Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

Mult Scler. 2016 Jun;22(7):926-34. doi: 10.1177/1352458515605908. Epub 2015 Oct 2.


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.

Keywords: Progressive multiple sclerosis; cerebrospinal fluid; clinical trial; magnetization transfer ratio; methylprednisolone; osteopontin.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Biomarkers / cerebrospinal fluid
  • Bone Density
  • Denmark
  • Diffusion Tensor Imaging
  • Disease Progression
  • Evoked Potentials, Motor
  • Female
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / adverse effects
  • Humans
  • Inflammation Mediators / cerebrospinal fluid
  • Magnetic Resonance Imaging
  • Male
  • Methylprednisolone / administration & dosage*
  • Methylprednisolone / adverse effects
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid
  • Multiple Sclerosis, Chronic Progressive / diagnostic imaging
  • Multiple Sclerosis, Chronic Progressive / drug therapy
  • Multiple Sclerosis, Chronic Progressive / physiopathology
  • Neurologic Examination
  • Osteopontin / cerebrospinal fluid
  • Predictive Value of Tests
  • Pulse Therapy, Drug
  • Recovery of Function
  • Recurrence
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Biomarkers
  • Glucocorticoids
  • Inflammation Mediators
  • SPP1 protein, human
  • Osteopontin
  • Methylprednisolone