Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.
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.
Rudick
R A
RA
Mellen Center for Treatment and Research in Multiple Sclerosis, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. rudickr@ccf.org
Pace
A
A
Rani
M R S
MR
Hyde
R
R
Panzara
M
M
Appachi
S
S
Shrock
J
J
Maurer
S L
SL
Calabresi
P A
PA
Confavreux
C
C
Galetta
S L
SL
Lublin
F D
FD
Radue
E-W
EW
Ransohoff
R M
RM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D000328:Adult; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D004347:Drug Interactions / Q000502:physiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000503:physiopathology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D006949:Hyperlipidemias / Q000188:drug therapy*; D007273:Injections, Intramuscular / Q000009:adverse effects / Q000706:statistics & numerical data; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D019169:Jurkat Cells; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D011446:Prospective Studies; D055502:Secondary Prevention; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016899:Interferon-beta; D000068556:Interferon beta-1a