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.

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.

• Authors: Anna Walker, Crystal Watson, Stamatia T Alexopoulos, Baris Deniz, Ryan Arnold, David Bates
• Journal: Current medical research and opinion (Curr Med Res Opin) Vol. 30 Issue 4 Pg. 629-35 (Apr 2014) ISSN: 1473-4877 [Electronic] England
• PMID: 24289170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Natalizumab

Topics

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