COMBINING BETA INTERFERON AND ATORVASTATIN MAY INCREASE DISEASE ACTIVITY IN MULTIPLE SCLEROSIS

We read with interest the report by Birnbaum et al.1 They report results that differ from multiple studies testing interferon beta (IFNΒ) and statin combination therapy in patients with multiple sclerosis (MS). We completed a 12-month study of 10 patients with clinically isolated syndrome (CIS) suggestive of MS in which simvastatin was added in a high dose (80 mg) to an IFNΒ-1a weekly intramuscular therapy in a placebo-controlled approach. We reported that combination therapy was safe and well tolerated in this pilot study. All patients remained clinically stable.2 Our second ongoing placebo-controlled clinical trial in patients with CIS testing high-dose IFNΒ-1a and high-dose atorvastatin (80 mg) combination therapy has enrolled 30 patients, 14 of whom completed a 12-month treatment. The treatment was well tolerated, and only three patients whose assignment is still blinded had clinical relapse.3 Our in vitro Affymetrix gene expression study on peripheral blood mononuclear cells derived from 15 patients with CIS before treatment onset and 7 matched healthy controls did not show inhibition of IFNΒ-induced genes in cultures co-treated with simvastatin.2 Similarly, interim analysis of a SIMCOMBIN study that has reported data on 47 patients randomized to IFNΒ-1a alone or to a combination of IFNΒ-1a with simvastatin (80 mg daily) reported a comparable annualized relapse rate and the expression of IFNΒ biomarkers in both treatment groups.4 A gene expression study by Rudick et al.5 in 40 patients treated with both IFNΒ-1a and 20 mg of simvastatin found no evidence that statins antagonize the IFNΒ effects. All the above-mentioned studies have used high-dose statins in combination with IFNΒ. The above results are consistent with the open-label baseline-to-treatment study by Friedmann et al.,6 who reported a significant decrease in the number and volume of Gd-enhancing …