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Medicinas Complementares
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Eur J Pharm Sci ; 102: 35-45, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28188909

RESUMO

Infliximab is therapeutic monoclonal antibody (mAb) against TNF-α employed in the treatment of immunoinflammatory diseases. The development of biosimilar mAbs is a global strategy to increase drug accessibility and reduce therapy-associated costs. Herein we compared key physicochemical characteristics and biological activities produced by infliximab and infliximab-Probiomed in order to identify functionally relevant differences between the mAbs. Binding of infliximab-Probiomed to TNF-α was specific and had kinetics comparable to that of the reference product. Both mAbs had highly similar neutralizing efficacy in HUVEC cell cultures stimulated with TNF-α. In vitro induction of CDC and ADCC were also similar between the evaluated products. In vivo comparability was assessed using a transgenic mouse model of arthritis that expresses human TNF-α in a 13-week multiple-administration study. Infliximab and infliximab-Probiomed showed comparable efficacy, safety, and pharmacokinetic profiles. Our results indicate that infliximab-Probiomed has highly similar activities to infliximab in preclinical models, warranting a clinical evaluation of its biosimilarity.


Assuntos
Antirreumáticos , Medicamentos Biossimilares , Infliximab , Animais , Antirreumáticos/farmacocinética , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite/tratamento farmacológico , Artrite/metabolismo , Medicamentos Biossimilares/farmacocinética , Medicamentos Biossimilares/farmacologia , Medicamentos Biossimilares/uso terapêutico , Células CHO , Células Cultivadas , Cricetulus , Citocinas/genética , Citocinas/metabolismo , Selectina E/metabolismo , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Infliximab/farmacocinética , Infliximab/farmacologia , Infliximab/uso terapêutico , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Molécula 1 de Adesão de Célula Vascular/metabolismo
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