Cargando…
PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update
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....
Autor principal: | |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686537/ https://www.ncbi.nlm.nih.gov/pubmed/23807836 http://dx.doi.org/10.2147/BTT.S29948 |
_version_ | 1782273792631898112 |
---|---|
author | Reuss, Reinhard |
author_facet | Reuss, Reinhard |
author_sort | Reuss, Reinhard |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3686537 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-36865372013-06-27 PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update Reuss, Reinhard Biologics Review 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. Dove Medical Press 2013 2013-05-29 /pmc/articles/PMC3686537/ /pubmed/23807836 http://dx.doi.org/10.2147/BTT.S29948 Text en © 2013 Reuss, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Review Reuss, Reinhard PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update |
title | 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_short | 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 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686537/ https://www.ncbi.nlm.nih.gov/pubmed/23807836 http://dx.doi.org/10.2147/BTT.S29948 |
work_keys_str_mv | AT reussreinhard pegylatedinterferonbeta1ainthetreatmentofmultiplesclerosisanupdate |