A sequenced-strategy for improving outcomes in patients with knee osteoarthritis pain

项目概要/摘要 膝关节骨关节炎（KOA）是全球慢性疼痛和残疾的主要原因之一， 30%的老年人，是个人和社会的主要全球健康和经济负担。的 在过去的70年里，KOA的发病率增加了一倍多，并且随着寿命的增加， 预期寿命和人口BMI。手术常用于治疗KOA，但其与高发病率相关。 持续的疼痛，并不是一个永久的解决方案。许多非手术疗法已被提倡， 治疗KOA患者的疼痛。然而，包括非阿片类药物在内的独立保守治疗 药物治疗和关节注射只能有限地缓解膝关节亚组的疼痛和改善功能。 OA患者。这导致这一人群中阿片类药物的使用率很高。本提案的总体目标是 是进行一项序贯平行组随机对照试验（RCT），以严格评估 保守行为和非阿片类药物治疗的比较有效性（I期） 以及在无应答者中，非手术程序干预（II期）在三个间期的获益- 相关目标。目标1将评估个人和联合在线认知行为的有效性 治疗（PainTRAINER）和药物治疗（度洛沙汀）改善KOA疼痛和功能 与标准治疗相比，目的2将确定膝神经射频消融（RFA） 或关节内注射透明质酸和类固醇比局部注射更有效地改善结果 麻醉神经阻滞或SOC，并帮助建立这些介入治疗在整体 KOA患者的疼痛管理。I期治疗失败的患者将获得 阿片类药物用于严重疼痛管理，如果合适的话，使我们能够检查这些药物的阿片类药物节省效果。 参与者的子集中的程序。目标3将测试临床和心理社会表型是否预测 短期和长期治疗反应。我们的研究涉及全面和创新的方法， 我以前从未在这种情况下被雇用，包括：一个多学科的调查骨干 进行迄今为止最大的随机试验，评估行为，药物治疗和非手术治疗， KOA的程序干预;一个阶梯式护理，析因设计模型，允许20多个 成对治疗比较;表型分析以确定应答者并改善每种治疗的选择 (i.e.精准医疗），预计将改善结果并减少不必要的干预。的 成果将遵循务实原则，以便最大限度地向利益攸关方提供信息， 不仅检查每项测试干预措施的有效性，而且还提供有意义的信息 关于关键患者亚组的有效性。获得的知识将有助于 开发可翻译的治疗策略，用于治疗KOA疼痛患者， 阿片类药物的节省作用。

PROJECT SUMMARY/ABSTRACT Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and disability worldwide, affecting over 30% of older adults and represents a major global health and economic burden to individuals and society. The rates of KOA have more than doubled in the past 70 years and continue to grow sharply, given increases in life expectancy and population BMI. Surgery is often employed to treat KOA, but it associated with a high rate of persistent pain, and is not a permanent solution. Numerous nonsurgical therapies have been advocated to treat pain in patients with KOA. However, stand-alone conservative treatments including non-opioid medications and joint injections provide only limited pain relief and functional improvement in a subset of knee OA sufferers. This has led to a high rate of opioid use in this population. The overarching goal of this proposal is to conduct a sequential parallel group randomized controlled trial (RCT) to rigorously evaluate the comparative-effectiveness of conservative behavioral and non-opioid pharmacological treatments (Phase I) and, among non-responders, the benefits of nonsurgical procedural interventions (Phase II) in three inter- related Aims. Aim 1 will evaluate the effectiveness of individual and combined online cognitive behavioral therapy (PainTRAINER) and pharmacologic treatment (duloxetine) in improving pain and function for KOA patients compared to standard of care. Aim 2 will determine if genicular nerve radiofrequency ablation (RFA) or intra-articular injection of hyaluronic acid and steroid are more effective in improving outcomes than local anesthetic nerve block or SOC and help establish the role of these interventional treatments in the overall management of pain in KOA patients. Patients that have failed Phase I treatment will be provided with an opioid for severe pain management, if appropriate, allowing us to examine the opioid-sparing effects of these procedures in a subset of participants. Aim 3 will test whether clinical and psychosocial phenotypes predict short- and long-term treatment response. Our study involves comprehensive and innovative approaches that have never before been employed in this context, including: a multidisciplinary cadre of investigators conducting the largest randomized trial to date evaluating behavioral, pharmacotherapy and nonsurgical procedural interventions for KOA; a stepped-care, factorial design model that allows for more than two dozen pair-wise treatment comparisons; phenotyping to identify responders and improve selection for each therapy (i.e. precision medicine), which is expected to refine outcomes and reduce unnecessary interventions. The results, which will follow pragmatic principles in order to maximize the information provided to stakeholders, will examine not only the effectiveness of each tested intervention but also provide meaningful information regarding effectiveness across key subgroups of patients. The knowledge gained will contribute to the development of translatable therapeutic strategies for the treatment of patients with KOA pain that will lead to opioid sparing effects.