title: Monitoring CD49d Receptor Occupancy: A Method to Optimize and Personalize Natalizumab Therapy in Multiple Sclerosis Patients.
abstract: In natalizumab-treated relapsing-remitting MS (RRMS) patients, various extended interval dosing strategies are under evaluation to minimize severe treatment-associated side effects, mainly progressive multifocal leukoencephalopathy development. Up to now, it has not been presented any approach, even in form of assay design, to determine the optimal percentage of CD49d receptor occupancy (RO) associated with a favorable clinical, radiological, and immunological response.
  
  
  
  A multiparametric quantitative flow cytometry method was settled to measure CD49d RO on peripheral blood lymphocytes. The analytical protocol was tested in a 6-month follow-up from 19 RRMS patients treated with the natalizumab standard dosing of every 4 weeks or an extended-interval dosing of every 6 weeks.
  
  
  
  Extended natalizumab dose schedule promoted an increase of CD49d molecules per cell surface and a reduction of CD49d RO levels. The reduction observed on CD49d RO was not only depending on dose schedule but also on individual parameters such as body mass. Interestingly, individual clinical outcome was apparently the same between the different dose schedules or even better with the extended interval dosing.
  
  
  
  Following up CD49d RO levels with a well-regulated monitoring work scheme is crucial to further identify over-/under-treated patients and to define a safe, personalized natalizumab regimen. © 2017 International Clinical Cytometry Society.
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain.|Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Puñet-Ortiz
authors.affiliation: Department of Neuroscience, Multiple Sclerosis Unit, University Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: José Vicente
authors.initials: JV
authors.lastname: Hervás-García
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain.|Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Spain.
authors.forename: Aina
authors.initials: A
authors.lastname: Teniente-Serra
authors.affiliation: Neurology Service, Consorci Sanitari del Maresme, Mataró, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cano-Orgaz
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain.|Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Mansilla
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain.|Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Spain.
authors.forename: Bibiana
authors.initials: B
authors.lastname: Quirant-Sánchez
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain.|Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Navarro-Barriuso
authors.affiliation: Flow Cytometry Facility, Germans Trias i Pujol Research Institute, Campus Can Ruti, Badalona, Spain.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Fernández-Sanmartín
authors.affiliation: Department of Neuroscience, Multiple Sclerosis Unit, University Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Presas-Rodríguez
authors.affiliation: Department of Neuroscience, Multiple Sclerosis Unit, University Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ramo-Tello
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain.|Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Spain.
authors.forename: Eva María
authors.initials: EM
authors.lastname: Martínez-Cáceres
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D039441:Integrin alpha4 / Q000378:metabolism*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism*; D000069442:Natalizumab / Q000627:therapeutic use*; D011446:Prospective Studies; D012008:Recurrence
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D039441:Integrin alpha4
keywords: extended interval dosing; multiple sclerosis; natalizumab; quantitative flow cytometry; receptor occupancy; standard dose