Butler Stephen, Eek Daniel, Ring Lena, Gordon Allen, Karlsten Rolf
University Hospital, Pain Center, ING 79, 2 TR, Uppsala 75185, Sweden.
Department of Family Medicine and Public Health, Uppsala University, Uppsala, Sweden, Phone: +46 18 6110110, Fax: +46 18 503539.
Scand J Pain. 2019 Apr 24;19(2):327-335. doi: 10.1515/sjpain-2018-0317.
Background and aims The RELIEF (Real Life) study by AstraZeneca was designed as an observational study to validate a series of Patient Reported Outcome (PRO) questionnaires in a mixed population of subjects with neuropathic pain (NP) coming from diabetes, neurology and primary care clinics. This article is an analysis of a subset of the information to include the medications used and the effects of pharmacological treatment over 6 months. The RELIEF study was performed during 2010-2013. Methods Subjects were recruited from various specialty clinics and one general practice clinic across Canada. The subjects were followed for a total of 2 years with repeated documentation of their status using 10 PROs. A total of 210 of the recruited subjects were entered into the data base and analyzed. Of these, 123 had examination-verified painful diabetic neuropathy (PDN) and 87 had examination-verified post-traumatic neuropathy (PTN). To evaluate the responsiveness of the PROs to change, several time points were included and this study focusses primarily on the first 6 months. Subjects also maintained a diary to document all medications, both for pain and other medical conditions, including all doses, start dates and stop dates, that could be correlated to changes in the PRO parameters. Results RELIEF was successful in being able to correlate the validity of the PROs and this data was used for further AstraZeneca Phase 1, 2, and 3 clinical trials of NP. To our surprise, there was very little change in pain and low levels of patient satisfaction with treatment during the trial. Approximately 15% of the subjects reported improvement, 8% worsening of pain, the remainder reported pain unchanged despite the use of multiple medications at multiple doses, alone or in combination with frequent changes of medications and doses over the study. Those taking predominantly NSAIDs (COX-inhibitors) did no worse than those taking the standard recommended medications against NP. Conclusions Since this is a real-life study, it reflects the clinical utility of a variety of internationally recommended medications for the treatment of NP. In positive clinical trials of these medications in selected "ideal" subjects, the effects are not overwhelming - 30% are 50% improved on average. This study shows that in the real world the results are not nearly as positive and reflects information from non-published negative clinical trials. Implications We still do not have very successful medications for NP. Patients probably differ in many respects from those subjects in clinical trials. This is not to negate the use of recommended medications for NP but an indication that success rates of treatment are likely to be worse than the data coming from those trials published by the pharmaceutical industry.
背景与目的 阿斯利康公司开展的RELIEF（真实生活）研究旨在进行一项观察性研究，以在来自糖尿病、神经病学和初级保健诊所的患有神经性疼痛（NP）的混合人群中验证一系列患者报告结局（PRO）问卷。本文是对一部分信息的分析，内容包括所使用的药物以及6个月内药物治疗的效果。RELIEF研究于2010年至2013年期间进行。方法 研究对象从加拿大各地的多个专科诊所和一家全科诊所招募。对研究对象进行了为期2年的随访，使用10种PRO反复记录他们的状况。共有210名招募的研究对象被录入数据库并进行分析。其中，123人经检查确诊为疼痛性糖尿病神经病变（PDN），87人经检查确诊为创伤后神经病变（PTN）。为了评估PRO对变化的反应性，纳入了几个时间点，本研究主要关注前6个月。研究对象还记录日记，记录所有用于止痛和其他医疗状况的药物，包括所有剂量、开始日期和停药日期，这些信息可与PRO参数的变化相关联。结果 RELIEF成功地关联了PRO的有效性，这些数据被用于阿斯利康公司进一步开展的NP的1期、2期和3期临床试验。令我们惊讶的是，在试验期间疼痛变化很小，患者对治疗的满意度较低。大约15%的研究对象报告疼痛有所改善，8%报告疼痛加重，其余研究对象报告尽管在研究期间单独或联合使用了多种药物且频繁改变药物和剂量，但疼痛未变。主要服用非甾体抗炎药（COX抑制剂）的患者并不比服用标准推荐的抗NP药物的患者情况更差。结论 由于这是一项真实生活研究，它反映了多种国际推荐药物治疗NP的临床效用。在这些药物针对选定的“理想”研究对象进行的阳性临床试验中，效果并不显著——平均30%至50%的患者有所改善。本研究表明，在现实世界中结果并非如此乐观，这反映了未发表的阴性临床试验的信息。启示 我们仍然没有非常成功的治疗NP的药物。患者在许多方面可能与临床试验中的研究对象不同。这并非否定使用推荐的NP药物，而是表明治疗成功率可能比制药行业发表的那些试验数据更差。
