Randomized controlled trial of atorvastatin in clinically isolated syndrome

The STAyCIS study

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, Peter Calabresi, A. Miller, M. Mokhtarani, D. Iklé, S. Murphy & 5 others H. Kopetskie, L. Ding, E. Rosenberg, C. Spencer, S. S. Zamvil

Research output: Contribution to journalArticle

Abstract

Objective: To test efficacy and safety of atorvastatin in subjects with clinically isolated syndrome (CIS). Methods: Subjects with CIS were enrolled in a phase II, double-blind, placebo-controlled, 14-center randomized trial testing 80mgatorvastatin on clinical and brain MRI activity. Brain MRIs were performed quarterly.Theprimary endpoint (PEP)wasdevelopmentof≥3newT2lesions, oroneclinical relapse within 12months. Subjects meeting the PEP were offered additional weekly interferonβ-1a (IFNβ-1a). Results: Due to slow recruitment, enrollment was discontinued after 81 of 152 planned subjects with CIS were randomized and initiated study drug. Median (interquartile range) numbers of T2 and gadolinium-enhancing (Gd) lesions were 15.0 (22.0) and 0.0 (0.0) at baseline. A total of 53.1% of atorvastatin recipients (n = 26/49) met PEP compared to 56.3% of placebo recipients (n = 18/32) (p = 0.82). Eleven atorvastatin subjects (22.4%) and 7 placebo subjects (21.9%) met the PEP by clinical criteria. Proportion of subjects who did not develop new T2 lesions up to month 12 or to starting IFNβ-1a was 55.3% in the atorvastatin and 27.6% in the placebo group (p = 0.03). Likelihood of remaining free of new T2 lesions was significantly greater in the atorvastatin group compared with placebo (odds ratio [OR] = 4.34, p = 0.01). Likelihood of remaining free of Gd lesions tended to be higher in the atorvastatin group (OR=2.72, p=0.11). Overall, atorvastatin was well tolerated. No clear antagonistic effect of atorvastatin plus IFNβ-1a was observed on MRI measures. Conclusion: Atorvastatin treatment significantly decreased development of new brain MRI T2 lesion activity, although it did not achieve the composite clinical and imaging PEP. Classification of Evidence: This study provided Class II evidence that atorvastatin did not reduce the proportion of patients with CIS meeting imaging and clinical criteria for starting immunomodulating therapy after 12 months, compared to placebo. In an analysis of a secondary endpoint (Class III), atorvastatin was associated with a reduced risk for developing new T2 lesions.

Original languageEnglish (US)
Pages (from-to)1171-1178
Number of pages8
JournalNeurology
Volume78
Issue number15
DOIs
StatePublished - Apr 10 2012

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Randomized Controlled Trials
Placebos
Interferons
Gadolinium
Brain
Atorvastatin Calcium
Placebo
Randomized Controlled Trial
Lesion
Syndrome
Odds Ratio
Peptamen
Safety
Recurrence
Recipient
Imaging
Proportion
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Waubant, E., Pelletier, D., Mass, M., Cohen, J. A., Kita, M., Cross, A., ... Zamvil, S. S. (2012). Randomized controlled trial of atorvastatin in clinically isolated syndrome: The STAyCIS study. Neurology, 78(15), 1171-1178. https://doi.org/10.1212/WNL.0b013e31824f7fdd

Randomized controlled trial of atorvastatin in clinically isolated syndrome : The STAyCIS study. / Waubant, E.; Pelletier, D.; Mass, M.; Cohen, J. A.; Kita, M.; Cross, A.; Bar-Or, A.; Vollmer, T.; Racke, M.; Stüve, O.; Schwid, S.; Goodman, A.; Kachuck, N.; Preiningerova, J.; Weinstock-Guttman, B.; Calabresi, Peter; Miller, A.; Mokhtarani, M.; Iklé, D.; Murphy, S.; Kopetskie, H.; Ding, L.; Rosenberg, E.; Spencer, C.; Zamvil, S. S.

In: Neurology, Vol. 78, No. 15, 10.04.2012, p. 1171-1178.

