play pivotal roles; the microbiota generates antigens recognized by immune cells and antibodies, while autoantibodies target and attack the intestinal membrane, exacerbating inflammation and tissue damage. Given the altered molecular framework, the analysis of multiple molecular biomarkers in patients proves exceedingly valuable for diagnosing and prognosing IBD, including markers like C reactive protein and fecal calprotectin. Upon detection and classification of patients, specific treatments are administered, ranging from conventional drugs to new biological therapies, such as antibodies to neutralize inflammatory molecules like tumor necrosis factor (TNF) and integrin. This review delves into the molecular basis and targets, biomarkers, treatment options, monitoring techniques, and, ultimately, current challenges in IBD management.
Assuntos
Biomarcadores , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/imunologia , AnimaisRESUMO
Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.
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We present the clinical case of a 56-year-old former smoker female, with a family history of maternal ulcerative colitis and personal history of ankylosing spondylitis treated with Ixekizumab for 3 months, who was admitted for fever, left iliac fossa pain and diarrhea without pathological products of 2 weeks of evolution. Abdominopelvic computed tomography scan identified pancolitis. Complete colonoscopy revealed continuous involvement of the proximal colon (right and transverse colon presented deep ulcerations and mucosal friability) with preservation of the terminal ileum. After many complementary tests and according to the clinical context, the diagnosis of extensive colitis associated with IL-17 inhibitor was established.
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Humanos , Feminino , Adulto , Imunodeficiência de Variável Comum/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infliximab/uso terapêutico , Linfócitos B , Linfócitos T , Fator de Necrose Tumoral alfa/uso terapêuticoRESUMO
INTRODUCCIÓN: Infliximab (IFX) es efectivo en la colitis ulcerosa (CU) y en obtener la curación de la mucosa (CM). Se conoce poco el papel que juega la CM en la evolución posterior de la enfermedad y qué ocurre una vez se interrumpe el tratamiento. OBJETIVOS: Conocer las características y evolución de pacientes con CU tratados con IFX, que, tras obtener remisión profunda, suspenden el tratamiento. MÉTODOS: Estudio observacional, prospectivo, de pacientes con CU moderada a grave, corticorresistente/corticodependiente, naïves a anti-TNF. Pauta de administración: IFX: 5mg/kg a 0-2-6 semanas y cada 8 después, hasta semana 54. En los pacientes que alcanzaron la CM, el tratamiento se interrumpió, con seguimiento posterior de al menos 20 meses. Remisión clínica (RC): puntuación Mayo < 2; respuesta clínica: disminución de 3 puntos; CM: puntuación Mayo 0-1. Remisión profunda: paciente con RC y CM. RESULTADOS: De los 21 pacientes incluidos, 19 completaron el estudio (colectomía = 1; no respondedor = 1). Edad media: 47,8 años. CU: grave (n = 13); moderada (n = 6), la mayoría, corticorresistentes (n = 11). Un 57,8% recibieron tratamiento combinado con inmunosupresores y en el 31,5% el tratamiento se intensificó. Semana 54: 16 pacientes (84,2%) presentaron respuesta clínica, 13 (68,4%) RC y 12 (63,2%) remisión profunda. De ellos, 6 (50%) tuvieron un nuevo episodio de CU y 3 (25%) fueron tratados de nuevo con IFX. Estos últimos, en las 12 primeras semanas de la retirada del fármaco y todos respondieron de nuevo. El 91,7% de los pacientes permanecían libres de IFX a las 8 semanas y el 75% a las 12, manteniéndose en esta situación durante el tiempo de seguimiento. Ninguno de los pacientes precisó ingreso ni cirugía durante el seguimiento. CONCLUSIONES: Los pacientes con CU que obtuvieron RM con IFX, tras suspender el tratamiento presentaron nuevo brote en la mitad de los casos y el 25% precisaron tratamiento de nuevo con IFX
INTRODUCTION: Infliximab (IFX) is effective in treating ulcerative colitis (UC) and in achieving mucosal healing (MH). Little is known about the role of mucosal healing (MH) in the subsequent evolution of the disease and the consequences of discontinuing treatment. AIMS: To evaluate the characteristics and evolution of patients with UC treated with IFX who discontinued treatment after disease remission. METHODS: Observational, prospective study of patients with moderate to severe UC, corticosteroid-resistant/corticosteroid-dependent, naïve to anti-TNF. IFX administration regimen: 5 mg/kg at 0-2-6 weeks and every 8 weeks thereafter until week 54. In patients achieving MH, IFX was discontinued and the patients were followed-up for at least 20 months. Clinical remission (CR): mayo score < 2; Clinical response: decrease in mayo score of 3 points; MH: mayo score 0-1; Deep remission: patient with CR and MH. RESULTS: Of the 21 patients enrolled, 19 completed the study (colectomy, n = 1; non-responder, n = 1). Mean age: 47.8 years. UC: severe (n = 13) and moderate (n = 6); most patients (n = 11) were steroid-resistant; 57.8% received combined treatment with immunosuppressants, and 31.5% intensified treatment. Week 54: 16 patients (84.2%) showed clinical response, 13 (68.4%) showed CR, and 12 (63.2%) deep remission. Of these, 6 (25%) presented a new episode of UC, and in 3 (25%) IFX was restarted within 12 weeks of discontinuation, with all patients responding. Of the total sample, 91.7% remained IFX-free at week 8, and 75% at week 12, with no remission during follow-up. None of the patients required hospitalization or surgery. CONCLUSIONS: Half of patients with deep remission of UC with IFX therapy presented a new episode after treatment discontinuation, and in 25% IFX therapy was restarted
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Humanos , Colite Ulcerativa/tratamento farmacológico , Infliximab/uso terapêutico , Suspensão de Tratamento , Indução de Remissão/métodos , Intervalo Livre de Doença , Resultado do Tratamento , Fatores de RiscoRESUMO
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