Abstract：
Neuropathic pain is common and difficult to treat. The sodium channel blocker lacosamide is efficacious in animal models of pain, but its effect on neuropathic pain in humans is inconclusive.
In a multicentre, randomized, double-blinded placebo-controlled phenotype stratified trial, we examined if lacosamide produced better pain relief in patients with the irritable nociceptor phenotype compared to those without. The primary outcome was the change in daily average pain from baseline to last week of 12 weeks of treatment. Secondary and tertiary outcomes included pain relief, patient global impression of change and presence of 30% and 50% pain reduction.
The study was prematurely closed with 93 patients included and 63 randomized to lacosamide or placebo in a 2:1 ratio, of which 49 fulfilled the per protocol criteria and was used for the primary objective. We did not find a better effect of lacosamide in patients with the irritable nociceptor phenotype, the 95% CI for the primary objective was 0.41 (-1.2 to 2.0). For all patients randomized, lacosamide had no effect on the primary outcome, but significantly more patients were responders to lacosamide than during placebo, with an NNT of 4.0 (95% CI 2.3-16.1) and 5.0 (95% CI 2.8-24.5) for 30% and 50% pain reduction respectively. We did not identify any predictors for response. Lacosamide was generally well tolerated.
We could not confirm that lacosamide was more efficacious in patients with the irritable nociceptor type, but the study was prematurely closed, so we cannot exclude a small difference.
Treatment of neuropathic pain is often a trial and error process. Little is known about which patient benefit from which kind of medication. The sodium channel blocker lacosamide shows variable effect on neuropathic pain. Pain sensory phenotype, as defined by quantitative sensory testing, did not predict response to treatment with lacosamide.
In a multicentre, randomized, double-blinded placebo-controlled phenotype stratified trial, we examined if lacosamide produced better pain relief in patients with the irritable nociceptor phenotype compared to those without. The primary outcome was the change in daily average pain from baseline to last week of 12 weeks of treatment. Secondary and tertiary outcomes included pain relief, patient global impression of change and presence of 30% and 50% pain reduction.
The study was prematurely closed with 93 patients included and 63 randomized to lacosamide or placebo in a 2:1 ratio, of which 49 fulfilled the per protocol criteria and was used for the primary objective. We did not find a better effect of lacosamide in patients with the irritable nociceptor phenotype, the 95% CI for the primary objective was 0.41 (-1.2 to 2.0). For all patients randomized, lacosamide had no effect on the primary outcome, but significantly more patients were responders to lacosamide than during placebo, with an NNT of 4.0 (95% CI 2.3-16.1) and 5.0 (95% CI 2.8-24.5) for 30% and 50% pain reduction respectively. We did not identify any predictors for response. Lacosamide was generally well tolerated.
We could not confirm that lacosamide was more efficacious in patients with the irritable nociceptor type, but the study was prematurely closed, so we cannot exclude a small difference.
Treatment of neuropathic pain is often a trial and error process. Little is known about which patient benefit from which kind of medication. The sodium channel blocker lacosamide shows variable effect on neuropathic pain. Pain sensory phenotype, as defined by quantitative sensory testing, did not predict response to treatment with lacosamide.
摘要：
背景：神经性疼痛是常见且难以治疗的。钠通道阻滞剂拉科酰胺在疼痛动物模型中有效，但它对人类神经性疼痛的影响尚无定论。
方法：在多中心中，随机化，双盲安慰剂对照表型分层试验，我们研究了与无刺激性痛觉感受器表型的患者相比,拉科沙胺是否能更好地缓解疼痛.主要结果是从基线到12周治疗最后一周的每日平均疼痛的变化。二级和三级结果包括疼痛缓解，患者的整体印象变化和存在30%和50%的疼痛减轻。
结果：该研究过早结束，纳入93例患者，63例以2:1的比例随机分配给拉科沙胺或安慰剂，其中49项符合符合方案标准并用于主要目标.我们没有发现拉科沙胺对易激伤害性感受器表型患者有更好的疗效，主要目标的95%CI为0.41(-1.2~2.0).对于所有随机分组的患者，拉科沙胺对主要结局没有影响，但与安慰剂组相比，更多的患者对拉科沙胺有反应，NNT分别为4.0（95％CI2.3-16.1）和5.0（95％CI2.8-24.5），疼痛减轻30％和50％。我们没有确定任何反应的预测因子。Lacosamide通常耐受良好。
结论：我们无法确认拉科沙胺在易激伤害性感受器型患者中更有效，但是这项研究过早结束了，所以我们不能排除一个小的差异。
结论：神经性疼痛的治疗通常是一个反复试验的过程。关于哪种患者受益于哪种药物，人们知之甚少。钠通道阻断剂拉科酰胺对神经性疼痛显示出不同的作用。疼痛感觉表型，根据定量感官测试的定义，无法预测对拉科沙胺治疗的反应。
方法：在多中心中，随机化，双盲安慰剂对照表型分层试验，我们研究了与无刺激性痛觉感受器表型的患者相比,拉科沙胺是否能更好地缓解疼痛.主要结果是从基线到12周治疗最后一周的每日平均疼痛的变化。二级和三级结果包括疼痛缓解，患者的整体印象变化和存在30%和50%的疼痛减轻。
结果：该研究过早结束，纳入93例患者，63例以2:1的比例随机分配给拉科沙胺或安慰剂，其中49项符合符合方案标准并用于主要目标.我们没有发现拉科沙胺对易激伤害性感受器表型患者有更好的疗效，主要目标的95%CI为0.41(-1.2~2.0).对于所有随机分组的患者，拉科沙胺对主要结局没有影响，但与安慰剂组相比，更多的患者对拉科沙胺有反应，NNT分别为4.0（95％CI2.3-16.1）和5.0（95％CI2.8-24.5），疼痛减轻30％和50％。我们没有确定任何反应的预测因子。Lacosamide通常耐受良好。
结论：我们无法确认拉科沙胺在易激伤害性感受器型患者中更有效，但是这项研究过早结束了，所以我们不能排除一个小的差异。
结论：神经性疼痛的治疗通常是一个反复试验的过程。关于哪种患者受益于哪种药物，人们知之甚少。钠通道阻断剂拉科酰胺对神经性疼痛显示出不同的作用。疼痛感觉表型，根据定量感官测试的定义，无法预测对拉科沙胺治疗的反应。