Research output: Contribution to journalArticle

Waubant, E, Pelletier, D, Mass, M, Cohen, JA, Kita, M, Cross, A, Bar-Or, A, Vollmer, T, Racke, M, Stüve, O, Schwid, S, Goodman, A, Kachuck, N, Preiningerova, J, Weinstock-Guttman, B, Calabresi, P, Miller, A, Mokhtarani, M, Iklé, D, Murphy, S, Kopetskie, H, Ding, L, Rosenberg, E, Spencer, C & Zamvil, SS 2012, 'Randomized controlled trial of atorvastatin in clinically isolated syndrome: The STAyCIS study', Neurology, vol. 78, no. 15, pp. 1171-1178. https://doi.org/10.1212/WNL.0b013e31824f7fdd
Waubant E, Pelletier D, Mass M, Cohen JA, Kita M, Cross A et al. Randomized controlled trial of atorvastatin in clinically isolated syndrome: The STAyCIS study. Neurology. 2012 Apr 10;78(15):1171-1178. https://doi.org/10.1212/WNL.0b013e31824f7fdd
Waubant, E. ; Pelletier, D. ; Mass, M. ; Cohen, J. A. ; Kita, M. ; Cross, A. ; Bar-Or, A. ; Vollmer, T. ; Racke, M. ; Stüve, O. ; Schwid, S. ; Goodman, A. ; Kachuck, N. ; Preiningerova, J. ; Weinstock-Guttman, B. ; Calabresi, Peter ; Miller, A. ; Mokhtarani, M. ; Iklé, D. ; Murphy, S. ; Kopetskie, H. ; Ding, L. ; Rosenberg, E. ; Spencer, C. ; Zamvil, S. S. / Randomized controlled trial of atorvastatin in clinically isolated syndrome : The STAyCIS study. In: Neurology. 2012 ; Vol. 78, No. 15. pp. 1171-1178.
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abstract = "Objective: To test efficacy and safety of atorvastatin in subjects with clinically isolated syndrome (CIS). Methods: Subjects with CIS were enrolled in a phase II, double-blind, placebo-controlled, 14-center randomized trial testing 80mgatorvastatin on clinical and brain MRI activity. Brain MRIs were performed quarterly.Theprimary endpoint (PEP)wasdevelopmentof≥3newT2lesions, oroneclinical relapse within 12months. Subjects meeting the PEP were offered additional weekly interferonβ-1a (IFNβ-1a). Results: Due to slow recruitment, enrollment was discontinued after 81 of 152 planned subjects with CIS were randomized and initiated study drug. Median (interquartile range) numbers of T2 and gadolinium-enhancing (Gd) lesions were 15.0 (22.0) and 0.0 (0.0) at baseline. A total of 53.1{\%} of atorvastatin recipients (n = 26/49) met PEP compared to 56.3{\%} of placebo recipients (n = 18/32) (p = 0.82). Eleven atorvastatin subjects (22.4{\%}) and 7 placebo subjects (21.9{\%}) met the PEP by clinical criteria. Proportion of subjects who did not develop new T2 lesions up to month 12 or to starting IFNβ-1a was 55.3{\%} in the atorvastatin and 27.6{\%} in the placebo group (p = 0.03). Likelihood of remaining free of new T2 lesions was significantly greater in the atorvastatin group compared with placebo (odds ratio [OR] = 4.34, p = 0.01). Likelihood of remaining free of Gd lesions tended to be higher in the atorvastatin group (OR=2.72, p=0.11). Overall, atorvastatin was well tolerated. No clear antagonistic effect of atorvastatin plus IFNβ-1a was observed on MRI measures. Conclusion: Atorvastatin treatment significantly decreased development of new brain MRI T2 lesion activity, although it did not achieve the composite clinical and imaging PEP. Classification of Evidence: This study provided Class II evidence that atorvastatin did not reduce the proportion of patients with CIS meeting imaging and clinical criteria for starting immunomodulating therapy after 12 months, compared to placebo. In an analysis of a secondary endpoint (Class III), atorvastatin was associated with a reduced risk for developing new T2 lesions.",
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T1 - Randomized controlled trial of atorvastatin in clinically isolated syndrome

T2 - The STAyCIS study

AU - Waubant, E.

AU - Pelletier, D.

AU - Mass, M.

AU - Cohen, J. A.

AU - Kita, M.

AU - Cross, A.

AU - Bar-Or, A.

AU - Vollmer, T.

AU - Racke, M.

AU - Stüve, O.

AU - Schwid, S.

AU - Goodman, A.

AU - Kachuck, N.

AU - Preiningerova, J.

AU - Weinstock-Guttman, B.

AU - Calabresi, Peter

AU - Miller, A.

AU - Mokhtarani, M.

AU - Iklé, D.

AU - Murphy, S.

AU - Kopetskie, H.

AU - Ding, L.

