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Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial.
Lancet Neurol 2011; 10(8):691-701LN

Abstract

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.

Authors+Show Affiliations

Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. pss@rh.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase IV
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21742556

Citation

Sorensen, Per Soelberg, et al. "Simvastatin as Add-on Therapy to Interferon Β-1a for Relapsing-remitting Multiple Sclerosis (SIMCOMBIN Study): a Placebo-controlled Randomised Phase 4 Trial." The Lancet. Neurology, vol. 10, no. 8, 2011, pp. 691-701.
Sorensen PS, Lycke J, Erälinna JP, et al. Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol. 2011;10(8):691-701.
Sorensen, P. S., Lycke, J., Erälinna, J. P., Edland, A., Wu, X., Frederiksen, J. L., ... Sondergaard, H. B. (2011). Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. The Lancet. Neurology, 10(8), pp. 691-701. doi:10.1016/S1474-4422(11)70144-2.
Sorensen PS, et al. Simvastatin as Add-on Therapy to Interferon Β-1a for Relapsing-remitting Multiple Sclerosis (SIMCOMBIN Study): a Placebo-controlled Randomised Phase 4 Trial. Lancet Neurol. 2011;10(8):691-701. PubMed PMID: 21742556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. AU - Sorensen,Per Soelberg, AU - Lycke,Jan, AU - Erälinna,Juha-Pekka, AU - Edland,Astrid, AU - Wu,Xingchen, AU - Frederiksen,Jette Lautrup, AU - Oturai,Annette, AU - Malmeström,Clas, AU - Stenager,Egon, AU - Sellebjerg,Finn, AU - Sondergaard,Helle Bach, AU - ,, PY - 2011/7/12/entrez PY - 2011/7/12/pubmed PY - 2011/9/23/medline SP - 691 EP - 701 JF - The Lancet. Neurology JO - Lancet Neurol VL - 10 IS - 8 N2 - 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. SN - 1474-4465 UR - https://www.unboundmedicine.com/medline/citation/21742556/Simvastatin_as_add_on_therapy_to_interferon_β_1a_for_relapsing_remitting_multiple_sclerosis__SIMCOMBIN_study_:_a_placebo_controlled_randomised_phase_4_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1474-4422(11)70144-2 DB - PRIME DP - Unbound Medicine ER -