Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

Rikke Ratzer; Pernille Iversen; Lars Börnsen; Tim B Dyrby; Jeppe Romme Christensen; Cecilie Ammitzbøll; Camilla Gøbel Madsen; Ellen Garde; Mark Lyksborg; Birgit Andersen; Lars Hyldstrup; Per Soelberg Sørensen; Hartwig R Siebner; Finn Sellebjerg

doi:10.1177/1352458515605908

Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

Rikke Ratzer, Pernille Iversen, Lars Börnsen, Tim B Dyrby, Jeppe Romme Christensen, Cecilie Ammitzbøll, Camilla Gøbel Madsen, Ellen Garde, Mark Lyksborg, Birgit Andersen, Lars Hyldstrup, Per Soelberg Sørensen, Hartwig R Siebner, Finn Sellebjerg

Department of Clinical Medicine

20 Citations (Scopus)

Abstract

BACKGROUND: There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments.

OBJECTIVE: To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS.

METHODS: In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans.

RESULTS: We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone.

CONCLUSION: Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS.

Original language	English
Journal	Multiple Sclerosis Journal
Volume	22
Issue number	7
Pages (from-to)	926–934
Number of pages	9
ISSN	1352-4585
DOIs	https://doi.org/10.1177/1352458515605908
Publication status	Published - 1 Jun 2016

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Ratzer, R., Iversen, P., Börnsen, L., Dyrby, T. B., Christensen, J. R., Ammitzbøll, C., Madsen, C. G., Garde, E., Lyksborg, M., Andersen, B., Hyldstrup, L., Sørensen, P. S., Siebner, H. R., & Sellebjerg, F. (2016). Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis. Multiple Sclerosis Journal, 22(7), 926–934. https://doi.org/10.1177/1352458515605908

Ratzer, R, Iversen, P, Börnsen, L, Dyrby, TB, Christensen, JR, Ammitzbøll, C, Madsen, CG, Garde, E, Lyksborg, M, Andersen, B, Hyldstrup, L, Sørensen, PS , Siebner, HR & Sellebjerg, F 2016, 'Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis', Multiple Sclerosis Journal, vol. 22, no. 7, pp. 926–934. https://doi.org/10.1177/1352458515605908

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title = "Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis",

abstract = "BACKGROUND: There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments.OBJECTIVE: To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS.METHODS: In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans.RESULTS: We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone.CONCLUSION: Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS.",

author = "Rikke Ratzer and Pernille Iversen and Lars B{\"o}rnsen and Dyrby, {Tim B} and Christensen, {Jeppe Romme} and Cecilie Ammitzb{\o}ll and Madsen, {Camilla G{\o}bel} and Ellen Garde and Mark Lyksborg and Birgit Andersen and Lars Hyldstrup and S{\o}rensen, {Per Soelberg} and Siebner, {Hartwig R} and Finn Sellebjerg",

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AU - Ratzer, Rikke

AU - Iversen, Pernille

AU - Börnsen, Lars

AU - Dyrby, Tim B

AU - Christensen, Jeppe Romme

AU - Ammitzbøll, Cecilie

AU - Madsen, Camilla Gøbel

AU - Garde, Ellen

AU - Lyksborg, Mark

AU - Andersen, Birgit

AU - Hyldstrup, Lars

AU - Sørensen, Per Soelberg

AU - Siebner, Hartwig R

AU - Sellebjerg, Finn

PY - 2016/6/1

Y1 - 2016/6/1

N2 - BACKGROUND: There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments.OBJECTIVE: To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS.METHODS: In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans.RESULTS: We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone.CONCLUSION: Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS.

AB - BACKGROUND: There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments.OBJECTIVE: To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS.METHODS: In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans.RESULTS: We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone.CONCLUSION: Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS.

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DO - 10.1177/1352458515605908

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VL - 22

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JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

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Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

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