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Curr Opin Pharmacol ; 54: 59-71, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32942096

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease that is associated with chronic inflammation in joints, which contribute to synovial membrane hyperplasia and cartilage damage. Conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX) and leflunomide (LEF), are the common RA therapy to reduce inflammation and disease progression. Recently, drug-resistance in RA with conventional treatment has become an issue. Mutations in p53 tumor suppressor gene and overexpression of ABCB1/MDR-1/P-gp transporters may contribute to antirheumatic drug-resistance in RA. Biologic DMARDs (bDMARDs) are often prescribed, when conventional DMARDs fail to treat RA, by targeting proinflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. The efficacy of bDMARDs is affected by personal factors, for example, age, smoking, body mass index (BMI), immunogenicity, and genetic polymorphisms. This review highlights the role of p53 gene mutations, ABC family transporters and personal factors in antirheumatic drug-resistance, which may lead to new personalized therapies against RA with an increased drug-sensitivity.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Resistência a Medicamentos , Genes p53 , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Resistência a Medicamentos/genética , Humanos , Mutação
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