Phase I/II parallel double-blind randomized controlled clinical trial of perispinal etanercept for chronic stroke

Background: Previous open-label studies showed that chronic post-stroke pain could be abated by treatment with perispinal etanercept, although these benefits were questioned. A randomized double-blind placebo controlled clinical trial was conducted to test perispinal etanercept for chronic post-stroke pain. Research design and methods: Participants received two treatments, either perispinal etanercept (active) or saline (control). Primary outcomes were the differences in daily pain levels between groups analyzed by SPSS. Results: On the 0–100 points visual analog scale, perispinal etanercept reduced mean levels for worst and average daily pain from baseline after two treatments by 19.5 – 24 points (p < 0.05), and pain alleviation was maintained in the etanercept group, with no significant change in the control group. Thirty percent of etanercept participants had near complete pain abatement after first treatment. Goniometry of the paretic arm showed improved mean shoulder rotation by 55 degrees in active forward flexion for the etanercept group (p = 0.003) only. Conclusions: Perispinal etanercept can provide significant and ongoing benefits for the chronic poststroke management of pain and greater shoulder flexion by the paretic arm. Effects are rapid and highly significant, supporting direct action on brain function. Trial registration: ACTRN12615001377527 and Universal Trial Number U1111-1174-3242.

背景：既往开放标签研究显示，脊柱旁给予依那西普（perispinal etanercept）可缓解慢性卒中后疼痛，但该治疗获益曾受到质疑。为此本研究开展了一项随机双盲安慰剂对照临床试验，以评估脊柱旁依那西普治疗慢性卒中后疼痛的效果。
研究设计与方法：受试者接受两次治疗，分别为脊柱旁依那西普（活性组）或生理盐水（对照组）。主要终点指标为两组每日疼痛水平的差异，采用SPSS软件进行统计分析。
结果：在0~100分视觉模拟评分法（visual analog scale, VAS）中，两次治疗后，脊柱旁依那西普组患者的日常最严重疼痛及平均疼痛的平均得分较基线降低19.5~24分（p<0.05）；依那西普组的疼痛缓解效应持续维持，而对照组未出现显著变化。30%的依那西普组受试者在首次治疗后即实现接近完全的疼痛缓解。对偏瘫侧上肢进行关节角度测量显示，仅依那西普组患者的肩部主动前屈平均活动度较基线改善55度（p=0.003）。
结论：脊柱旁依那西普可显著且持续地改善慢性卒中后疼痛管理，并提升偏瘫侧上肢的肩部屈曲活动度。该治疗起效迅速且效应显著，提示其可直接作用于脑功能。
试验注册编号：ACTRN12615001377527 及通用试验编号U1111-1174-3242。