Cardenas Diana D, Emir Birol, Parsons Bruce
Department of Physical Medicine & Rehabilitation, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida.
Pfizer Inc, New York, New York.
Clin Ther. 2015 May 1;37(5):1081-90. doi: 10.1016/j.clinthera.2015.02.028. Epub 2015 Apr 4.
In 2 large-scale, placebo-controlled trials, pregabalin improved both pain and pain-related sleep interference in patients with neuropathic pain due to spinal cord injury (SCI). In both trials, pregabalin found statistically significant improvement compared with placebo after 1 week of treatment. However, the effects of pregabalin in the days immediately after initiation of treatment are unknown. The purpose of the present analysis was to determine timing of pregabalin's therapeutic effect in the days after initiation of treatment.
Data were derived from 2 trials of pregabalin in patients with SCI-related neuropathic pain. Each day patients rated severity of pain and pain-related sleep interference over the past 24 hours on a scale from 0 to 10, with higher scores indicating greater severity. To quantify timing of therapeutic effect, we compared (pregabalin [vs] placebo) daily average pain and pain-related sleep interference scores over the first 14 days of treatment. Significant improvement was defined as the first day, of ≥2 consecutive days, that pregabalin significantly (P < 0.05) reduced mean scores compared with placebo. To further quantify timing of therapeutic effect, each treatment group was examined to determine the time required to achieve a ≥1-point improvement in pain and pain-related sleep interference score among patients with a clinically meaningful and sustained response (≥30% improvement from baseline to end point) by using a time-to-event analysis method. Kaplan-Meier analyses were used to estimate the median (or 25th quartile) time (in days) required to achieve a ≥1-point improvement, among these responders, in pain and pain-related sleep interference scores. Comparisons between pregabalin and placebo were made with a log-rank test.
In both trials, significant improvement of pain and pain-related sleep interference occurred within 2 days of initiating treatment with pregabalin. Among patients reporting a clinically meaningful and sustained response to treatment (patients with ≥30% improvement from baseline to end point), the time to a ≥1-point improvement of pain and pain-related sleep interference occurred significantly earlier among pregabalin-treated patients than among placebo-treated patients. Finally, the timing of pregabalin's effect on pain and pain-related sleep interference was unaffected by the use of concomitant medications that were allowed for treatment of neuropathic pain in both trials.
Treatment with pregabalin results in rapid time to significant improvement in both pain and pain-related sleep interference in patients with neuropathic pain due to SCI. These findings should only be used as a guide to physicians and patients as to when clinical response to pregabalin may be expected.
在两项大规模、安慰剂对照试验中，普瑞巴林改善了脊髓损伤（SCI）所致神经性疼痛患者的疼痛及与疼痛相关的睡眠干扰。在这两项试验中，治疗1周后，与安慰剂相比，普瑞巴林在统计学上有显著改善。然而，普瑞巴林在治疗开始后即刻的效果尚不清楚。本分析的目的是确定普瑞巴林在治疗开始后数天内的治疗效果出现时间。
数据来源于两项普瑞巴林治疗SCI相关性神经性疼痛患者的试验。患者每天对过去24小时内的疼痛严重程度及与疼痛相关的睡眠干扰进行评分，范围为0至10分，分数越高表明严重程度越高。为了量化治疗效果出现时间，我们比较了治疗前14天内普瑞巴林组与安慰剂组的每日平均疼痛及与疼痛相关的睡眠干扰评分。显著改善定义为普瑞巴林组与安慰剂组相比，连续至少2天平均评分显著降低（P < 0.05）的第一天。为进一步量化治疗效果出现时间，通过生存分析方法，对每个治疗组进行检查，以确定在有临床意义且持续应答（从基线到终点改善≥30%）的患者中，疼痛及与疼痛相关的睡眠干扰评分提高≥1分所需的时间。采用Kaplan-Meier分析估计这些应答者中疼痛及与疼痛相关的睡眠干扰评分提高≥1分所需的中位（或第25百分位数）时间（天数）。用对数秩检验对普瑞巴林组和安慰剂组进行比较。
在两项试验中，使用普瑞巴林治疗后2天内，疼痛及与疼痛相关的睡眠干扰均有显著改善。在报告对治疗有临床意义且持续应答的患者（从基线到终点改善≥30%的患者）中，普瑞巴林治疗组患者疼痛及与疼痛相关的睡眠干扰评分提高≥1分的时间显著早于安慰剂治疗组患者。最后，普瑞巴林对疼痛及与疼痛相关的睡眠干扰的作用时间不受两项试验中允许用于治疗神经性疼痛的伴随用药的影响。
普瑞巴林治疗可使SCI所致神经性疼痛患者的疼痛及与疼痛相关的睡眠干扰迅速得到显著改善。这些发现仅可作为医生和患者预测对普瑞巴林临床应答时间的参考。
