Statins for multiple sclerosis
- PMID: 22161428
- PMCID: PMC7175839
- DOI: 10.1002/14651858.CD008386.pub3
Statins for multiple sclerosis
Abstract
Background: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. Statins, prescribed as cholesterol lowering agents, have shown possible effects for treating MS in experimental and preliminary clinical studies.
Objectives: To evaluate the efficacy and safety of statins administered alone or as add-on to approved treatments for MS.
Search methods: The Trials Search Coordinator searched the Cochrane MS Group Trials Register (1 August 2011). We searched the Chinese National Knowledge Infrastructure (CNKI) (1979 to 1 August 2011), trials registers and conference proceedings. Pharmaceutical companies and authors of included studies were contacted for additional information.There were no language restrictions.
Selection criteria: Randomised controlled trials comparing statins with placebo, or comparing statins in combination with approved treatments alone for patients with MS.
Data collection and analysis: Three review authors independently assessed trial quality and extracted data.
Main results: Four trials involving 458 participants were included. All trials compared statins (two evaluating atorvastatin and two simvastatin) plus interferon beta-1a with interferon beta-1a alone for treating MS. The methodological quality was good for three studies and poor for remaining one. None of them showed statistically significant difference between both treatment groups in reducing relapses, preventing disease progression or developing new T2 or gadolinium-enhanced lesions on MRI after 9, 12, 24 months follow up period. Statins resulted to be safe and well tolerated, no serious adverse effects were reported. Changes on quality of life after receiving statins were not reported in the trials.
Authors' conclusions: There is no convincing evidence to support the use of either atorvastatin or simvastatin as an adjunctive therapy in MS.
Conflict of interest statement
None known
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Update of
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Statins for multiple sclerosis.Cochrane Database Syst Rev. 2010 Dec 8;(12):CD008386. doi: 10.1002/14651858.CD008386.pub2. Cochrane Database Syst Rev. 2010. Update in: Cochrane Database Syst Rev. 2011 Dec 07;(12):CD008386. doi: 10.1002/14651858.CD008386.pub3. PMID: 21154395 Updated.
References
References to studies included in this review
Birnbaum 2008 {published data only}
-
- Birnbaum G, Cree B, Altafullah I, Zinser M, Reder AT. Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis. Neurology 2008;71(18):1390‐5. - PubMed
Lanzillo 2010 {published data only}
-
- Lanzillo R, Orefice G, Quarantelli M, Rinaldi C, Prinster A, Ventrella G, et al. Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing‐remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy. Multiple Sclerosis 2010;16(4):450‐4. - PubMed
-
- Orefice G, Quarantelli M, Salvatore P, Brunetti A, Lanzillo R, Prinster A, et al. An open label randomised clinical trial of atorvastatin in combination with IFN beta‐1a in active MS patients: 12 months results. Multiple Sclerosis 2007;13:S56‐7.
Sorensen 2011 {published data only}
-
- Sorensen PS, Lycke J, Eralinna JP, Edland A, Wu X, Frederiksen JL, et al. Simvastatin as add‐on therapy to interferon beta‐1a for relapsing‐remitting multiple sclerosis (SIMCOMBIN study): a placebo‐controlled randomised phase 4 trial. Lancet neurology 2011;10(8):691‐701. - PubMed
Togha 2010 {published data only}
-
- Togha M, Ahmadi Karvigh S, Nabavi M, Beladi Moghadam N, Harirchian MH, Sahraian MA, et al. Simvastatin treatment in patients with relapsing‐remitting multiple sclerosis receiving interferon beta 1a: a double blind randomized controlled trial. Multiple Sclerosis 2010;16(7):848‐854. - PubMed
References to studies excluded from this review
Bar‐Or 2007 {published data only}
-
- Bar‐Or A, Vollmer T, Antel J, Arnold DL, Bodner CA, Campagnolo D, et al. Induction of antigen‐specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo‐controlled phase 1/2 trial. Archives of Neurology 2007;64(10):1407‐15. - PubMed
Laplaud 2008 {published data only}
-
- Laplaud DA, Lefrere F, Auffray‐Calvier E, Nguyen J, Edan G, Page EL, et al. Safety, tolerance and efficacy of Pravastatin in MS‐STEP in multiple sclerosis: a randomized double‐blind placebo controlled pilot study. ECTRIMS, 24th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis; 2008 Sept 17‐20; Montreal, Canada. 2008.
