Randomized controlled trial of atorvastatin in clinically isolated syndrome

Neurology®, 04/25/2012

Atorvastatin treatment significantly decreased development of new brain MRI T2 lesion activity, although it did not achieve the composite clinical and imaging primary endpoint (PEP).

Methods

  • Subjects with CIS were enrolled in a phase II, double-blind, placebo-controlled, 14-center randomized trial testing 80 mg atorvastatin on clinical and brain MRI activity.
  • Brain MRIs were performed quarterly.
  • The primary endpoint (PEP) was development of ≥3 new T2 lesions, or one clinical relapse within 12 months.
  • Subjects meeting the PEP were offered additional weekly interferon β-1a (IFNβ-1a).

Results

  • Due to slow recruitment, enrollment was discontinued after 81 of 152 planned subjects with CIS were randomized and initiated study drug.
  • Median (interquartile range) numbers of T2 and gadolinium-enhancing (Gd) lesions were 15.0 (22.0) and 0.0 (0.0) at baseline.
  • A total of 53.1% of atorvastatin recipients (n = 26/49) met PEP compared to 56.3% of placebo recipients (n = 18/32) (p = 0.82).
  • Eleven atorvastatin subjects (22.4%) and 7 placebo subjects (21.9%) met the PEP by clinical criteria.
  • Proportion of subjects who did not develop new T2 lesions up to month 12 or to starting IFNβ-1a was 55.3% in the atorvastatin and 27.6% in the placebo group (p = 0.03).
  • Likelihood of remaining free of new T2 lesions was significantly greater in the atorvastatin group compared with placebo (odds ratio [OR] = 4.34, p = 0.01).
  • Likelihood of remaining free of Gd lesions tended to be higher in the atorvastatin group (OR = 2.72, p = 0.11).
  • Overall, atorvastatin was well tolerated.
  • No clear antagonistic effect of atorvastatin plus IFNβ-1a was observed on MRI measures.

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