Epilepsy Research Group, Berlin, Germany.
Epilepsy Behav. 2013 May;27(2):393-8. doi: 10.1016/j.yebeh.2013.01.015. Epub 2013 Mar 13.
For clinical trial design and for clinical practice, it is of importance to assess factors associated with placebo response in patients with refractory epilepsy. We determined factors associated with placebo response in 359 adult patients with refractory focal epilepsy participating in three randomized placebo-controlled trials of the new antiepileptic drug lacosamide. At the end of the randomized 12-week maintenance period, 81 (23%) of the 359 patients randomized to placebo achieved at least a 50% seizure reduction (responders) compared to baseline. In contrast, 278 (77%) patients did not achieve a 50% seizure reduction (non-responders) compared to baseline. In multivariate analysis, five factors, which were present prior to the exposure to placebo, were found to be associated with placebo response. Higher age at study entry improved the chances of placebo response for each year [p=0.023, odds ratio (OR) 1.034 (95% confidence interval (95% CI): 1.005-1.063)]. In contrast, a lower chance of placebo response was seen with age at diagnosis of epilepsy of 6-20 years compared to ≤5 years [p=0.041, OR 0.475 (95% CI: 0.232-0.971)]. A history of 7 or more prior lifetime AEDs lowered the chance of achieving placebo response compared to 1-3 prior lifetime AEDs [p<0.001, OR 0.224 (95% CI: 0.101-0.493)] as did a baseline seizure frequency >10 seizures per 28 days compared to ≤5 seizures per 28 days [p=0.026, OR 0.431 (95% CI: 0.205-0.904)]. Prior epilepsy surgery lowered the likelihood of placebo response [p=0.02, OR 0.22 (95% CI: 0.062-0.785)]. We suggest that age at exposure to placebo, age at diagnosis of epilepsy, the number of prior lifetime AEDs, baseline seizure frequency and a history of epilepsy surgery appear to be associated with placebo response in adults with refractory focal epilepsy.
对于临床研究设计和临床实践来说，评估难治性癫痫患者中与安慰剂反应相关的因素非常重要。我们确定了 359 名接受新抗癫痫药物拉科酰胺的随机安慰剂对照试验的难治性局灶性癫痫成年患者中与安慰剂反应相关的因素。在随机的 12 周维持期结束时，与基线相比，359 名随机接受安慰剂的患者中有 81 名（23%）至少实现了 50%的癫痫发作减少（应答者）。相比之下，278 名（77%）患者与基线相比没有实现 50%的癫痫发作减少（无应答者）。在多变量分析中，发现五个在接触安慰剂之前存在的因素与安慰剂反应相关。研究时的年龄每增加一年，安慰剂反应的机会就会增加[P=0.023，优势比（OR）为 1.034（95%置信区间（95%CI）：1.005-1.063）]。相比之下，与≤5 岁相比，癫痫诊断年龄为 6-20 岁的患者，安慰剂反应的机会较低[P=0.041，OR 0.475（95%CI：0.232-0.971）]。与≤3 种既往终生抗癫痫药（AED）相比，7 种或更多既往终生 AED 降低了达到安慰剂反应的机会[P<0.001，OR 0.224（95%CI：0.101-0.493）]，基线发作频率>10 次/28 天与≤5 次/28 天相比也是如此[P=0.026，OR 0.431（95%CI：0.205-0.904）]。既往癫痫手术降低了安慰剂反应的可能性[P=0.02，OR 0.22（95%CI：0.062-0.785）]。我们认为，接触安慰剂时的年龄、癫痫诊断时的年龄、既往终生 AED 的数量、基线发作频率和癫痫手术史似乎与成年难治性局灶性癫痫患者的安慰剂反应相关。
