Simvastatin as add-on therapy to interferon beta-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial - 28/07/11
, Jan Lycke, MD b, Juha-Pekka Erälinna, MD c, Astrid Edland, MD d, Xingchen Wu, MD e, Jette Lautrup Frederiksen, MD f, Annette Oturai, MD a, Clas Malmeström, MD b, Egon Stenager, MD g, h, i, Finn Sellebjerg, MD a, Helle Bach Sondergaard, MS afor the SIMCOMBIN study investigators
Summary |
Background |
Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy.
Methods |
We enrolled treatment-naive patients with relapsing-remitting multiple sclerosis in a multicentre, placebo-controlled, double-blind, randomised, parallel-group trial of simvastatin (80 mg daily) as add-on treatment to intramuscular interferon beta-1a (30 μg weekly). After starting treatment with interferon beta, patients were randomly assigned (in computer-generated blocks of four patients) to simvastatin 80 mg per day or placebo for 1–3 years. Patients and treating and evaluating physicians were masked to treatment allocation. The primary outcome measure was annual rate of documented relapses; analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00492765.
Findings |
We randomly assigned 307 patients to interferon beta plus simvastatin (n=151) or plus placebo (n=156). Annual rate of documented relapses was 0·19 (95% CI 0·13 to 0·28) in the simvastatin group and 0·14 (95% CI 0·09 to 0·23) in the placebo group (absolute difference 0·059, 95% CI −0·21 to 0·09; p=0·35). Time to first documented relapse (20th percentile) was 18·1 months in patients on simvastatin and 21·5 months in those on placebo (hazard ratio 1·21, 95% CI 0·74 to 1·99; p=0·51). Mean number of new or enlarging T2 lesions was 2·96 in the simvastatin group and 2·52 in the placebo group (ratio of new lesions, 1·17, 95% CI 8·89 to 1·55; p=0·25). Eight (6%) patients on simvastatin and 17 (13%) on placebo had no disease activity (odds ratio 0·42, 95% CI 0·17 to 1·00; p=0·05). No unexpected adverse events were seen. Generally, adverse events were mild and there were no group differences in infections or musculoskeletal disorders, including myalgia (five [3%] patients on simvastatin and nine [6%] on placebo). Rhabdomyolysis and myoglobinuria were not reported and there were no differences in serum creatine phosphokinase.
Interpretation |
We found no beneficial effect of simvastatin as add-on therapy to interferon beta-1a. Although unlikely, we can not exclude that combination of other statins with other disease-modifying drugs still could be beneficial.
Funding |
Biogen Idec.
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Vol 10 - N° 8
P. 691-701 - août 2011 Retour au numéro
Article précédent
- News in brief
- APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study
- Alessandro Biffi, Christopher D Anderson, Jeremiasz M Jagiella, Helena Schmidt, Brett Kissela, Björn M Hansen, Jordi Jimenez-Conde, Caroline R Pires, Alison M Ayres, Kristin Schwab, Lynelle Cortellini, Joanna Pera, Andrzej Urbanik, Javier M Romero, Natalia S Rost, Joshua N Goldstein, Anand Viswanathan, Alexander Pichler, Christian Enzinger, Raquel Rabionet, Bo Norrving, David L Tirschwell, Magdy Selim, Devin L Brown, Scott L Silliman, Bradford B Worrall, James F Meschia, Chelsea S Kidwell, Joseph P Broderick, Steven M Greenberg, Jaume Roquer, Arne Lindgren, Agnieszka Slowik, Reinhold Schmidt, Daniel Woo, Jonathan Rosand, on behalf of the International Stroke Genetics Consortium
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