Randomized controlled trial of atorvastatin in clinically isolated syndrome
Waubant E et al. – 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).
- 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.