title: Does risk stratification decrease the risk of natalizumab-associated PML? Where is the evidence?
abstract: The use of natalizumab has likely been limited by its association with progressive multifocal leukoencephalopathy (PML), an infection caused by the human polyomavirus John Cunningham (JC). Three factors were recently identified that contribute to the overall risk of natalizumab-associated PML: (1) Positive serostatus for anti-JCV antibodies, (2) prior use of immunosuppressants, and (3) duration of natalizumab therapy. This risk stratification algorithm has not led to a reduction in the incidence of PML in natalizumab-treated patients with multiple sclerosis between April 2010 and February 2014. This observation may appear perplexing, as treatment duration and JCV serostatus are modifiable risk factors. Potential reasons for the lack of success of companion diagnostics that determine the overall risk of natalizumab-associated PML are discussed.
authors.affiliation: Section on Research Methods and Clinical Trials, University of Alabama at Birmingham, Birmingham, USA.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
authors.affiliation: VA North Texas Health Care System, Medical Service Dallas, VA Medical Center/University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA/Klinikum rechts der Isar, Technische Universität München, Germany olaf.stuve@utsouthwestern.edu.
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
mesh_terms: D000465:Algorithms; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D003661:Decision Support Techniques; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007577:JC Virus / Q000276:immunology / Q000472:pathogenicity; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab; D018579:Patient Selection; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069442:Natalizumab
keywords: Disease-modifying therapies; multiple sclerosis; outcome measurement