title: Use of natalizumab in multiple sclerosis: current perspectives.
abstract: Natalizumab is an efficacious monoclonal antibody approved for use in relapsing-remitting multiple sclerosis (RRMS). Multiple studies have demonstrated reduced relapse rate, decreased disability progression and prolonged disease-free intervals with natalizumab use. However, natalizumab is associated with an increased risk of progressive multifocal leukoencephalopathy (PML), thus restricting its widespread use with populations at high risk for developing PML. Recently, the effect of natalizumab in secondary-progressive (SPMS) population has been explored.
  
  
  
  This review highlights the pathophysiology behind disease progression in MS and summarizes various attributes of natalizumab including: its pharmacological properties and global economic impact, results of clinical efficacy studies, its role in SPMS, pregnancy and its adverse events profile including PML and discontinuation protocols.
  
  
  
  Despite an established role in reducing RRMS disease activity, natalizumab has found limited use in SPMS due to insufficient evidence of efficacy. Current disease-modifying therapies exert modest overall benefit in SPMS owing to its complex pathophysiology, higher prevalence of comorbidities and increased PML risk with age and lack of reliable outcome measures. Finding more appropriate MRI and clinical outcome measures is quintessential for designing future randomized trials and possibly exploring primary neuroprotective agents for treating SPMS.
authors.affiliation: a Buffalo Neuroimaging Analysis Center, Department of Neurology , University at Buffalo, State University of New York , Buffalo , NY , USA.
authors.forename: Sirin
authors.initials: S
authors.lastname: Gandhi
authors.affiliation: a Buffalo Neuroimaging Analysis Center, Department of Neurology , University at Buffalo, State University of New York , Buffalo , NY , USA.
authors.forename: Dejan
authors.initials: D
authors.lastname: Jakimovski
authors.affiliation: a Buffalo Neuroimaging Analysis Center, Department of Neurology , University at Buffalo, State University of New York , Buffalo , NY , USA.
authors.forename: Rahil
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: b Jacobs MS Center, Department of Neurology , University at Buffalo, State University of New York , Buffalo , NY , USA.
authors.forename: David
authors.initials: D
authors.lastname: Hojnacki
authors.affiliation: b Jacobs MS Center, Department of Neurology , University at Buffalo, State University of New York , Buffalo , NY , USA.
authors.forename: Channa
authors.initials: C
authors.lastname: Kolb
authors.affiliation: b Jacobs MS Center, Department of Neurology , University at Buffalo, State University of New York , Buffalo , NY , USA.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: a Buffalo Neuroimaging Analysis Center, Department of Neurology , University at Buffalo, State University of New York , Buffalo , NY , USA.|c MR Imaging Clinical Translational Research Center, School of Medicine and Biomedical Sciences , University at Buffalo, State University of New York , Buffalo , NY , USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D018450:Disease Progression; D006801:Humans; D007155:Immunologic Factors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D000069442:Natalizumab / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab
keywords: MRI; Multiple sclerosis; brain atrophy; disability progression; monoclonal antibodies; natalizumab; progressive multifocal leukoencephalopathy; relapse rate