title: Natalizumab and progressive multifocal leukoencephalopathy: what are the causal factors and can it be avoided?
abstract: Natalizumab (Tysabri) was the first monoclonal antibody approved for the treatment of relapsing forms of multiple sclerosis (MS). After its initial approval, 3 patients undergoing natalizumab therapy in combination with other immunoregulatory and immunosuppressive agents were diagnosed with progressive multifocal leukoencephalopathy (PML). The agent was later reapproved and its use restricted to monotherapy in patients with relapsing forms of MS. Since reapproval in 2006, additional cases of PML were reported in patients with MS receiving natalizumab monotherapy. Thus, there is currently no convincing evidence that natalizumab-associated PML is restricted to combination therapy with other disease-modifying or immunosuppressive agents. In addition, recent data indicate that risk of PML might increase beyond 24 months of treatment.
authors.affiliation: Neurology Section, VA North Texas Health Care System, Medical Service, 4500 S Lancaster Rd, Dallas, TX 75216, USA.
authors.forename: Clemens
authors.initials: C
authors.lastname: Warnke
authors.forename: Til
authors.initials: T
authors.lastname: Menge
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Michael K
authors.initials: MK
authors.lastname: Racke
authors.forename: Petra D
authors.initials: PD
authors.lastname: Cravens
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Bennett
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Frohman
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Greenberg
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D039041:Integrin alpha4beta1 / Q000276:immunology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy* / Q000276:immunology*; D000069442:Natalizumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D039041:Integrin alpha4beta1; D000069442:Natalizumab