Vedolizumabe: uso de anticorpo monoclonal humanizado na Doença Inflamatória Intestinal (DII)
Data
2023-06-26
Autores
Melo, Caroline Miranda 
Orientadores
Fernandes, Liliam
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A doença inflamatória intestinal (DII) representa um grupo de doenças crônicas, idiopáticas de patogênese não totalmente conhecida. Fatores genéticos, ambientais, interações anormais com a flora bacteriana intestinal e alterações na permeabilidade da parede intestinal desempenham papéis variáveis no fenômeno de descontrole imunológico observado nessas situações, levando a diferentes graus de lesão. A doença de Crohn e a colite ulcerativa compartilham a maioria das características epidemiológicas da DII. No Brasil, estima-se que a prevalência da DII seja de 30,2 por 100.000 indivíduos. É provável que as DIIs apresentem múltiplas causas, envolvendo uma interação entre suscetibilidade geneticamente mediada, fatores ambientais e função imunológica. Embora a DII não tenha uma causa definida, os estudos abrangentes realizados neste respeito destacam o papel da genética e do ambiente como principais fatores. Este trabalho tem como objetivo explicar a importância do tratamento da DII moderada à grave com anticorpos monoclonais, apresentar e discutir as diferenças farmacocinéticas e farmacodinâmicas dos medicamentos imunobiológicos, a fim de compreender quais serão os impactos que essas propriedades terão no manejo da doença, evidenciando o controle e a remissão dos sintomas advindos do quadro clínico nos pacientes e elucidando a importância da doença inflamatória intestinal no âmbito da saúde no Brasil e do mundo. Nos últimos anos, os anticorpos anti-TNFα são os fármacos mais usados após falhas de corticoides, antibióticos e imunossupressores, ou como primeira linha em pacientes de alto risco (doença fistulizante e extensa). Porém, pelo fato de apresentar limitações em alguns pacientes durante o tratamento, novas drogas com mecanismo de ação diferenciado, eficazes, com maior seletividade e ganhos de segurança, vêm agregar de forma decisiva opções ao tratamento biológico das DIIs. O vedolizumabe é um medicamento biológico imunossupressor seletivo para o intestino. É um anticorpo monoclonal humanizado que se liga especificamente à integrina α4β7, a qual é expressada, de preferência, em linfócitos T auxiliares (T helper) alojados no intestino. Ao se ligar à integrina α4β7 em determinados linfócitos, o vedolizumabe inibe a adesão destas células à molécula-1 de adesão da célula de adressina da mucosa (MAdCAM-1), evitando a inflamação. Diante de todos os estudos abordados
neste trabalho e experiências clínicas, percebe-se que o tratamento da DII deve ser feito de maneira individualizada, focando na necessidade do paciente e permitindo que ele faça parte da escolha terapêutica que irá melhor beneficiar a sua qualidade de vida. A partir dos estudos abordados, podemos concluir que o vedolizumabe é um fármaco seguro e eficaz recomendado para uso principalmente em pacientes naive moderado à grave na doença de Crohn e pacientes falhados ou naives moderado à grave na retocolite ulcerativa.