Paul 2008 {published data only}
Rudick 2009 {published data only}
-
- Rudick R, Pace A, Panzara M, Rani S, Schrock J, Calabresi P, et al. Effects of statins on intramuscular interferon beta‐1afor relapsing‐remitting multiple sclerosis. Multiple Sclerosis 2007;13:S57.
Sena 2003 {published data only}
-
- Sena A, Pedrosa R, Morais MG. Therapeutic potential of lovastatin in multiple sclerosis. Journal of Neurology 2003;250(6):754‐5. - PubMed
Vollmer 2004 {published data only}
-
- Vollmer T, Key L, Durkalski V, Tyor W, Corboy J, Markovic‐Plese S, et al. Oral simvastatin treatment in relapsing‐remitting multiple sclerosis. Lancet 2004;363(9421):1607‐8. - PubMed
Wang 2008 {published data only}
-
- Wang CY, Tang JG, Tan LM, Hu ZP, Zhang HN, Guo JF. The efficacy of Simvastatin and Corticosteroid Combination Therapy in Multiple Sclerosis. Journal of Chinese Physician 2008;10(5):694‐5.
References to studies awaiting assessment
NCT00942591 {published data only}
-
- NCT00942591. Atorvastatin 40 mg in Patients With Relapsing‐Remitting Multiple Sclerosis Treated With Interferon‐Beta‐1b (SWABIMS). clinicaltrials.gov/ct2/show/NCT00942591 (accessed 1 August 2011).
NCT01111656 {published data only}
-
- NCT01111656. SWABIMS Follow Up‐study. clinicaltrials.gov/ct2/show/NCT01111656 (accessed 1 August 2011).
Öztekin 2008 {published data only}
-
- Öztekin NS, Öztekin FM, Munis OB. Atorvastatin combined with interferon beta 1a in relapsing‐remitting multiple sclerosis: preliminary results of a 24 month randomized open‐label clinical trial. ECTRIMS, 24th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis. September 17‐20, 2008.
References to ongoing studies
NCT00242268 {published data only}
-
- NCT00242268. A Safety Study of Combination Treatment With Avonex and Zocor in Relapsing Remitting Multiple Sclerosis. clinicaltrials.gov/ct2/show/NCT00242268 (accessed 1 August 2011).
NCT00429442 {published data only}
-
- NCT00429442. Simvastatin as an Add‐on Treatment to Copaxone for the Treatment of Relapsing Multiple Sclerosis. clinicaltrials.gov/ct2/show/NCT00429442 (accessed 1 August 2011).
NCT00647348 {published data only}
-
- NCT00647348. Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis (MS‐STAT). http://clinicaltrials.gov/ct2/show/NCT00647348 (accessed 1 August 2011).
Additional references
Aktas 2003
Baker 2003
-
- Baker D, Adamson P, Greenwood J. Potential of statins for the treatment of multiple sclerosis. Lancet Neurology 2003;2(1):9‐10. - PubMed
Boutron 2004
-
- Boutron I, Tubach F, Giraudeau B, Ravaud P. Blinding was judged more difficult to achieve and maintain in nonpharmacologic than pharmacologic trials. Epidemiology 2004;57(6):543‐50. - PubMed
Compston 2002
-
- Compston A, Coles A. Multiple sclerosis. Lancet 2002;359(9313):1221‐31. - PubMed
D'Amico 2010
-
- D'Amico R, Ebers G, Filippini G, Fredrikson S, Pietrantonj C, Khan F, et al. Cochrane Multiple Sclerosis Group. About The Cochrane Collaboration 2009, issue 3.
