title: Extended interval dosing of natalizumab in multiple sclerosis.
abstract: BACKGROUND
  Natalizumab (NTZ), a monoclonal antibody to human α4β1/β7 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8 weeks 5 days.
  
  
  METHODS
  A retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4 weeks 3 days to 6 weeks 6 days; late extended dosing (LED; n=274) every 7 weeks to 8 weeks 5 days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4 weeks.
  
  
  RESULTS
  17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort.
  
  
  CONCLUSIONS
  Dosing intervals up to 8 weeks 5 days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID.
authors.affiliation: Department of Neurology, Langone Medical Center, New York University, New York, New York, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhovtis Ryerson
authors.affiliation: Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Frohman
authors.affiliation: Rocky Mountain MS Clinic, Salt Lake City, Utah, USA.
authors.forename: J
authors.initials: J
authors.lastname: Foley
authors.affiliation: Department of Neurology, Langone Medical Center, New York University, New York, New York, USA.
authors.forename: I
authors.initials: I
authors.lastname: Kister
authors.affiliation: University of Buffalo, Buffalo, New York, USA.
authors.forename: B
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: Georgetown University, Washington DC, USA.
authors.forename: C
authors.initials: C
authors.lastname: Tornatore
authors.affiliation: Barnabas Health MS Center, Livingston, New Jersey, USA.
authors.forename: K
authors.initials: K
authors.lastname: Pandey
authors.affiliation: CUNY Graduate Center, New York, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Donnelly
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: S
authors.initials: S
authors.lastname: Pawate
authors.affiliation: University of Massachusetts School of Medicine, Worcester, Massachusetts, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bomprezzi
authors.affiliation: Multiple Sclerosis Center of Connecticut, Norwich, Connecticut, USA.
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.affiliation: University of Buffalo, Buffalo, New York, USA.
authors.forename: C
authors.initials: C
authors.lastname: Kolb
authors.affiliation: Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: S
authors.initials: S
authors.lastname: Qureshi
authors.affiliation: Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: D
authors.initials: D
authors.lastname: Okuda
authors.affiliation: Department of Neurology, Langone Medical Center, New York University, New York, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kalina
authors.affiliation: Department of Neurology, Langone Medical Center, New York University, New York, New York, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Rimler
authors.affiliation: Barnabas Health MS Center, Livingston, New Jersey, USA.
authors.forename: R
authors.initials: R
authors.lastname: Green
authors.affiliation: Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: N
authors.initials: N
authors.lastname: Monson
authors.affiliation: Rocky Mountain MS Clinic, Salt Lake City, Utah, USA.
authors.forename: T
authors.initials: T
authors.lastname: Hoyt
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bradshaw
authors.affiliation: Department of Neurology, Langone Medical Center, New York University, New York, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Fallon
authors.affiliation: University of Alabama School of Public Health, Birmingham, Alabama, USA.
authors.forename: E
authors.initials: E
authors.lastname: Chamot
authors.affiliation: University of Buffalo, Buffalo, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bucello
authors.affiliation: Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: S
authors.initials: S
authors.lastname: Beh
authors.affiliation: University of Alabama School of Public Health, Birmingham, Alabama, USA.
authors.forename: G
authors.initials: G
authors.lastname: Cutter
authors.affiliation: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: E
authors.initials: E
authors.lastname: Major
authors.affiliation: Department of Neurology, Langone Medical Center, New York University, New York, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Herbert
authors.affiliation: Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, USA Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA Department of Bioengineering, University of Texas at Dallas, Dallas, Texas, USA Department of Behavioural and Brain Sciences, University of Texas at Dallas, Dallas, Texas, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Frohman
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D000069442:Natalizumab / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D059906:Neuroimaging; D012008:Recurrence; D012189:Retrospective Studies
chemical_list: D000069442:Natalizumab