Literature DB >> 19506220

Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.

R A Rudick1, A Pace, M R S Rani, R Hyde, M Panzara, S Appachi, J Shrock, S L Maurer, P A Calabresi, C Confavreux, S L Galetta, F D Lublin, E-W Radue, R M Ransohoff.   

Abstract

BACKGROUND: Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS).
METHODS: We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40).
RESULTS: No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes.
CONCLUSIONS: Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.

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Year:  2009        PMID: 19506220      PMCID: PMC2837592          DOI: 10.1212/WNL.0b013e3181a92b96

Source DB:  PubMed          Journal:  Neurology        ISSN: 0028-3878            Impact factor:   9.910


  10 in total

1.  Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK.

Authors:  M A del Pozo; L S Price; N B Alderson; X D Ren; M A Schwartz
Journal:  EMBO J       Date:  2000-05-02       Impact factor: 11.598

2.  Tackling multiple sclerosis.

Authors:  Hartmut Wekerle
Journal:  Nature       Date:  2002-11-07       Impact factor: 49.962

3.  Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis.

Authors:  Jennifer G Robinson; Brian Smith; Nidhi Maheshwari; Helmut Schrott
Journal:  J Am Coll Cardiol       Date:  2005-10-24       Impact factor: 24.094

4.  Cell-type and donor-specific transcriptional responses to interferon-alpha. Use of customized gene arrays.

Authors:  Joerg F Schlaak; Catharien M U Hilkens; Ana P Costa-Pereira; Birgit Strobl; Fritz Aberger; Anna-Maria Frischauf; Ian M Kerr
Journal:  J Biol Chem       Date:  2002-10-16       Impact factor: 5.157

5.  The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease.

Authors:  Sawsan Youssef; Olaf Stüve; Juan C Patarroyo; Pedro J Ruiz; Jennifer L Radosevich; Eun Mi Hur; Manuel Bravo; Dennis J Mitchell; Raymond A Sobel; Lawrence Steinman; Scott S Zamvil
Journal:  Nature       Date:  2002-11-07       Impact factor: 49.962

6.  Requirement of catalytically active Tyk2 and accessory signals for the induction of TRAIL mRNA by IFN-beta.

Authors:  M R Sandhya Rani; Sudha Pandalai; Jennifer Shrock; Alex Almasan; Richard M Ransohoff
Journal:  J Interferon Cytokine Res       Date:  2007-09       Impact factor: 2.607

7.  Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis.

Authors:  G Birnbaum; B Cree; I Altafullah; M Zinser; A T Reder
Journal:  Neurology       Date:  2008-06-04       Impact factor: 9.910

8.  Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Authors:  Richard A Rudick; William H Stuart; Peter A Calabresi; Christian Confavreux; Steven L Galetta; Ernst-Wilhelm Radue; Fred D Lublin; Bianca Weinstock-Guttman; Daniel R Wynn; Frances Lynn; Michael A Panzara; Alfred W Sandrock
Journal:  N Engl J Med       Date:  2006-03-02       Impact factor: 91.245

9.  Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha.

Authors:  M R Rani; G R Foster; S Leung; D Leaman; G R Stark; R M Ransohoff
Journal:  J Biol Chem       Date:  1996-09-13       Impact factor: 5.157

10.  Increased gene expression of novel cytosolic and secretory phospholipase A(2) types in human airway epithelial cells induced by tumor necrosis factor-alpha and IFN-gamma.

Authors:  John Lindbom; Anders G Ljungman; Mats Lindahl; Christer Tagesson
Journal:  J Interferon Cytokine Res       Date:  2002-09       Impact factor: 2.607

  10 in total
  19 in total

Review 1.  Statins for multiple sclerosis.

Authors:  Jin Wang; Yousheng Xiao; Man Luo; Hongye Luo
Journal:  Cochrane Database Syst Rev       Date:  2011-12-07

2.  Multiple sclerosis: combination therapy in MS--still a valid strategy.

Authors:  Bernd C Kieseier; Olaf Stüve
Journal:  Nat Rev Neurol       Date:  2011-10-18       Impact factor: 42.937

3.  Chronic mild stress eliminates the neuroprotective effect of Copaxone after CNS injury.

Authors:  Igor Smirnov; James T Walsh; Jonathan Kipnis
Journal:  Brain Behav Immun       Date:  2013-01-04       Impact factor: 7.217

4.  Inhibition of interferon-beta responses in multiple sclerosis immune cells associated with high-dose statins.

Authors:  Xuan Feng; Diana Han; Bharat K Kilaru; Beverly S Franek; Timothy B Niewold; Anthony T Reder
Journal:  Arch Neurol       Date:  2012-10

Review 5.  3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in the treatment of central nervous system diseases.

Authors:  Joshua Z Willey; Mitchell S V Elkind
Journal:  Arch Neurol       Date:  2010-09

6.  Randomized controlled trial of atorvastatin in clinically isolated syndrome: the STAyCIS study.

Authors:  E Waubant; D Pelletier; M Mass; J A Cohen; M Kita; A Cross; A Bar-Or; T Vollmer; M Racke; O Stüve; S Schwid; A Goodman; N Kachuck; J Preiningerova; B Weinstock-Guttman; P A Calabresi; A Miller; M Mokhtarani; D Iklé; S Murphy; H Kopetskie; L Ding; E Rosenberg; C Spencer; S S Zamvil
Journal:  Neurology       Date:  2012-03-28       Impact factor: 9.910

Review 7.  Statin treatment in multiple sclerosis: a systematic review and meta-analysis.

Authors:  Gorm Pihl-Jensen; Anna Tsakiri; Jette Lautrup Frederiksen
Journal:  CNS Drugs       Date:  2015-04       Impact factor: 5.749

8.  Combinatorial Effect of Metformin and Lovastatin Impedes T-cell Autoimmunity and Neurodegeneration in Experimental Autoimmune Encephalomyelitis.

Authors:  Ajaib S Paintlia; Sarumathi Mohan; Inderjit Singh
Journal:  J Clin Cell Immunol       Date:  2013-06-30

9.  Interference with RhoA-ROCK signaling mechanism in autoreactive CD4+ T cells enhances the bioavailability of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis.

Authors:  Ajaib S Paintlia; Manjeet K Paintlia; Bruce W Hollis; Avtar K Singh; Inderjit Singh
Journal:  Am J Pathol       Date:  2012-07-13       Impact factor: 4.307

Review 10.  Failed, Interrupted, or Inconclusive Trials on Neuroprotective and Neuroregenerative Treatment Strategies in Multiple Sclerosis: Update 2015-2020.

Authors:  Niklas Huntemann; Leoni Rolfes; Marc Pawlitzki; Tobias Ruck; Steffen Pfeuffer; Heinz Wiendl; Sven G Meuth
Journal:  Drugs       Date:  2021-06-04       Impact factor: 9.546

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