Natalizumab in progressive MS: results of an open-label, phase 2A, proof-of-concept trial

Neurology. 2014 Apr 29;82(17):1499-507. doi: 10.1212/WNL.0000000000000361. Epub 2014 Mar 28.


Objective: Natalizumab inhibits the migration of systemic immune cells to the CNS and may be beneficial in progressive multiple sclerosis (MS). The objective of the study was to examine the effects of natalizumab in progressive MS.

Methods: In an open-label phase 2A study, 24 patients with progressive MS were included to receive natalizumab treatment for 60 weeks. Response to natalizumab was assessed in CSF and MRI studies. The primary endpoint was change in CSF osteopontin, a biomarker of intrathecal inflammation, from baseline to week 60.

Results: Seventeen patients completed the study. No new safety issues were encountered. CSF osteopontin decreased by 65 ng/mL (95% confidence interval 34-96 ng/mL; p = 0.0004) from baseline to week 60 in conjunction with decreases in other CSF biomarkers of inflammation, axonal damage, and demyelination. Magnetization transfer ratio increased in both cortical gray and normal-appearing white matter and correlated with decreases in CSF neurofilament light chain.

Conclusions: Natalizumab treatment of progressive MS reduces intrathecal inflammation and tissue damage, supporting a beneficial effect of natalizumab treatment in progressive MS and suggesting that systemic inflammation contributes to the pathogenesis. Moreover, the study establishes the feasibility of using CSF biomarkers in proof-of-concept trials, allowing a low number of participants and short study duration.

Classification of evidence: This study provides Class IV evidence that in patients with progressive MS, natalizumab reduces biomarkers of intrathecal inflammation.

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cerebral Cortex / pathology
  • Chemokine CXCL13 / cerebrospinal fluid
  • Disability Evaluation
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / therapeutic use*
  • Magnetic Resonance Imaging / methods
  • Male
  • Matrix Metalloproteinase 9 / cerebrospinal fluid
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid
  • Multiple Sclerosis, Chronic Progressive / drug therapy*
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Myelin Basic Protein / cerebrospinal fluid
  • Natalizumab
  • Neurofilament Proteins / cerebrospinal fluid
  • Osteopontin / cerebrospinal fluid
  • Secondary Prevention
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • CXCL13 protein, human
  • Chemokine CXCL13
  • Immunologic Factors
  • MBP protein, human
  • Myelin Basic Protein
  • Natalizumab
  • Neurofilament Proteins
  • neurofilament protein L
  • Osteopontin
  • Matrix Metalloproteinase 9