Ueberall Michael A, Mueller-Schwefe Gerhard H H
Institute of Neurological Sciences, Nuernberg, Germany.
Interdisciplinary Center for Pain and Palliative Care Medicine, Goeppingen, Germany.
J Pain Res. 2016 Nov 11;9:1001-1020. doi: 10.2147/JPR.S112418. eCollection 2016.
To evaluate the benefit-risk profile (BRP) of oxycodone/naloxone (OXN) and tapentadol (TAP) in patients with chronic low back pain (cLBP) with a neuropathic component (NC) in routine clinical practice.
This was a blinded end point analysis of randomly selected 12-week routine/open-label data of the German Pain Registry on adult patients with cLBP-NC who initiated an index treatment in compliance with the current German prescribing information between 1st January and 31st October 2015 (OXN/TAP, n=128/133). Primary end point was defined as a composite of three efficacy components (≥30% improvement of pain, pain-related disability, and quality of life each at the end of observation vs baseline) and three tolerability components (normal bowel function, absence of either central nervous system side effects, and treatment-emergent adverse event [TEAE]-related treatment discontinuation during the observation period) adopted to reflect BRP assessments under real-life conditions.
Demographic as well as baseline and pretreatment characteristics were comparable for the randomly selected data sets of both index groups without any indicators for critical selection biases. Treatment with OXN resulted formally in a BRP noninferior to that of TAP and showed a significantly higher primary end point response vs TAP (39.8% vs 25.6%, odds ratio: 1.93; =0.014), due to superior analgesic effects. Between-group differences increased with stricter response definitions for all three efficacy components in favor of OXN: ≥30%/≥50%/≥70% response rates for OXN vs TAP were seen for pain intensity in 85.2%/67.2%/39.1% vs 83.5%/54.1%/15.8% (= ns/0.031/<0.001), for pain-related disability in 78.1%/64.8%/43.8% vs 66.9%/50.4%/24.8% (=0.043/0.018/0.001), and for quality of life in 76.6%/68.0%/50.0% vs 63.9%/54.1%/34.6% (=0.026/0.022/0.017). Overall, OXN vs TAP treatments were well tolerated, and proportions of patients who either maintained a normal bowel function (68.0% vs 72.2%), reported no central nervous system side effects (91.4% vs 89.5%), or completed the 12-week evaluation period without any TEAE-related treatment discontinuations (93.0% vs 92.5%) were similar for both index medications (= ns for each comparison).
In daily practice, the BRP of OXN proved to be noninferior to that of TAP in patients with cLBP-NC, but showed a superior efficacy if stricter analgesic response definitions were evaluated.
在常规临床实践中，评估羟考酮/纳洛酮（OXN）和曲马多（TAP）对伴有神经病理性成分（NC）的慢性下腰痛（cLBP）患者的获益-风险概况（BRP）。
这是一项对德国疼痛登记处2015年1月1日至10月31日期间符合现行德国处方信息开始进行索引治疗的成年cLBP-NC患者的随机选择的12周常规/开放标签数据进行的盲终点分析（OXN/TAP，n = 128/133）。主要终点定义为三个疗效成分（观察结束时与基线相比疼痛改善≥30%、疼痛相关残疾改善≥30%、生活质量改善≥30%）和三个耐受性成分（正常肠功能、无中枢神经系统副作用、观察期内无治疗引发的不良事件[TEAE]相关治疗中断）的综合指标，用于反映现实生活条件下的BRP评估。
两个索引组随机选择的数据集的人口统计学以及基线和预处理特征具有可比性，没有任何关键选择偏倚的指标。OXN治疗在形式上导致BRP不劣于TAP，并且由于更好的镇痛效果，其主要终点反应显著高于TAP（39.8%对25.6%，优势比：1.93；P = 0.014）。随着对所有三个疗效成分采用更严格的反应定义，组间差异增大，更有利于OXN：OXN与TAP相比，疼痛强度≥30%/≥50%/≥70%的反应率分别为85.2%/67.2%/39.1%对83.5%/54.1%/15.8%（P = 无显著性差异/0.031/<0.001），疼痛相关残疾分别为78.1%/64.8%/43.8%对66.9%/50.4%/24.8%（P = 0.043/0.018/0.001），生活质量分别为76.6%/68.0%/50.0%对63.9%/54.1%/34.6%（P = 0.026/0.022/0.017）。总体而言，OXN与TAP治疗耐受性良好，两种索引药物在维持正常肠功能的患者比例（68.0%对72.2%）、报告无中枢神经系统副作用的患者比例（91.4%对89.5%）或在无任何TEAE相关治疗中断的情况下完成12周评估期的患者比例（93.0%对92.5%）方面相似（每项比较P = 无显著性差异）。
在日常实践中，对于cLBP-NC患者，OXN的BRP被证明不劣于TAP，但如果评估更严格的镇痛反应定义，则显示出更好的疗效。
