@article{10.1371/journal.pone.0001928, doi = {10.1371/journal.pone.0001928}, author = {Paul, Friedemann AND Waiczies, Sonia AND Wuerfel, Jens AND Bellmann-Strobl, Judith AND Dörr, Jan AND Waiczies, Helmar AND Haertle, Mareile AND Wernecke, Klaus D. AND Volk, Hans-Dieter AND Aktas, Orhan AND Zipp, Frauke}, journal = {PLOS ONE}, publisher = {Public Library of Science}, title = {Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis}, year = {2008}, month = {04}, volume = {3}, url = {https://doi.org/10.1371/journal.pone.0001928}, pages = {1-9}, 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 NCT00616187}, number = {4}, }