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.


RESULTS
Safety, tolerability and effects on disease activity of atorvastatin given alone or in combination with interferon-beta (IFN-beta) 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-beta comedication. The high dose of 80 mg atorvastatin was well tolerated in the majority of patients, regardless of IFN-beta 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-beta comedication (p = 0.060 and p = 0.062), in contrast to patients without IFN-beta 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
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-beta, 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.


BACKGROUND
ClinicalTrials.gov NCT00616187.
Paul
Friedemann
F
Cecilie Vogt Clinic for Neurology in the HELIOS Clinic Berlin-Buch, Charité-University Medicine Berlin and Max-Delbrueck Center for Molecular Medicine, Berlin, Germany.
Waiczies
Sonia
S
Wuerfel
Jens
J
Bellmann-Strobl
Judith
J
Dörr
Jan
J
Waiczies
Helmar
H
Haertle
Mareile
M
Wernecke
Klaus D
KD
Volk
Hans-Dieter
HD
Aktas
Orhan
O
Zipp
Frauke
F
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000284:Administration, Oral; D000069059:Atorvastatin; D005682:Gadolinium / Q000494:pharmacology; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D016899:Interferon-beta / Q000627:therapeutic use; D007378:Interleukins / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008954:Models, Biological; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D015999:Multivariate Analysis; D011758:Pyrroles / Q000008:administration & dosage* / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007378:Interleukins; D011758:Pyrroles; D016899:Interferon-beta; D000069059:Atorvastatin; D005682:Gadolinium; C422042:interleukin 20