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Gerir a imunogenicidade em anticorpos terapĂȘuticos
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Resumo(s)
Os anticorpos monoclonais sĂŁo uma terapĂȘutica altamente especĂfica, possuem diminutos efeitos adversos e sĂŁo o foco da pesquisa para tratamento das doenças de carĂĄcter moderado a grave, como as doenças inflamatĂłrias crĂłnicas, destacando a artrite reumatĂłide, as doenças inflamatĂłrias do intestino e a psorĂase. Para o tratamento destas doenças Ă© de destacar o uso de construçÔes de anticorpos que visam o TNFïĄ, nomeadamente o Infliximab e o Adalimumab. Estes fĂĄrmacos podem reduzir drasticamente a actividade da doença e em alguns doentes induzem a sua remissĂŁo total. PorĂ©m nem todos os doentes possuem resposta ao tratamento e se possuĂrem, pode nĂŁo ser favorĂĄvel. Os doentes podem apresentar uma falha na resposta Ă terapĂȘutica, as razĂ”es para essa falha de resposta sĂŁo parcialmente conhecidas, sabe-se que uma das razĂ”es Ă© o surgimento de imunogenicidade. A imunogenicidade existe em medicamentos originais e biossimilares podendo surgir com impactos diferentes. Esta Ă© influenciada por vĂĄrios factores, de destacar os factores relacionados com o produto e com o doente. Uma das facetas da imunogenicidade Ă© a capacidade que os doentes desenvolvam anticorpos anti-fĂĄrmaco (ADAs), que podem ser anticorpos neutralizantes ou nĂŁo neutralizantes, sendo que ambos contribuem para a falha do tratamento. A necessidade de monitorizar os doentes para nĂveis circulantes de fĂĄrmacos anti-TNFïĄ funcionais e de ADAs Ă© extremamente necessĂĄrio para o sucesso do tratamento. O uso de imunossupressores concomitantemente com os mAb, o uso de doses ideais entre outros podem ajudar na optimização da terapĂȘutica do doente. Deve-se manter a adaptação individual da terapĂȘutica ao doente, de modo a atingir padrĂ”es de efectividade e tendo em conta o custo-benefĂcio a longo prazo. Num futuro prĂłximo, o desafio para quem estĂĄ a desenvolver novos fĂĄrmacos biolĂłgicos Ă© tentar minimizar os efeitos da imunogenicidade e o seu impacto no doente.
Monoclonal antibodies are a highly specific therapy, have minor adverse effects and are the focus of research for the treatment of moderate to severe diseases, such as chronic inflammatory diseases, rheumatoid arthritis, inflammatory bowel diseases and psoriasis. For the treatment of these diseases, the use of antibody constructs targeting TNFïĄ should be highlighted, namely Infliximab and Adalimumab. These drugs can drastically reduce disease activity and in some patients induce their complete remission. However, not all patients have a response to treatment and if they do, it may not be favorable. Patients may show a failure in response to therapy, the reasons for this failure to respond are partially known, one of the reasons known to be the emergence of immunogenicity. Immunogenicity exists in original and biossimilars drugs and may arise with different impacts. Immunogenicity is influenced by several factors, the more relevant being related to the product and the patient. One of the facets of immunogenicity consists of the ability of patients to develop anti-drug antibodies (ADAs): they may be neutralizing or non-neutralizing antibodies, both of which contribute to failure of treatment. The need to monitor patients for circulating levels of functional anti-TNF drugs and ADAs is extremely necessary for successful treatment. The use of immunosuppressors concomitantly with mAbs, the use of optimal doses among others, may aid in the optimization of patient therapy. Individual treatment adaptation to the patient should be maintained in order to achieve standards of effectiveness and taking into account long-term cost-benefit. The challenge for anyone developing new biological drugs is to try to minimize the effects of immunogenicity and its impact on the patient in the near future.
Monoclonal antibodies are a highly specific therapy, have minor adverse effects and are the focus of research for the treatment of moderate to severe diseases, such as chronic inflammatory diseases, rheumatoid arthritis, inflammatory bowel diseases and psoriasis. For the treatment of these diseases, the use of antibody constructs targeting TNFïĄ should be highlighted, namely Infliximab and Adalimumab. These drugs can drastically reduce disease activity and in some patients induce their complete remission. However, not all patients have a response to treatment and if they do, it may not be favorable. Patients may show a failure in response to therapy, the reasons for this failure to respond are partially known, one of the reasons known to be the emergence of immunogenicity. Immunogenicity exists in original and biossimilars drugs and may arise with different impacts. Immunogenicity is influenced by several factors, the more relevant being related to the product and the patient. One of the facets of immunogenicity consists of the ability of patients to develop anti-drug antibodies (ADAs): they may be neutralizing or non-neutralizing antibodies, both of which contribute to failure of treatment. The need to monitor patients for circulating levels of functional anti-TNF drugs and ADAs is extremely necessary for successful treatment. The use of immunosuppressors concomitantly with mAbs, the use of optimal doses among others, may aid in the optimization of patient therapy. Individual treatment adaptation to the patient should be maintained in order to achieve standards of effectiveness and taking into account long-term cost-benefit. The challenge for anyone developing new biological drugs is to try to minimize the effects of immunogenicity and its impact on the patient in the near future.
Descrição
Trabalho Final de Mestrado Integrado, CiĂȘncias FarmacĂȘuticas, Universidade de Lisboa, Faculdade de FarmĂĄcia, 2017
Palavras-chave
Anticorpo terapĂȘutico Imunogenicidade Infliximab Adalimumab Mestrado Integrado - 2017