AU - Rosenberg, E.

AU - Spencer, C.

AU - Zamvil, S. S.

PY - 2012/4/10

Y1 - 2012/4/10

N2 - Objective: To test efficacy and safety of atorvastatin in subjects with clinically isolated syndrome (CIS). Methods: Subjects with CIS were enrolled in a phase II, double-blind, placebo-controlled, 14-center randomized trial testing 80mgatorvastatin on clinical and brain MRI activity. Brain MRIs were performed quarterly.Theprimary endpoint (PEP)wasdevelopmentof≥3newT2lesions, oroneclinical relapse within 12months. Subjects meeting the PEP were offered additional weekly interferonβ-1a (IFNβ-1a). Results: Due to slow recruitment, enrollment was discontinued after 81 of 152 planned subjects with CIS were randomized and initiated study drug. Median (interquartile range) numbers of T2 and gadolinium-enhancing (Gd) lesions were 15.0 (22.0) and 0.0 (0.0) at baseline. A total of 53.1% of atorvastatin recipients (n = 26/49) met PEP compared to 56.3% of placebo recipients (n = 18/32) (p = 0.82). Eleven atorvastatin subjects (22.4%) and 7 placebo subjects (21.9%) met the PEP by clinical criteria. Proportion of subjects who did not develop new T2 lesions up to month 12 or to starting IFNβ-1a was 55.3% in the atorvastatin and 27.6% in the placebo group (p = 0.03). Likelihood of remaining free of new T2 lesions was significantly greater in the atorvastatin group compared with placebo (odds ratio [OR] = 4.34, p = 0.01). Likelihood of remaining free of Gd lesions tended to be higher in the atorvastatin group (OR=2.72, p=0.11). Overall, atorvastatin was well tolerated. No clear antagonistic effect of atorvastatin plus IFNβ-1a was observed on MRI measures. Conclusion: Atorvastatin treatment significantly decreased development of new brain MRI T2 lesion activity, although it did not achieve the composite clinical and imaging PEP. Classification of Evidence: This study provided Class II evidence that atorvastatin did not reduce the proportion of patients with CIS meeting imaging and clinical criteria for starting immunomodulating therapy after 12 months, compared to placebo. In an analysis of a secondary endpoint (Class III), atorvastatin was associated with a reduced risk for developing new T2 lesions.

AB - Objective: To test efficacy and safety of atorvastatin in subjects with clinically isolated syndrome (CIS). Methods: Subjects with CIS were enrolled in a phase II, double-blind, placebo-controlled, 14-center randomized trial testing 80mgatorvastatin on clinical and brain MRI activity. Brain MRIs were performed quarterly.Theprimary endpoint (PEP)wasdevelopmentof≥3newT2lesions, oroneclinical relapse within 12months. Subjects meeting the PEP were offered additional weekly interferonβ-1a (IFNβ-1a). Results: Due to slow recruitment, enrollment was discontinued after 81 of 152 planned subjects with CIS were randomized and initiated study drug. Median (interquartile range) numbers of T2 and gadolinium-enhancing (Gd) lesions were 15.0 (22.0) and 0.0 (0.0) at baseline. A total of 53.1% of atorvastatin recipients (n = 26/49) met PEP compared to 56.3% of placebo recipients (n = 18/32) (p = 0.82). Eleven atorvastatin subjects (22.4%) and 7 placebo subjects (21.9%) met the PEP by clinical criteria. Proportion of subjects who did not develop new T2 lesions up to month 12 or to starting IFNβ-1a was 55.3% in the atorvastatin and 27.6% in the placebo group (p = 0.03). Likelihood of remaining free of new T2 lesions was significantly greater in the atorvastatin group compared with placebo (odds ratio [OR] = 4.34, p = 0.01). Likelihood of remaining free of Gd lesions tended to be higher in the atorvastatin group (OR=2.72, p=0.11). Overall, atorvastatin was well tolerated. No clear antagonistic effect of atorvastatin plus IFNβ-1a was observed on MRI measures. Conclusion: Atorvastatin treatment significantly decreased development of new brain MRI T2 lesion activity, although it did not achieve the composite clinical and imaging PEP. Classification of Evidence: This study provided Class II evidence that atorvastatin did not reduce the proportion of patients with CIS meeting imaging and clinical criteria for starting immunomodulating therapy after 12 months, compared to placebo. In an analysis of a secondary endpoint (Class III), atorvastatin was associated with a reduced risk for developing new T2 lesions.

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