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.
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.
Authors: Raju Kapoor; Kathryn E Smith; Mark Allegretta; Douglas L Arnold; William Carroll; Manuel Comabella; Roberto Furlan; Christopher Harp; Jens Kuhle; David Leppert; Tatiana Plavina; Finn Sellebjerg; Caroline Sincock; Charlotte E Teunissen; Ilir Topalli; Florian von Raison; Elizabeth Walker; Robert J Fox Journal: Neurology Date: 2020-07-16 Impact factor: 9.910
Authors: Bruno Brochet; Mathilde S A Deloire; Paul Perez; Timothé Loock; Louise Baschet; Marc Debouverie; Sophie Pittion; Jean-Christophe Ouallet; Pierre Clavelou; Jérôme de Sèze; Nicolas Collongues; Patrick Vermersch; Hélène Zéphir; Giovanni Castelnovo; Pierre Labauge; Christine Lebrun; Mikael Cohen; Aurélie Ruet Journal: PLoS One Date: 2017-01-03 Impact factor: 3.240