title: A benefit-risk analysis of natalizumab in the treatment of patients with multiple sclerosis when considering the risk of progressive multifocal leukoencephalopathy.
abstract: BACKGROUND
  Natalizumab is a highly effective treatment for patients with relapsing-remitting multiple sclerosis (RRMS). Treatment with natalizumab has been associated with progressive multifocal leukoencephalopathy (PML), a rare yet serious disease of the brain. Published studies have quantified the PML risk by the presence of anti-JC virus antibodies, previous immunosuppressant use, and duration of natalizumab treatment.
  
  
  OBJECTIVE
  The aim of this analysis was to evaluate the net benefits and risks for patients with RRMS receiving natalizumab treatment compared with fingolimod, interferon-β, and no treatment across PML risk sub-groups.
  
  
  METHODS
  Based on previously validated MS model structures, a Markov cohort model was developed to assess the impact of treatment on quality-adjusted life years (QALYs). Natalizumab-treated patients were classified by PML risk sub-groups and analysed separately for short-term (2 years) and long-term (20 years) time horizons.
  
  
  METHODS
  Main outcome measures included total QALYs by PML risk sub-group and the increase in PML risk associated with natalizumab treatment which offsets the quality of life benefit of comparator treatments.
  
  
  RESULTS
  Results showed higher QALYs with natalizumab versus all other comparators across PML risk sub-groups over both time horizons. For the QALYs of natalizumab to equal the QALYs of fingolimod, interferon-β, and no treatment, the risk of PML would have to increase 4.6-84.2 times, 24.0-444.3 times, and 5.7-106.1 times, respectively (short term), and 1.4-123.4 times, 1.5-138.3 times, and 2.2-193.7 times, respectively (long term).
  
  
  CONCLUSIONS
  This study shows that natalizumab generates the most net health benefits in terms of quality-adjusted life years compared with fingolimod, interferon-β, or no treatment, even when the risk of natalizumab-associated PML is taken into consideration. This study is limited by the availability of published data around natalizumab-associated PML, as well as the constraints of the model used to conduct the analysis.
authors.affiliation: Heron Evidence Development Ltd , London , UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Walker
authors.forename: Crystal
authors.initials: C
authors.lastname: Watson
authors.forename: Stamatia T
authors.initials: ST
authors.lastname: Alexopoulos
authors.forename: Baris
authors.initials: B
authors.lastname: Deniz
authors.forename: Ryan
authors.initials: R
authors.lastname: Arnold
authors.forename: David
authors.initials: D
authors.lastname: Bates
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab; D019057:Quality-Adjusted Life Years; D012306:Risk
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab