Thompson J P, Noyes K, Dorsey E R, Schwid S R, Holloway R G
Department of Neurology, University of Rochester, Rochester, NY, USA.
Neurology. 2008 Jul 29;71(5):357-64. doi: 10.1212/01.wnl.0000319648.65173.7a.
To model the long-term risks and benefits of natalizumab in individuals with relapsing multiple sclerosis (MS).
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).
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%.
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.
对那他珠单抗用于复发型多发性硬化症（MS）患者的长期风险和益处进行建模。
我们创建了一个马尔可夫模型，利用已发表的自然病史数据和临床试验结果来评估其在减少复发和减缓疾病进展方面的治疗效果。以质量调整生命年（QALYs）衡量的健康变化基于患者的健康偏好。对未接受疾病修正治疗、使用那他珠单抗、皮下注射干扰素β-1a以及一种理论上的“完美”MS治疗的患者队列进行了建模。采用敏感性分析来探究模型的不确定性，包括发生进行性多灶性白质脑病（PML）的不同风险。
在20年的时间跨度内，使用那他珠单抗治疗可产生9.50个QALYs，比未治疗队列增加了0.80个QALYs，比干扰素β-1a增加了0.38个QALYs。PML导致的健康损失较小（-0.06个QALYs）。为抵消那他珠单抗相对于干扰素β-1a的额外健康获益，在17.9个月的治疗期内每1000例接受治疗的患者中，PML的风险必须从1例增加到7.6例。在20年的时间跨度内，“完美”的MS治疗累积了10.59个QALYs，比未治疗队列高出1.89个QALYs。如果那他珠单抗的相对复发减少率从68%降至35%，或者干扰素β-1a的相对减少率从32%提高到65%，那么与那他珠单抗相比，干扰素β-1a会带来更大的QALY增加。
要使那他珠单抗的健康获益低于干扰素β-1a，进行性多灶性白质脑病的实际风险需要增加7倍以上，并且在当前治疗已取得的健康获益基础上，仍有相当大的额外健康获益空间（>50%）。
