Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy.
A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Our objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing-remitting multiple sclerosis patients, aged 18-50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 microg (three times weekly) for 12 months, were randomized to combination therapy (interferon + atorvastatin 20 mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A (n = 21) or B (n = 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline (p = 0.007) and significantly fewer relapses versus the two pre-randomization years (p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p = 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone.
Federico University, Neurological Sciences Department, Naples, Italy. robertalanzillo@libero.it
Roberta
R
Lanzillo
Giuseppe
G
Orefice
Mario
M
Quarantelli
Carlo
C
Rinaldi
Anna
A
Prinster
Gianluca
G
Ventrella
Daniele
D
Spitaleri
Giacomo
G
Lus
Giovanni
G
Vacca
Barbara
B
Carotenuto
Elena
E
Salvatore
Arturo
A
Brunetti
Gioacchino
G
Tedeschi
Vincenzo
V
Brescia Morra
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069059:Atorvastatin; D016009:Chi-Square Distribution; D003287:Contrast Media; D004185:Disability Evaluation; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy*; D011237:Predictive Value of Tests; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D003287:Contrast Media; D006538:Heptanoic Acids; D011758:Pyrroles; D016899:Interferon-beta; D000069059:Atorvastatin; D000068556:Interferon beta-1a