The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis

P. D. Molyneux, L. Kappos, C. Polman, C. Pozzilli, F. Barkhof, M. Filippi, T. Yousry, D. Hahn, K. Wagner, M. Ghazi, K. Beckmann, F. Dahlke, N. Losseff, G. J. Barker, A. J. Thompson, D. H. Miller

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Abstract

The recently completed European trial of interferon beta-1b (IFNβ-1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T1-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFNβ-1b 1.8%, P <0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNβ-1b (placebo 2.6%, IFNβ-1b 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFNβ. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNβ-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease.

Original languageEnglish
Pages (from-to)2256-2263
Number of pages8
JournalBrain
Volume123
Issue number11
Publication statusPublished - 2000

Fingerprint

Chronic Progressive Multiple Sclerosis
Atrophy
Placebos
Gadolinium
Therapeutics
Automation
Cerebrum
Interferon beta-1b
Neuroimaging
Disease Progression
Anti-Inflammatory Agents
Observation

Keywords

  • Cerebral atrophy
  • Interferon beta-1b
  • MRI
  • Multiple sclerosis
  • Secondary progressive multiple sclerosis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Molyneux, P. D., Kappos, L., Polman, C., Pozzilli, C., Barkhof, F., Filippi, M., ... Miller, D. H. (2000). The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. Brain, 123(11), 2256-2263.

The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. / Molyneux, P. D.; Kappos, L.; Polman, C.; Pozzilli, C.; Barkhof, F.; Filippi, M.; Yousry, T.; Hahn, D.; Wagner, K.; Ghazi, M.; Beckmann, K.; Dahlke, F.; Losseff, N.; Barker, G. J.; Thompson, A. J.; Miller, D. H.

In: Brain, Vol. 123, No. 11, 2000, p. 2256-2263.

Research output: Contribution to journalArticle

Molyneux, PD, Kappos, L, Polman, C, Pozzilli, C, Barkhof, F, Filippi, M, Yousry, T, Hahn, D, Wagner, K, Ghazi, M, Beckmann, K, Dahlke, F, Losseff, N, Barker, GJ, Thompson, AJ & Miller, DH 2000, 'The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis', Brain, vol. 123, no. 11, pp. 2256-2263.
Molyneux, P. D. ; Kappos, L. ; Polman, C. ; Pozzilli, C. ; Barkhof, F. ; Filippi, M. ; Yousry, T. ; Hahn, D. ; Wagner, K. ; Ghazi, M. ; Beckmann, K. ; Dahlke, F. ; Losseff, N. ; Barker, G. J. ; Thompson, A. J. ; Miller, D. H. / The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. In: Brain. 2000 ; Vol. 123, No. 11. pp. 2256-2263.
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abstract = "The recently completed European trial of interferon beta-1b (IFNβ-1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T1-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9{\%}, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1{\%}, IFNβ-1b 1.8{\%}, P <0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNβ-1b (placebo 2.6{\%}, IFNβ-1b 3.7{\%}; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFNβ. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNβ-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease.",
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AU - Pozzilli, C.

AU - Barkhof, F.

AU - Filippi, M.

AU - Yousry, T.

AU - Hahn, D.

AU - Wagner, K.

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AU - Beckmann, K.

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AU - Thompson, A. J.

AU - Miller, D. H.

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N2 - The recently completed European trial of interferon beta-1b (IFNβ-1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T1-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFNβ-1b 1.8%, P <0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNβ-1b (placebo 2.6%, IFNβ-1b 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFNβ. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNβ-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease.

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