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Psoríase; novas abordagens terapêuticas
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A psoríase é uma doença inflamatória crónica, não contagiosa, que afeta 2 a 3% da população mundial. É de natureza autoimune, o que significa que surge quando o sistema imunitário emite sinais de hiperproliferação das células da pele e, consequentemente, ocorre inflamação que resulta em placas com prurido ou dor, escamas e inflamação em qualquer parte do corpo. Embora a sua origem não esteja totalmente esclarecida, a genética e os fatores ambientais parecem ter papéis importantes para esta alteração do sistema imunitário. Recentemente, o mecanismo fisiopatológico foi esclarecido substancialmente, sendo demonstrado que as células Th17 desempenham um papel fundamental, o que se traduziu numa evolução da terapêutica da psoríase. Existem cinco tipos de psoríase que diferem na localização e características das lesões. Para além disto, estudos recentes sugerem que apresentam diferentes perfis genéticos, o que poderá influenciar a abordagem terapêutica. Atualmente, ainda não existe uma cura definitiva para a psoríase, mas sim um conjunto variado de tratamentos, cujo uso isolado ou em associação permite controlar os sintomas. Sendo assim, os objetivos da terapêutica para esta doença são: controlar rapidamente a doença, diminuir a BSA (área de superfície corporal), diminuir o prurido, a descamação e a espessura das lesões, manter o doente em remissão a longo prazo e evitar recaída, evitar efeitos adversos e, assim, melhorar a qualidade de vida do doente. O tratamento é escolhido tendo por base a gravidade da doença, comorbilidades relevantes, preferência, eficácia e avaliação da resposta individual do doente. As terapêuticas disponíveis para a psoríase são tópicas, fototerapia e sistémicas. Estas últimas incluem fármacos imunossupressores, como o metotrexato e a ciclosporina e agentes biológicos. Os recentes avanços no conhecimento do mecanismo fisiopatológico da doença permitiram o desenvolvimento de novas terapêuticas, principalmente biológicas. Esta representa a área em que se verificam os progressos mais recentes, devido à multiplicidade de alvos terapêuticos descobertos, tais como TNF-alfa, IL-17A, IL-12 e IL23, o que resultou no desenvolvimento de múltiplos anticorpos monoclonais, tendo como alvo estes mediadores chave da cascata inflamatória envolvida na psoríase, o que torna esta terapêutica altamente direcionada e especializada. No entanto, é cara, a via de administração não é a mais cómoda e pode ocorrer uma diminuição da eficácia ao longo do tratamento. Por esta razão é importante o desenvolvimento de pequenas moléculas cuja administração seja via oral, a produção seja menos dispendiosa e que sejam potencialmente tão eficazes como as biológicas. Além disto, a introdução de agentes biossimilares no mercado e a sua melhor acessibilidade financeira, poderá alterar, ainda mais, o tratamento da psoríase.
Psoriasis is a non-contagious chronic inflammatory disease that affects 2-3% of the worldwide population. It is autoimmune, which means that it arises when the immune system emits signals of hyperproliferation of the skin cells and, consequently, the inflammation results in plaque with itching or pain, scaly and inflamed in any part of the body. Although the etiology of the disease is unclear, genetic and environmental factors appear to play important roles in this alteration of the immune system. Recently, the pathophysiological mechanism has been substantially clarified, with Th17 cells play a fundamental role, which has resulted in an evolution of psoriasis therapy. There are five types of psoriasis, which differ in the location and characteristics of the lesions. In addition, recent studies suggest that they have different genetic profiles, which may influence the therapeutic approach. Currently, there is no definitive cure for psoriasis, but a varied set of treatments, the use of which alone or in combination allows to control the symptoms. Thus, the goals of therapy for this disease are rapidly control of the disease, decrease BSA (body surface area), reduce itching, peeling and thickness of lesions, keep the patient in long-term remission and avoid relapse and adverse effects and thus improve the patient's quality of life. Treatment is chosen based on disease severity, relevant comorbidities, preference, efficacy, and assessment of individual patient response. The available therapies for psoriasis are topical, phototherapy and systemic. Systemic therapy are immunosuppressive drugs such as methotrexate, cyclosporine, apremilast and biological agents. Recent advances in the knowledge of the pathophysiological mechanism of the disease have allowed the development of new therapies, mainly biological ones. This represents the area where the most recent progress has been made due to the multiplicity of discovered therapeutic targets such as TNF-alpha, IL-17A, IL-12 and IL-23, which has resulted in the development of multiple monoclonal antibodies. These key mediators target the inflammatory cascade involved in psoriasis, which makes this therapy highly targeted and specialized. However, it is expensive, the route of administration is not the most convenient and a decrease in efficacy may occur throughout treatment. For this reason, it is important to develop small molecules that are administered orally and which are less expensive to produce, although they are not as effective as biological ones. In addition, the introduction of biosimilar agents in the market and their improved financial accessibility may further alter the treatment of psoriasis.
Psoriasis is a non-contagious chronic inflammatory disease that affects 2-3% of the worldwide population. It is autoimmune, which means that it arises when the immune system emits signals of hyperproliferation of the skin cells and, consequently, the inflammation results in plaque with itching or pain, scaly and inflamed in any part of the body. Although the etiology of the disease is unclear, genetic and environmental factors appear to play important roles in this alteration of the immune system. Recently, the pathophysiological mechanism has been substantially clarified, with Th17 cells play a fundamental role, which has resulted in an evolution of psoriasis therapy. There are five types of psoriasis, which differ in the location and characteristics of the lesions. In addition, recent studies suggest that they have different genetic profiles, which may influence the therapeutic approach. Currently, there is no definitive cure for psoriasis, but a varied set of treatments, the use of which alone or in combination allows to control the symptoms. Thus, the goals of therapy for this disease are rapidly control of the disease, decrease BSA (body surface area), reduce itching, peeling and thickness of lesions, keep the patient in long-term remission and avoid relapse and adverse effects and thus improve the patient's quality of life. Treatment is chosen based on disease severity, relevant comorbidities, preference, efficacy, and assessment of individual patient response. The available therapies for psoriasis are topical, phototherapy and systemic. Systemic therapy are immunosuppressive drugs such as methotrexate, cyclosporine, apremilast and biological agents. Recent advances in the knowledge of the pathophysiological mechanism of the disease have allowed the development of new therapies, mainly biological ones. This represents the area where the most recent progress has been made due to the multiplicity of discovered therapeutic targets such as TNF-alpha, IL-17A, IL-12 and IL-23, which has resulted in the development of multiple monoclonal antibodies. These key mediators target the inflammatory cascade involved in psoriasis, which makes this therapy highly targeted and specialized. However, it is expensive, the route of administration is not the most convenient and a decrease in efficacy may occur throughout treatment. For this reason, it is important to develop small molecules that are administered orally and which are less expensive to produce, although they are not as effective as biological ones. In addition, the introduction of biosimilar agents in the market and their improved financial accessibility may further alter the treatment of psoriasis.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019
Palavras-chave
Psoríase Novas terapêuticas Agentes biológicos Sistema imunitário Citocinas Mestrado Integrado - 2019