title: Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy.
abstract: OBJECTIVE
  Natalizumab, a therapy for multiple sclerosis (MS), has been associated with progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection of the CNS associated with the JC virus. We assessed clinical outcomes and identified variables associated with survival in 35 patients with natalizumab-associated PML.
  
  
  METHODS
  Physicians provided Karnofsky scores and narrative descriptions of clinical status. Data were supplemented by the natalizumab global safety database.
  
  
  RESULTS
  At the time of analysis, 25 patients (71%) had survived. Survivors were younger (median 40 vs 54 years) and had lower pre-PML Expanded Disability Status Scale scores (median 3.5 vs 5.5) and a shorter time from symptom onset to diagnosis (mean 44 vs 63 days) compared with individuals with fatal cases. Of patients with nonfatal cases, 86% had unilobar or multilobar disease on brain MRI at diagnosis, whereas 70% of those with fatal cases had widespread disease. Gender, MS duration, natalizumab exposure, prior immunosuppressant use, and CSF JC viral load at diagnosis were comparable. Most patients were treated with rapid removal of natalizumab from the circulation. The majority of patients developed immune reconstitution inflammatory syndrome and were treated with corticosteroids. Among survivors with at least 6 months follow-up, disability levels were evenly distributed among mild, moderate, and severe, based on physician-reported Karnofsky scores.
  
  
  CONCLUSIONS
  Natalizumab-associated PML has improved survival compared with PML in other populations. Disability in survivors ranged from mild to severe. A shorter time from symptom onset to diagnosis and localized disease on MRI at diagnosis were associated with improved survival. These data suggest that earlier diagnosis through enhanced clinical vigilance and aggressive management may improve outcomes.
authors.affiliation: Department of Neurology, University of Lille Nord de France, Lille, France.
authors.forename: P
authors.initials: P
authors.lastname: Vermersch
authors.forename: L
authors.initials: L
authors.lastname: Kappos
authors.forename: R
authors.initials: R
authors.lastname: Gold
authors.forename: J F
authors.initials: JF
authors.lastname: Foley
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: D
authors.initials: D
authors.lastname: Cadavid
authors.forename: C
authors.initials: C
authors.lastname: Bozic
authors.forename: S
authors.initials: S
authors.lastname: Richman
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002423:Cause of Death; D004185:Disability Evaluation; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D007968:Leukoencephalopathy, Progressive Multifocal / Q000209:etiology* / Q000401:mortality; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy; D000069442:Natalizumab; D011237:Predictive Value of Tests; D011358:Product Surveillance, Postmarketing; D011379:Prognosis; D012959:Socioeconomic Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000069442:Natalizumab; D008942:Mitoxantrone