Dwan 2008
Hartung 2009
-
- Hartung HP. High‐dose, high‐frequency recombinant interferon beta‐1ain the treatment of multiple sclerosis. Expert Opinion on Pharmacotherapy 2009;10(2):291‐309. - PubMed
Higgins 2011
-
- Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Hopewell 2009
HPS 2002
-
- Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high‐risk individuals: a randomised placebo‐controlled trial. Lancet 2002;360(9326):7‐22. - PubMed
Kurtzke 1983
-
- Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33(11):1444‐52. - PubMed
Lefebrvre 2011
-
- Lefebrvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT,Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
McDonald 2001
-
- McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Annals of Neurology 2001;50(1):121‐7. - PubMed
Nath 2004
-
- Nath N, Giri S, Prasad R, Singh AK, Singh I. Potential targets of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor for multiple sclerosis therapy. Journal of Immunology 2004;172(2):1273‐86. - PubMed
Orefice 2007
-
- Orefice G, Quarantelli M, Salvatore P, Brunetti A, Lanzillo R, Prinster A, et al. An open label randomised clinical trial of atorvastatin in combination with IFN beta‐1a in active MS patients: 12 months results. Multiple Sclerosis 2007;13(2):S56‐7.
Paintlia 2005
-
- Paintlia AS, Paintlia MK, Khan M, Vollmer T, Singh AK, Singh I. HMG‐CoA reductase inhibitor augments survival and differentiation of oligodendrocyte progenitors in animal model of multiple sclerosis. The FASEB journal 2005;19(11):1407‐21. - PubMed
Peng 2006
-
- Peng X, Jin J, Giri S, Montes M, Sujkowski D, Tang Y, et al. Immunomodulatory effects of 3‐hydroxy‐3‐methylglutaryl coenzyme‐A reductase inhibitors, potential therapy for relapsing remitting multiple sclerosis. Journal of Neuroimmunology 2006;178(1‐2):130‐9. - PubMed
Polman 2005
-
- Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic Criteria for Multiple Sclerosis: 2005 revisions to the Macdonald Criteria. Annals of Neurology 2005;58(6):840‐6. - PubMed
Polman 2011
Poser 1983
-
- Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Annals of Neurology 1983;13(3):227‐31. - PubMed
Review Manager (RevMan) 2011 [Computer program]
-
- The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
Shulz 1995
-
- Shulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408‐12. - PubMed
Smyth 2011
Stanislaus 1999
-
- Stanislaus R, Pahan K, Singh AK, Singh I. Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin. Neuroscience Letters 1999;269(2):71‐4. - PubMed
Stanislaus 2001
-
- Stanislaus R, Singh AK, Singh I. Lovastatin treatment decreases mononuclear cell infiltration into the CNS of Lewis rats with experimental allergic encephalomyelitis. Journal of Neuroscience Research 2001;66(2):155‐62. - PubMed
Stanislaus 2002
-
- Stanislaus R, Gilg AG, Singh AK, Singh I. Immunomodulation of experimental autoimmune encephalomyelitis in the Lewis rats by Lovastatin. Neuroscience Letters 2002;333(3):167‐70. - PubMed
Sørensen 2007
-
- Sørensen PS, Frederiksen JL, Lycke J, Sellebjerg F. Does simvastatin antagonise the effect of interferon beta? Interim safety analysis of the ongoing SIMCOMBIN study. Multiple Sclerosis 2007;13(2):S25.
Vickrey 1995
-
- Vickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A health‐related quality of life measure for multiple sclerosis. Quality of Life Research 1995;4(3):187‐206. - PubMed
Wang 2010
-
- Wang J, Xiao Y, Luo M, Zhang X, Luo H. Statins for multiple sclerosis. Cochrane Database Syst Rev 2010;12(1469‐493X (Electronic), 1361‐6137 (Linking)):CD008386. - PubMed
Youssef 2002
-
- Youssef S, Stüve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, et al. The HMG‐CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002;420(6911):78‐84. - PubMed
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