Oral high-dose atorvastatin treatment in relapsing-remitting multiple sclerosis |
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Authors: | 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 |
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Affiliation: | Cecilie Vogt Clinic for Neurology in the HELIOS Clinic Berlin-Buch, Charité-University Medicine Berlin and Max-Delbrueck Center for Molecular Medicine, Berlin, Germany. |
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Abstract: | BackgroundRecent data from animal models of multiple sclerosis (MS) and from a pilot study indicated a possible beneficial impact of statins on MS.Methodology/Principal FindingsSafety, 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/SignificanceOur 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 RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00616187","term_id":"NCT00616187"}}NCT00616187 |
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