A benefit-risk analysis of natalizumab in the treatment of patients with multiple sclerosis when considering the risk of progressive multifocal leukoencephalopathy

Curr Med Res Opin. 2014 Apr;30(4):629-35. doi: 10.1185/03007995.2013.869492. Epub 2013 Dec 5.


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.

Objectives: 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.

Research design and 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.

Main outcome measures: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Humans
  • Leukoencephalopathy, Progressive Multifocal / chemically induced*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Natalizumab
  • Quality-Adjusted Life Years
  • Risk


  • Antibodies, Monoclonal, Humanized
  • Natalizumab