title: Progressive multifocal leukoencephalopathy in patients with systemic lupus erythematosus: a systematic literature review.
abstract: OBJECTIVE
  To determine risk factors for progressive multifocal leukoencephalopathy (PML) in systemic lupus erythematosus (SLE) patients, and understand how underlying disease or treatment for SLE may be associated with PML in this population.
  
  
  METHODS
  Studies published in English between January 1, 1984 and October 31, 2014 that reported PML in adult SLE patients were included. Immunosuppression was defined as exposure to ≥1 immunosuppressant drug of interest at PML diagnosis: belimumab, rituximab, mycophenolate mofetil, azathioprine, cyclophosphamide, methotrexate and high-dose corticosteroids (>15 mg/day). Minimal immunosuppression was defined as low-dose corticosteroids (≤15 mg/day) and/or anti-malarials.
  
  
  RESULTS
  Thirty-five publications met our inclusion criteria: four observational studies, two large case series, and 29 case reports that described 35 cases. Reported PML incidence rates among SLE patients based on observational studies ranged from 1.0 to 2.4 cases/100,000 person-years. Of the 35 case reports, three cases were exposed to no immunosuppressant drugs at PML diagnosis, five cases had minimal immunosuppression, 23 cases had immunosuppression, and four cases were indeterminate.
  
  
  CONCLUSIONS
  The evidence from this literature review suggests that, while PML is a very rare disease in SLE patients, there does appear to be an increased risk of PML associated with SLE compared to the general population, potentially due to immunosuppression, other contributing factors in their underlying disease, treatments prescribed to manage disease, or some combination of these factors. Additional large observational studies, designed to assess exposure to drugs of interest and complicated treatment histories, are needed to provide further evidence about potential mechanisms contributing to the onset of PML in SLE patients.
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, USA cehenegar@gmail.com.
authors.forename: C E
authors.initials: CE
authors.lastname: Henegar
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, USA Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Eudy
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, USA.
authors.forename: V
authors.initials: V
authors.lastname: Kharat
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Hill
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, USA.
authors.forename: D
authors.initials: D
authors.lastname: Bennett
authors.affiliation: Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Research Triangle Park, USA.
authors.forename: B
authors.initials: B
authors.lastname: Haight
mesh_terms: D000328:Adult; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007968:Leukoencephalopathy, Progressive Multifocal / Q000453:epidemiology / Q000209:etiology*; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents
keywords: Progressive multifocal leukoencephalopathy; immunosuppressant medications; monoclonal antibodies; systemic lupus erythematosus