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Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis
BACKGROUND: Recent data from animal models of multiple sclerosis (MS) and from a pilot study indicated a possible beneficial impact of statins on MS. METHODOLOGY/PRINCIPAL FINDINGS: Safety, tolerability and effects on disease activity of atorvastatin given alone or in combination with interferon-bet...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276246/ https://www.ncbi.nlm.nih.gov/pubmed/18398457 http://dx.doi.org/10.1371/journal.pone.0001928 |
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author | Paul, Friedemann Waiczies, Sonia Wuerfel, Jens Bellmann-Strobl, Judith Dörr, Jan Waiczies, Helmar Haertle, Mareile Wernecke, Klaus D. Volk, Hans-Dieter Aktas, Orhan Zipp, Frauke |
author_facet | Paul, Friedemann Waiczies, Sonia Wuerfel, Jens Bellmann-Strobl, Judith Dörr, Jan Waiczies, Helmar Haertle, Mareile Wernecke, Klaus D. Volk, Hans-Dieter Aktas, Orhan Zipp, Frauke |
author_sort | Paul, Friedemann |
collection | PubMed |
description | BACKGROUND: Recent data from animal models of multiple sclerosis (MS) and from a pilot study indicated a possible beneficial impact of statins on MS. METHODOLOGY/PRINCIPAL FINDINGS: Safety, tolerability and effects on disease activity of atorvastatin given alone or in combination with interferon-beta (IFN-β) were assessed in a phase II open-label baseline-to-treatment trial in relapsing-remitting MS (RRMS). Patients with at least one gadolinium-enhancing lesion (CEL) at screening by magnetic resonance imaging (MRI) were eligible for the study. After a baseline period of 3 monthly MRI scans (months −2 to 0), patients followed a 9-month treatment period on 80 mg atorvastatin daily. The number of CEL in treatment months 6 to 9 compared to baseline served as the primary endpoint. Other MRI-based parameters as well as changes in clinical scores and immune responses served as secondary endpoints. Of 80 RRMS patients screened, 41 were included, among them 16 with IFN-β comedication. The high dose of 80 mg atorvastatin was well tolerated in the majority of patients, regardless of IFN-β comedication. Atorvastatin treatment led to a substantial reduction in the number and volume of CEL in two-sided multivariate analysis (p = 0.003 and p = 0.008). A trend towards a significant decrease in number and volume of CEL was also detected in patients with IFN-β comedication (p = 0.060 and p = 0.062), in contrast to patients without IFN-β comedication (p = 0.170 and p = 0.140). Immunological investigations showed no suppression in T cell response but a significant increase in IL-10 production. CONCLUSIONS/SIGNIFICANCE: Our data suggest that high-dose atorvastatin treatment in RRMS is safe and well tolerated. Moreover, MRI analysis indicates a possible beneficial effect of atorvastatin, alone or in combination with IFN-β, on the development of new CEL. Thus, our findings provide a rationale for phase II/III trials, including combination of atorvastatin with already approved immunomodulatory therapy regimens. TRIAL REGISTRATION: ClinicalTrials.gov NCT00616187 |
format | Text |
id | pubmed-2276246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-22762462008-04-09 Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis Paul, Friedemann Waiczies, Sonia Wuerfel, Jens Bellmann-Strobl, Judith Dörr, Jan Waiczies, Helmar Haertle, Mareile Wernecke, Klaus D. Volk, Hans-Dieter Aktas, Orhan Zipp, Frauke PLoS One Research Article BACKGROUND: Recent data from animal models of multiple sclerosis (MS) and from a pilot study indicated a possible beneficial impact of statins on MS. METHODOLOGY/PRINCIPAL FINDINGS: Safety, tolerability and effects on disease activity of atorvastatin given alone or in combination with interferon-beta (IFN-β) were assessed in a phase II open-label baseline-to-treatment trial in relapsing-remitting MS (RRMS). Patients with at least one gadolinium-enhancing lesion (CEL) at screening by magnetic resonance imaging (MRI) were eligible for the study. After a baseline period of 3 monthly MRI scans (months −2 to 0), patients followed a 9-month treatment period on 80 mg atorvastatin daily. The number of CEL in treatment months 6 to 9 compared to baseline served as the primary endpoint. Other MRI-based parameters as well as changes in clinical scores and immune responses served as secondary endpoints. Of 80 RRMS patients screened, 41 were included, among them 16 with IFN-β comedication. The high dose of 80 mg atorvastatin was well tolerated in the majority of patients, regardless of IFN-β comedication. Atorvastatin treatment led to a substantial reduction in the number and volume of CEL in two-sided multivariate analysis (p = 0.003 and p = 0.008). A trend towards a significant decrease in number and volume of CEL was also detected in patients with IFN-β comedication (p = 0.060 and p = 0.062), in contrast to patients without IFN-β comedication (p = 0.170 and p = 0.140). Immunological investigations showed no suppression in T cell response but a significant increase in IL-10 production. CONCLUSIONS/SIGNIFICANCE: Our data suggest that high-dose atorvastatin treatment in RRMS is safe and well tolerated. Moreover, MRI analysis indicates a possible beneficial effect of atorvastatin, alone or in combination with IFN-β, on the development of new CEL. Thus, our findings provide a rationale for phase II/III trials, including combination of atorvastatin with already approved immunomodulatory therapy regimens. TRIAL REGISTRATION: ClinicalTrials.gov NCT00616187 Public Library of Science 2008-04-09 /pmc/articles/PMC2276246/ /pubmed/18398457 http://dx.doi.org/10.1371/journal.pone.0001928 Text en Paul et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Paul, Friedemann Waiczies, Sonia Wuerfel, Jens Bellmann-Strobl, Judith Dörr, Jan Waiczies, Helmar Haertle, Mareile Wernecke, Klaus D. Volk, Hans-Dieter Aktas, Orhan Zipp, Frauke Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis |
title | Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis |
title_full | Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis |
title_fullStr | Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis |
title_full_unstemmed | Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis |
title_short | Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis |
title_sort | oral high-dose atorvastatin treatment in relapsing-remitting multiple sclerosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276246/ https://www.ncbi.nlm.nih.gov/pubmed/18398457 http://dx.doi.org/10.1371/journal.pone.0001928 |
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