Quantitative risk-benefit analysis of natalizumab.
OBJECTIVE
To model the long-term risks and benefits of natalizumab in individuals with relapsing multiple sclerosis (MS).


METHODS
We created a Markov model to evaluate treatment effects on reducing relapses and slowing disease progression using published natural history data and clinical trial results. Health changes, measured in quality-adjusted life-years (QALYs), were based on patient health preferences. Patient cohorts treated with no disease-modifying treatment, natalizumab, subcutaneous interferon beta-1a, and a theoretical "perfect" MS treatment were modeled. Sensitivity analysis was used to explore model uncertainty, including varying risks of developing progressive multifocal leukoencephalopathy (PML).


RESULTS
Treatment with natalizumab resulted in 9.50 QALYs over a 20-year time horizon, a gain of 0.80 QALYs over the untreated cohort and 0.38 QALYs over interferon beta-1a. The health loss due to PML was small (-0.06 QALYs). To offset natalizumab's incremental health gain over interferon beta-1a, the risk had to increase from 1 to 7.6 PML per 1,000 patients treated over 17.9 months. The "perfect" MS treatment accumulated 10.59 QALYs over the 20-year time horizon, 1.89 QALYs above the untreated cohort. Interferon beta-1a resulted in greater QALY gains compared with natalizumab if natalizumab's relative relapse reduction was reduced from 68% to 35% or if interferon beta-1a's relative reduction was increased from 32% to 65%.


CONCLUSIONS
A more than sevenfold increase in actual risk of progressive multifocal leukoencephalopathy was required to decrease natalizumab's health gain below that of interferon beta-1a, and there remains considerable room for additional gains in health (>50%) beyond those already achieved with current therapies.
Thompson
J P
JP
Department of Neurology, University of Rochester, Rochester, NY, USA.
Noyes
K
K
Dorsey
E R
ER
Schwid
S R
SR
Holloway
R G
RG
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D008390:Markov Chains; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D000069442:Natalizumab; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D018570:Risk Assessment; D040242:Risk Reduction Behavior; D055502:Secondary Prevention; D013995:Time; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab; D016899:Interferon-beta; D000068556:Interferon beta-1a