title: Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis.
abstract: 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.
  
  
  
  To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark rikke.ratzer@regionh.dk.
authors.forename: Rikke
authors.initials: R
authors.lastname: Ratzer
authors.affiliation: Danish Research Center for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Iversen
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Börnsen
authors.affiliation: Danish Research Center for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: Tim B
authors.initials: TB
authors.lastname: Dyrby
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Romme Christensen
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Ammitzbøll
authors.affiliation: Danish Research Center for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: Camilla Gøbel
authors.initials: CG
authors.lastname: Madsen
authors.affiliation: Danish Research Center for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: Ellen
authors.initials: E
authors.lastname: Garde
authors.affiliation: Danish Research Center for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: Mark
authors.initials: M
authors.lastname: Lyksborg
authors.affiliation: Department of Clinical Neurophysiology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Birgit
authors.initials: B
authors.lastname: Andersen
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Hyldstrup
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sørensen
authors.affiliation: Danish Research Center for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Finn
authors.initials: F
authors.lastname: Sellebjerg
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015519:Bone Density; D003718:Denmark; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D019054:Evoked Potentials, Motor; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D018836:Inflammation Mediators / Q000134:cerebrospinal fluid; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D009460:Neurologic Examination; D053495:Osteopontin / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D020551:Pulse Therapy, Drug; D020127:Recovery of Function; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D018836:Inflammation Mediators; C506895:SPP1 protein, human; D053495:Osteopontin; D008775:Methylprednisolone
keywords: Progressive multiple sclerosis; cerebrospinal fluid; clinical trial; magnetization transfer ratio; methylprednisolone; osteopontin