TY - JOUR
T1 - Quantitative risk-benefit analysis of natalizumab
AU - Thompson, J. P.
AU - Noyes, K.
AU - Dorsey, E. R.
AU - Schwid, S. R.
AU - Holloway, R. G.
PY - 2008/7/29
Y1 - 2008/7/29
N2 - 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 β-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 β-1a. The health loss due to PML was small (-0.06 QALYs). To offset natalizumab's incremental health gain over interferon β-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 β-1a resulted in greater QALY gains compared with natalizumab if natalizumab's relative relapse reduction was reduced from 68% to 35% or if interferon β-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 β-1a, and there remains considerable room for additional gains in health (>50%) beyond those already achieved with current therapies.
AB - 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 β-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 β-1a. The health loss due to PML was small (-0.06 QALYs). To offset natalizumab's incremental health gain over interferon β-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 β-1a resulted in greater QALY gains compared with natalizumab if natalizumab's relative relapse reduction was reduced from 68% to 35% or if interferon β-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 β-1a, and there remains considerable room for additional gains in health (>50%) beyond those already achieved with current therapies.
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U2 - 10.1212/01.wnl.0000319648.65173.7a
DO - 10.1212/01.wnl.0000319648.65173.7a
M3 - Article
C2 - 18663181
AN - SCOPUS:67649297820
SN - 0028-3878
VL - 71
SP - 357
EP - 364
JO - Neurology
JF - Neurology
IS - 5
ER -