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Real-World Lab Data in Natalizumab Treated Multiple Sclerosis Patients Up to 6 Years Long-Term Follow Up

Natalizumab inhibits the transmigration of immune cells across the blood-brain barrier thus inhibiting inflammation in the central nervous system. Generally, this blockade at the blood-brain barrier has significant influence on the circulating lymphocytes. Up to date, only short-term data on periphe...

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Autores principales: Kaufmann, Maxi, Haase, Rocco, Proschmann, Undine, Ziemssen, Tjalf, Akgün, Katja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292961/
https://www.ncbi.nlm.nih.gov/pubmed/30581413
http://dx.doi.org/10.3389/fneur.2018.01071
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author Kaufmann, Maxi
Haase, Rocco
Proschmann, Undine
Ziemssen, Tjalf
Akgün, Katja
author_facet Kaufmann, Maxi
Haase, Rocco
Proschmann, Undine
Ziemssen, Tjalf
Akgün, Katja
author_sort Kaufmann, Maxi
collection PubMed
description Natalizumab inhibits the transmigration of immune cells across the blood-brain barrier thus inhibiting inflammation in the central nervous system. Generally, this blockade at the blood-brain barrier has significant influence on the circulating lymphocytes. Up to date, only short-term data on peripheral blood parameters are available which are mostly from controlled clinical trials and not from real-world experience. Real-world lab data of 120 patients diagnosed with highly active disease course of relapsing-remitting multiple sclerosis (RRMS) were analyzed during natalizumab treatment. Patient sampling was performed by consecutive recruitment in the Multiple Sclerosis Center Dresden. Lab testing was performed before and at every third infusion up to 72 months follow-up. After first natalizumab infusion, absolute numbers of all major lymphocyte populations including CD4+ T-cells, CD8+ T-cells, CD19+ B-cells, and NK-cells significantly increased and remained stable during the whole observation period of 72 months. Upon lymphocyte subsets, CD19+ B-cells presented a disproportionate increase up to levels higher than normal level in most of the treated patients. Neutralizing antibodies to natalizumab abrogated the described changes. Intra-individual variation of lymphocytes and its subsets remained in a narrow range for the whole treatment period. CD4/CD8 ratio did not change compared to baseline measurement up to 6 years of natalizumab treatment. Monocytes, eosinophils, and basophils, but not neutrophils persistently increased during natalizumab treatment. Hematological parameters including erythrocyte, platelet count, hemoglobin, and hematocrit remained unchanged compared to baseline. Interestingly, immature precursor cells including erythroblasts were detectable in 36,8% of the treated patients during natalizumab therapy, but not in the pretreatment period. Asymptomatic elevations of liver enzymes were rare, mostly only transient and lower than 3x upper normal limit. Kidney function parameters remained stable within physiological ranges in most patients. CRP levels >20 mg/dl were recognized only in 10 patients during natalizumab therapy and were mostly linked to respiratory tract infections. In our present analysis, we report persistent, but stable increases of peripheral immune cell subtypes in natalizumab treated patients. Additional serological analyses confirm excellent tolerability and safety even 6 years after natalizumab initiation in post-marketing experience.
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spelling pubmed-62929612018-12-21 Real-World Lab Data in Natalizumab Treated Multiple Sclerosis Patients Up to 6 Years Long-Term Follow Up Kaufmann, Maxi Haase, Rocco Proschmann, Undine Ziemssen, Tjalf Akgün, Katja Front Neurol Neurology Natalizumab inhibits the transmigration of immune cells across the blood-brain barrier thus inhibiting inflammation in the central nervous system. Generally, this blockade at the blood-brain barrier has significant influence on the circulating lymphocytes. Up to date, only short-term data on peripheral blood parameters are available which are mostly from controlled clinical trials and not from real-world experience. Real-world lab data of 120 patients diagnosed with highly active disease course of relapsing-remitting multiple sclerosis (RRMS) were analyzed during natalizumab treatment. Patient sampling was performed by consecutive recruitment in the Multiple Sclerosis Center Dresden. Lab testing was performed before and at every third infusion up to 72 months follow-up. After first natalizumab infusion, absolute numbers of all major lymphocyte populations including CD4+ T-cells, CD8+ T-cells, CD19+ B-cells, and NK-cells significantly increased and remained stable during the whole observation period of 72 months. Upon lymphocyte subsets, CD19+ B-cells presented a disproportionate increase up to levels higher than normal level in most of the treated patients. Neutralizing antibodies to natalizumab abrogated the described changes. Intra-individual variation of lymphocytes and its subsets remained in a narrow range for the whole treatment period. CD4/CD8 ratio did not change compared to baseline measurement up to 6 years of natalizumab treatment. Monocytes, eosinophils, and basophils, but not neutrophils persistently increased during natalizumab treatment. Hematological parameters including erythrocyte, platelet count, hemoglobin, and hematocrit remained unchanged compared to baseline. Interestingly, immature precursor cells including erythroblasts were detectable in 36,8% of the treated patients during natalizumab therapy, but not in the pretreatment period. Asymptomatic elevations of liver enzymes were rare, mostly only transient and lower than 3x upper normal limit. Kidney function parameters remained stable within physiological ranges in most patients. CRP levels >20 mg/dl were recognized only in 10 patients during natalizumab therapy and were mostly linked to respiratory tract infections. In our present analysis, we report persistent, but stable increases of peripheral immune cell subtypes in natalizumab treated patients. Additional serological analyses confirm excellent tolerability and safety even 6 years after natalizumab initiation in post-marketing experience. Frontiers Media S.A. 2018-12-07 /pmc/articles/PMC6292961/ /pubmed/30581413 http://dx.doi.org/10.3389/fneur.2018.01071 Text en Copyright © 2018 Kaufmann, Haase, Proschmann, Ziemssen and Akgün. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Kaufmann, Maxi
Haase, Rocco
Proschmann, Undine
Ziemssen, Tjalf
Akgün, Katja
Real-World Lab Data in Natalizumab Treated Multiple Sclerosis Patients Up to 6 Years Long-Term Follow Up
title Real-World Lab Data in Natalizumab Treated Multiple Sclerosis Patients Up to 6 Years Long-Term Follow Up
title_full Real-World Lab Data in Natalizumab Treated Multiple Sclerosis Patients Up to 6 Years Long-Term Follow Up
title_fullStr Real-World Lab Data in Natalizumab Treated Multiple Sclerosis Patients Up to 6 Years Long-Term Follow Up
title_full_unstemmed Real-World Lab Data in Natalizumab Treated Multiple Sclerosis Patients Up to 6 Years Long-Term Follow Up
title_short Real-World Lab Data in Natalizumab Treated Multiple Sclerosis Patients Up to 6 Years Long-Term Follow Up
title_sort real-world lab data in natalizumab treated multiple sclerosis patients up to 6 years long-term follow up
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292961/
https://www.ncbi.nlm.nih.gov/pubmed/30581413
http://dx.doi.org/10.3389/fneur.2018.01071
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