title: Voxel-wise magnetization transfer imaging study of effects of natalizumab and IFNβ-1a in multiple sclerosis.
abstract: OBJECTIVE
  To determine the effects of intravenous natalizumab and intramuscular interferon beta-1a (IFNβ-1a) on the volume of white-matter (WM) lesions and normal appearing brain tissue (NABT) undergoing voxel-wise (VW) increases in magnetization transfer ratio (MTR) suggestive of remyelination in patients with relapsing multiple sclerosis.
  
  
  METHODS
  This prospective, open-label, single-blinded study enrolled patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing secondary progressive multiple sclerosis (RSPMS) as well as a group of age/sex-matched healthy controls (n=22). Patients with multiple sclerosis were assigned to receive natalizumab monotherapy (n=77; RRMS/RSPMS) or intramuscular IFNβ-1a (n=26) as either monotherapy (RRMS) or combined with pulsed i.v. methylprednisolone, as needed (RSPMS). The primary endpoint was the two-year change in volume of NABT VWMTR, by quantifying the number of voxels that increased (suggesting remyelination) or decreased (suggesting demyelination) in their MTR value.
  
  
  RESULTS
  The volume of tissue undergoing increases in VWMTR was significantly larger in natalizumab compared with IFNβ-1a-treated patients (year 1: p=0.001 in NABT and p<0.006 in WM lesions; year 2: p=0.008 in NABT) and compared with healthy control subjects (year 1: p=0.05 and year 2: p=0.007 in NABT). The larger volume within NABT undergoing decreases in VWMTR was detected in multiple sclerosis patients compared with healthy controls (p<0.001), and in the IFNβ-1a group compared with the natalizumab group (year 1: p=0.05; year 2: p=0.002). One patient on natalizumab died from progressive multifocal leukoencephalopathy eight months after completing the study.
  
  
  CONCLUSIONS
  Natalizumab may promote remyelination and stabilize demyelination in lesions and NABT in relapsing multiple sclerosis, compared with intramuscular IFNβ-1a.
authors.affiliation: Buffalo Neuroimaging Analysis Center, State University of New York, Buffalo, NY 14203, USA. rzivadinov@bnac.net
authors.forename: R
authors.initials: R
authors.lastname: Zivadinov
authors.forename: M G
authors.initials: MG
authors.lastname: Dwyer
authors.forename: S
authors.initials: S
authors.lastname: Hussein
authors.forename: E
authors.initials: E
authors.lastname: Carl
authors.forename: C
authors.initials: C
authors.lastname: Kennedy
authors.forename: M
authors.initials: M
authors.lastname: Andrews
authors.forename: D
authors.initials: D
authors.lastname: Hojnacki
authors.forename: M
authors.initials: M
authors.lastname: Heininen-Brown
authors.forename: L
authors.initials: L
authors.lastname: Willis
authors.forename: M
authors.initials: M
authors.lastname: Cherneva
authors.forename: N
authors.initials: N
authors.lastname: Bergsland
authors.forename: B
authors.initials: B
authors.lastname: Weinstock-Guttman
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D000069442:Natalizumab; D009518:New York; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020551:Pulse Therapy, Drug; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D007155:Immunologic Factors; D000069442:Natalizumab; D016899:Interferon-beta; D008775:Methylprednisolone; D000068556:Interferon beta-1a