Inflammatory bowel disease represents a group of chronic, idiopathic diseases of unknown pathogenesis. Genetic and environmental factors, abnormal interactions with the intestinal bacterial flora and alterations in the permeability of the intestinal wall play variable roles in the phenomenon of immune imbalance observed in these situations, leading to different degrees of injury. Crohn's disease and ulcerative colitis share most of the epidemiologic features of IBD. In Brazil, it is estimated that the prevalence of IBD is 30.2 per 100,000 individuals. IBD are likely to have multiple causes, involving an interaction between genetically mediated susceptibility, environmental factors, and immune function. Although IBD doesn’t have a defined cause, the extensive studies carried out in this regard highlight the role of genetics and environment as major factors. This work aims to explain the importance of treating moderate to severe IBD with monoclonal antibodies, to present and discuss the pharmacokinetic and pharmacodynamic differences of immunobiological drugs, in order to understand the impacts that these properties will have on the management of the disease, highlighting the control and remission of symptoms arising from the clinical picture in patients and elucidating the importance of inflammatory bowel disease in the context of health in Brazil and worldwide. In recent years, anti-TNFα antibodies have been the drugs most used after failure of corticosteroids, antibiotics, and immunosuppressants, or as first-line therapy in high-risk patients (fistulant and extensive disease). However, due to the fact that it presents limitations in some patients during treatment, new drugs with a differentiated, effective mechanism of action, with greater selectivity and safety gains, come to decisively add options to the biological treatment of IBD. Vedolizumab is a selective immunosuppressive biological drug for the intestine. It is a humanized monoclonal antibody that specifically binds to the α4β7 integrin, which is preferentially expressed in T helper lymphocytes (T helper) housed in the intestine. By binding to the α4β7 integrin on certain lymphocytes, vedolizumab inhibits the adhesion of these cells to mucosal cell addressin adhesion molecule-1 (MAdCAM-1), preventing inflammation. In view of all the studies discussed in this work and clinical experiences, it is clear that the treatment of IBD must be done on an individual basis, focusing on the patient's needs and allowing him to be part of the therapeutic choice that will best benefit his quality of life. From the studies discussed, we can conclude that vedolizumab is a safe and effective drug recommended for use mainly in patients naive moderate to severe in Crohn's disease and patients failed or naive moderately to severe in ulcerative colitis.
Inflammatory bowel disease represents a group of chronic, idiopathic diseases of unknown pathogenesis. Genetic and environmental factors, abnormal interactions with the intestinal bacterial flora and alterations in the permeability of the intestinal wall play variable roles in the phenomenon of immune imbalance observed in these situations, leading to different degrees of injury. Crohn's disease and ulcerative colitis share most of the epidemiologic features of IBD. In Brazil, it is estimated that the prevalence of IBD is 30.2 per 100,000 individuals. IBD are likely to have multiple causes, involving an interaction between genetically mediated susceptibility, environmental factors, and immune function. Although IBD doesn’t have a defined cause, the extensive studies carried out in this regard highlight the role of genetics and environment as major factors. This work aims to explain the importance of treating moderate to severe IBD with monoclonal antibodies, to present and discuss the pharmacokinetic and pharmacodynamic differences of immunobiological drugs, in order to understand the impacts that these properties will have on the management of the disease, highlighting the control and remission of symptoms arising from the clinical picture in patients and elucidating the importance of inflammatory bowel disease in the context of health in Brazil and worldwide. In recent years, anti-TNFα antibodies have been the drugs most used after failure of corticosteroids, antibiotics, and immunosuppressants, or as first-line therapy in high-risk patients (fistulant and extensive disease). However, due to the fact that it presents limitations in some patients during treatment, new drugs with a differentiated, effective mechanism of action, with greater selectivity and safety gains, come to decisively add options to the biological treatment of IBD. Vedolizumab is a selective immunosuppressive biological drug for the intestine. It is a humanized monoclonal antibody that specifically binds to the α4β7 integrin, which is preferentially expressed in T helper lymphocytes (T helper) housed in the intestine. By binding to the α4β7 integrin on certain lymphocytes, vedolizumab inhibits the adhesion of these cells to mucosal cell addressin adhesion molecule-1 (MAdCAM-1), preventing inflammation. In view of all the studies discussed in this work and clinical experiences, it is clear that the treatment of IBD must be done on an individual basis, focusing on the patient's needs and allowing him to be part of the therapeutic choice that will best benefit his quality of life. From the studies discussed, we can conclude that vedolizumab is a safe and effective drug recommended for use mainly in patients naive moderate to severe in Crohn's disease and patients failed or naive moderately to severe in ulcerative colitis.