Publicação
Drug induced liver injury associated with TNF-α inhibitors – infliximab, adalimumab and etanercept: the role of the laboratory
| Resumo: | Background: Knowing and understanding safety profile of a pharmacological product is a continuous process since preclinical toxicological studies to postmarketing clinical evaluation. Although very uncommon, drug-induced liver injury (DILI) leads to drug discontinuation and withdrawn. Biologic therapies such as monoclonal antibodies and fusion proteins have revolutionized the treatment of several diseases. Thus, the main goals of this work was to review clinical reported hepatotoxic events associated with a biologic antirheumatic therapy ( infliximab, etanercept and adalimumab) and to access the importance of the laboratory monitoring in the diagnosis of a drug-induced liver injury. Methods: It was performed a systematic literature revision through analysis of scientific papers and reports, obtained from online databases and websites during the period of April to September 2016. Discussion/Conclusion: The mechanism of drug-induced liver injury is complex and not fully understood. The most common presentation of the hepatotoxicity induced by TNF-α antagonists is an autoimmune phenotype with marked hepatocellular injury, cholestasis can also occurs. After drug discontinuation and corticosteroid therapy, the outcome is positive and progression to severe liver injury is rare. Adverse hepatic events in patients on TNF-α antagonists are lower when comparing with non-biologic disease-modifying antirheumatic drugs. The clinical diagnosis and prediction of DILI is a challenge due to the lack of reliable screening methods, including laboratory markers, and diagnostic standards. In the future, better understanding of the underlying mechanisms of DILI in this group of drugs and identification of genetic or other markers of the hepatotoxicity associated with TNF-α antagonists are imperative for the development of improved preclinical screening assays to be used during clinical trials to evaluate a drug’s potential hepatotoxic effects before its release into the market. |
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| Autores principais: | Santos, Joana Sofia Ligeiro |
| Assunto: | DILI TNF-α antagonist Hepatotoxicity Drug hepatotoxicity Infliximab Etanercept Adalimumab Mestrado Integrado - 2016 |
| Ano: | 2016 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Background: Knowing and understanding safety profile of a pharmacological product is a continuous process since preclinical toxicological studies to postmarketing clinical evaluation. Although very uncommon, drug-induced liver injury (DILI) leads to drug discontinuation and withdrawn. Biologic therapies such as monoclonal antibodies and fusion proteins have revolutionized the treatment of several diseases. Thus, the main goals of this work was to review clinical reported hepatotoxic events associated with a biologic antirheumatic therapy ( infliximab, etanercept and adalimumab) and to access the importance of the laboratory monitoring in the diagnosis of a drug-induced liver injury. Methods: It was performed a systematic literature revision through analysis of scientific papers and reports, obtained from online databases and websites during the period of April to September 2016. Discussion/Conclusion: The mechanism of drug-induced liver injury is complex and not fully understood. The most common presentation of the hepatotoxicity induced by TNF-α antagonists is an autoimmune phenotype with marked hepatocellular injury, cholestasis can also occurs. After drug discontinuation and corticosteroid therapy, the outcome is positive and progression to severe liver injury is rare. Adverse hepatic events in patients on TNF-α antagonists are lower when comparing with non-biologic disease-modifying antirheumatic drugs. The clinical diagnosis and prediction of DILI is a challenge due to the lack of reliable screening methods, including laboratory markers, and diagnostic standards. In the future, better understanding of the underlying mechanisms of DILI in this group of drugs and identification of genetic or other markers of the hepatotoxicity associated with TNF-α antagonists are imperative for the development of improved preclinical screening assays to be used during clinical trials to evaluate a drug’s potential hepatotoxic effects before its release into the market. |
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