Efficacy, Safety and Tolerability of Atorvastatin 40 mg in Patients With Relapsing-remitting Multiple Sclerosis Treated With Interferon-beta-1b

• Proportion of patients with new lesions on T2-weighted images after 12 months of treatment [ Time Frame: Month 0 ] [ Designated as safety issue: Yes ]
  
• Proportion of patients with new lesions on T2-weighted images after 12 months of treatment [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  

• Gd-enhancing lesions on T1-weighted images after 12 months of treatment. [ Time Frame: Month 0 ] [ Designated as safety issue: Yes ]
  
• Total T2-hyperintense lesion volume (burden of disease, BOD) after 12 months of treatment. [ Time Frame: Month 0 ] [ Designated as safety issue: Yes ]
  
• Cortical atrophy (changes in brain volume, changes in grey matter and white matter) on magnetic resonance imaging (MRI) after 12 months of treatment [ Time Frame: Month 0 ] [ Designated as safety issue: No ]
  
• Clinical disease progression (Expanded Disability Status Scale [EDSS], Multiple Sclerosis Functional Composite [MSFC] ) [ Time Frame: Month 0 ] [ Designated as safety issue: Yes ]
  
• Functional systems scores (of Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC] ) [ Time Frame: Month 0 ] [ Designated as safety issue: Yes ]
  
• Number of relapse-free patients after 12 months of treatment [ Time Frame: Month 0 ] [ Designated as safety issue: Yes ]
  
• Relapse rate after 12 months of treatment [ Time Frame: Month 0 ] [ Designated as safety issue: Yes ]
  
• Time to first relapse [ Time Frame: Month 0 ] [ Designated as safety issue: Yes ]
  
• Gd-enhancing lesions on T1-weighted images after 12 months of treatment. [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  
• Total T2-hyperintense lesion volume (burden of disease, BOD) after 12 months of treatment. [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  
• Cortical atrophy (changes in brain volume, changes in grey matter and white matter) on magnetic resonance imaging (MRI)after 12 months of treatment [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  
• Clinical disease progression (Expanded Disability Status Scale [EDSS] , Multiple Sclerosis Functional Composite [MSFC] ) [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  
• Functional systems scores (of Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC] ) [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  
• Number of relapse-free patients after 12 months of treatment [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  
• Relapse rate after 12 months of treatment [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  
• Time of first relapse [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
  

Background

Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system. Statins are lipid-lowering drugs which inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA-) reductase, which is the main regulatory enzyme of cholesterol biosynthesis. In recent years many studies have demonstrated, that statins have anti-inflammatory and immunomodulatory properties in addition to their lipid-lowering effects. Therefore, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Studies in experimental allergic encephalomyelitis (EAE), the animal model for the human demyelinating disease multiple sclerosis, as well as smaller studies in patients with relapsing-remitting multiple sclerosis showed beneficial effect on the course of the disease. But there are also reports of negative impact of statins on multiple sclerosis. Therefore, bigger studies are needed to investigate the therapeutical potential of statins in multiple sclerosis.

Objective

To assess the efficacy, safety and tolerability of the combination of atorvastatin 40mg p.o. daily and interferon-beta 1b sc e.o.d compared to monotherapy with interferon-beta-1b sc e.o.d in patients with relapsing-remitting multiple sclerosis for 12 month after completing the SWABIMS study.

Methods

Multi-center, rater-blinded, parallel-group, two arm, randomized study. Patients with relapsing-remitting forms of MS, respecting all inclusion/exclusion criteria, were randomized in the SWABIMS study in two equal-size parallel arms after three months of treatment with interferon-beta 1b, receiving atorvastatin 40mg/d or not in addition to interferon-beta 1b for 12 month.

After successful completion of the study, patients were asked to participate in the "SWABIMS Follow up study" for another 12 month with ongoing medication.