From Harvard-MIT Health Sciences and Technology (E.L.B., L.-Y.C., P.N.), Harvard Medical School; and Department of Neurology (L.M.V.R.M., A.J.C., S.S.C., D.B.H., M.T.B., M.B.W.), Massachusetts General Hospital, Boston.
Neurology. 2018 Oct 9;91(15):e1429-e1439. doi: 10.1212/WNL.0000000000006319. Epub 2018 Sep 12.
To compare the expected quality-adjusted life-years (QALYs) in adult patients undergoing immediate vs deferred antiepileptic drug (AED) treatment after a first unprovoked seizure.
We constructed a simulated clinical trial (Markov decision model) to compare immediate vs deferred AED treatment after a first unprovoked seizure in adults. Three base cases were considered, representing patients with varying degrees of seizure recurrence risk and effect of seizures on quality of life (QOL). Cohort simulation was performed to determine which treatment strategy would maximize the patient's expected QALYs. Sensitivity analyses were guided by clinical data to define decision thresholds across plausible measurement ranges, including seizure recurrence rate, effect of seizure recurrence on QOL, and efficacy of AEDs.
For patients with a moderate risk of recurrent seizures (52.0% over 10 years after first seizure), immediate AED treatment maximized QALYs compared to deferred treatment. Sensitivity analyses showed that for the preferred choice to change to deferred AED treatment, key clinical measures needed to reach implausible values were 10-year seizure recurrence rate ≤38.0%, QOL reduction with recurrent seizures ≤0.06, and efficacy of AEDs on lowering seizure recurrence rate ≤16.3%.
Our model determined that immediate AED treatment is preferable to deferred treatment in adult first-seizure patients over a wide and clinically relevant range of variables. Furthermore, our analysis suggests that the 10-year seizure recurrence rate that justifies AED treatment (38.0%) is substantially lower than the 60% threshold used in the current definition of epilepsy.
比较首次无诱因发作后立即与延迟使用抗癫痫药物（AED）治疗的成年患者的预期质量调整生命年（QALY）。
我们构建了一个模拟临床试验（Markov 决策模型），以比较成人首次无诱因发作后立即与延迟使用 AED 治疗。考虑了三种基本情况，分别代表具有不同复发风险和癫痫对生活质量（QOL）影响程度的患者。通过队列模拟确定哪种治疗策略可以最大限度地提高患者的预期 QALY。敏感性分析根据临床数据指导，以确定决策阈值在合理的测量范围内的变化，包括癫痫复发率、癫痫复发对 QOL 的影响以及 AED 的疗效。
对于具有中度癫痫复发风险的患者（首次发作后 10 年内复发率为 52.0%），与延迟治疗相比，立即使用 AED 治疗可使 QALY 最大化。敏感性分析表明，为了改变为延迟 AED 治疗的首选治疗方案，需要达到不合理值的关键临床措施是 10 年癫痫复发率≤38.0%、癫痫复发导致 QOL 降低≤0.06 和 AED 降低癫痫复发率的疗效≤16.3%。
我们的模型确定，在广泛且具有临床意义的变量范围内，与延迟治疗相比，立即使用 AED 治疗对成年首次发作患者更为有利。此外，我们的分析表明，支持 AED 治疗的 10 年癫痫复发率（38.0%）远低于当前癫痫定义中使用的 60%阈值。
