Evaluation of the impact of neutralizing antibodies on IFNβ response

Clinica Chimica Acta; International Journal of Clinical Chemistry
A Bertolotto

Abstract

IFNβ therapeutic action depends on a sequence of biological steps: i) the interaction between interferon beta (IFNβ) and its receptor (IFNAR) located at the cell surface of peripheral blood mononuclear cells; ii) activation of second messengers; iii) transcription of several genes containing specific ISRE regions (Interferon Stimulated Response Elements); and iv) synthesis of specific proteins. Although IFNβ therapy has improved treatment options of patients with multiple sclerosis (MS), the long-term efficacy of IFNβs can be compromised due to the development of neutralizing antibodies (NAbs). High titer NAbs develop in about 15% of patients; they abolish IFNβ biological activity and consequently the therapeutic action of IFNβ. Different IFNβ preparations carry different risks of developing NAbs, ranging from 3 to 28%. The risk of inducing NAbs must be considered in the selection of treatment. Guidelines for NAbs testing and the therapeutic decision in case of NAbs positivity have been established. NAbs positivity predicts MRI and clinical activity. Precocious identification of Nabs-positive patients and switch to alternative treatments can improve the percentage of responders and allow a better allocation of relevant economic...Continue Reading

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Citations

Sep 28, 2015·Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research·Felicity AllenNicholas Adlard
Apr 12, 2016·Proteomics. Clinical Applications·Piero Del BoccioDamiana Pieragostino
Apr 15, 2017·Clinical Pharmacology in Drug Development·Lanfranco PellesiLuigi Alberto Pini
Apr 8, 2017·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Arezou SayadMohammad Taheri
Mar 23, 2017·Therapeutic Drug Monitoring·Marzia CaldanoAntonio Bertolotto
Mar 16, 2017·Brain and Behavior·Jana LibertinovaMartin Bojar
Dec 6, 2016·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Michael AuerFlorian Deisenhammer
Nov 12, 2015·BMC Medicine·Dimos D Mitsikostas, Alan M Rapoport

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