Simvastatin treatment in patients with relapsing-remitting multiple sclerosis receiving interferon beta 1a: a double-blind randomized controlled trial.
OBJECTIVE
This study was conducted to evaluate the effect of simvastatin (40 mg/day) as an adjuvant therapy to interferon beta (IFNb 1a, 30 microg once weekly) in relapsing-remitting multiple sclerosis patients, compared with placebo.


METHODS
We enrolled 85 patients with relapsing-remitting multiple sclerosis (71% female) who were already receiving IFNb 1a (Avonex), with Expanded Disability Status Scale score of less than 5.0. The patients were assigned (in random and double-blinded fashion) into the two groups of simvastatin and placebo. All patients continued to receive their current IFNb treatment. The outcome measures were total relapse rate, Expanded Disability Status Scale score, and the number of gadolinium-enhanced (Gd+) and new T2 lesions in magnetic resonance imaging after a 1-year follow-up. We used Mann-Whitney and one-way multivariate analysis of variances to analyze the data.


RESULTS
Four patients in the placebo and two in the simvastatin group prematurely withdrew from the study due to experiencing two attacks. The total attack number in the simvastatin group was significantly lower than placebo group (moderate effect size r = 0.29) (p = 0.01). The final Expanded Disability Status Scale scores were lower in the simvastatin group (1.01 +/- 1.40, mean +/- SD) than in the placebo group (1.73 +/- 1.49, mean +/- SD), but this difference was not significant after controlling the baseline Expanded Disability Status Scale score (p = 0.07). In the simvastatin group, the mean +/- SD of gadolinium-enhanced and new T2 lesions were 0.66 +/- 1.18 and 3.39 +/- 3.55, respectively, (compared with 0.74 +/- 1.21 and 3.39 +/- 3.55 in the placebo group). Although there was a decreasing trend in lesions on magnetic resonance imaging, this difference was not statistically significant (p = 0.62). The combination therapy was safe and well tolerated, and no serious adverse effect was noted.


CONCLUSIONS
Our study supports the safety and efficacy of simvastatin as an add-on therapy to INFb 1a in patients with relapsing-remitting multiple sclerosis.


BACKGROUND
ClinicalTrials.gov NCT00668343. This interventional study provides Class I evidence stating that adding simvastatin 40 mg/day to IFNb 1a 30 microg a week in patients with relapsing-remitting multiple sclerosis may reduce the relapse rate (moderate effect size r = 0.29) (p = 0.01) compared with treatment with IFNb 1a alone.
Togha
Mansoureh
M
Sina Hospital, Tehran, Iran.
Karvigh
Sanaz Ahmadi
SA
Nabavi
Masoud
M
Moghadam
Nahid Beladi
NB
Harirchian
Mohammad Hossein
MH
Sahraian
Mohammad Ali
MA
Enzevaei
Anahita
A
Nourian
Alireza
A
Ghanaati
Hossein
H
Firouznia
Kavous
K
Jannati
Ali
A
Shekiba
Majid
M
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D003287:Contrast Media; D004185:Disability Evaluation; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005682:Gadolinium; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use*; D007492:Iran; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy*; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000276:Adjuvants, Immunologic; D003287:Contrast Media; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007155:Immunologic Factors; D016899:Interferon-beta; D019821:Simvastatin; D005682:Gadolinium; D000068556:Interferon beta-1a