PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update

PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update

Reinhard ReussDepartment of Neurology, BKH Bayreuth, Bayreuth, GermanyAbstract: Current standard immunomodulatory therapy with interferons (IFNs) for relapsing–remitting multiple sclerosis (MS) exhibits proven, but limited, efficacy and increased side effects due to the need of frequent ap...

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Autor principal: Reuss R
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2013
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Medicine (General)
R5-920
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spelling oai:doaj.org-article:2f25c22240904349a17b83337b13b9652021-12-02T02:40:42ZPEGylated interferon beta-1a in the treatment of multiple sclerosis – an update1177-54751177-5491https://doaj.org/article/2f25c22240904349a17b83337b13b9652013-05-01T00:00:00Zhttp://www.dovepress.com/pegylated-interferon-beta-1a-in-the-treatment-of-multiple-sclerosis-nd-a13194https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Reinhard ReussDepartment of Neurology, BKH Bayreuth, Bayreuth, GermanyAbstract: Current standard immunomodulatory therapy with interferons (IFNs) for relapsing–remitting multiple sclerosis (MS) exhibits proven, but limited, efficacy and increased side effects due to the need of frequent application of the drug. Therefore, there is a need for more effective and tolerable drugs. Due to their small size, optimization of therapy with IFNs in MS by PEGylation is feasible. PEGylation of an IFN means that at least one molecule of polyethylene glycol (PEG) is covalently added. This modification is a standard procedure to increase the stability, solubility, half-life, and efficacy of a drug, and is applied in several drugs and diseases. Currently, a therapy regimen applying PEG-IFN beta-1a in MS is being developed to achieve an optimized relationship between therapy-related side effects and pharmacokinetic/pharmacodynamic efficacy. Phase I studies demonstrated that subcutaneous PEG-IFN beta-1a at a dose of 125 µg every 2 or 4 weeks might be at least as efficient and safe as the current standard therapy with IFN beta-1a. A global Phase III clinical study is investigating the efficacy of PEG-IFN beta-1a in terms of reduction of the relapse rate in relapsing–remitting MS patients. The latest primary safety and efficacy analysis after 1 year has revealed a favorable risk–benefit profile with no significant difference between dosing regimens. Compared to placebo, the annualized relapse rate was reduced by about one-third and new or newly enlarging T2 brain lesions were reduced by about one-third when dosing every 4 weeks or by two-thirds when dosing every 2 weeks. This presents a significant effect of the dosing interval, favoring administration every 2 weeks. Chronic administration of PEGylated proteins mostly at toxic concentrations causes vacuolation of renal epithelium in animals, which – along with the issue of occurrence of anti-PEG antibodies – has to be addressed by Phase IV studies.Keywords: PEGylation, relapsing–remitting, side effect, Avonex®, ADVANCE, clinical studyReuss RDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2013, Iss default, Pp 131-138 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Reuss R
PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update
description Reinhard ReussDepartment of Neurology, BKH Bayreuth, Bayreuth, GermanyAbstract: Current standard immunomodulatory therapy with interferons (IFNs) for relapsing–remitting multiple sclerosis (MS) exhibits proven, but limited, efficacy and increased side effects due to the need of frequent application of the drug. Therefore, there is a need for more effective and tolerable drugs. Due to their small size, optimization of therapy with IFNs in MS by PEGylation is feasible. PEGylation of an IFN means that at least one molecule of polyethylene glycol (PEG) is covalently added. This modification is a standard procedure to increase the stability, solubility, half-life, and efficacy of a drug, and is applied in several drugs and diseases. Currently, a therapy regimen applying PEG-IFN beta-1a in MS is being developed to achieve an optimized relationship between therapy-related side effects and pharmacokinetic/pharmacodynamic efficacy. Phase I studies demonstrated that subcutaneous PEG-IFN beta-1a at a dose of 125 µg every 2 or 4 weeks might be at least as efficient and safe as the current standard therapy with IFN beta-1a. A global Phase III clinical study is investigating the efficacy of PEG-IFN beta-1a in terms of reduction of the relapse rate in relapsing–remitting MS patients. The latest primary safety and efficacy analysis after 1 year has revealed a favorable risk–benefit profile with no significant difference between dosing regimens. Compared to placebo, the annualized relapse rate was reduced by about one-third and new or newly enlarging T2 brain lesions were reduced by about one-third when dosing every 4 weeks or by two-thirds when dosing every 2 weeks. This presents a significant effect of the dosing interval, favoring administration every 2 weeks. Chronic administration of PEGylated proteins mostly at toxic concentrations causes vacuolation of renal epithelium in animals, which – along with the issue of occurrence of anti-PEG antibodies – has to be addressed by Phase IV studies.Keywords: PEGylation, relapsing–remitting, side effect, Avonex®, ADVANCE, clinical study
format article
author Reuss R
author_facet Reuss R
author_sort Reuss R
title PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update
title_short PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update
title_full PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update
title_fullStr PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update
title_full_unstemmed PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update
title_sort pegylated interferon beta-1a in the treatment of multiple sclerosis – an update
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/2f25c22240904349a17b83337b13b965
work_keys_str_mv AT reussr pegylatedinterferonbeta1ainthetreatmentofmultiplesclerosisndashanupdate
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