Effects of NSAIDs and non-NSAID Analgesics on Osteoarthritis Outcomes

项目摘要/摘要 2008年，至少有2700万美国成年人患上了骨关节炎，预计这一数字将上升到约50 到2020年，由于日益增长的肥胖症和人口老龄化，全球人口将达到100万。是世界上导致残疾的主要原因， 根据Global的数据，骨关节炎导致残疾寿命(YLDs)增加了约30% 疾病负担2016年估计。然而，目前还没有针对骨性关节炎的确切治疗方法。全膝关节数 当医疗和康复努力失败时，替代治疗是骨关节炎的最终终点，预计将 到2030年，每年增加到350万。到目前为止，医疗干预主要集中在缓解疼痛的干预上， 非类固醇抗炎药(NSAIDs)和非NSAID镇痛剂是主要的非手术药物 治疗选择。尽管这些药物被广泛使用，但它们对人的潜在不利影响 疾病的长期特征不是很好。具体地说，关于如何减少慢性疼痛的数据有限 患有骨性关节炎的患者会影响疾病进展的风险或膝盖的风险 替补。该项目的长期目标是促进临床医生和患者的决策。 骨性关节炎慢性疼痛缓解干预的更优化治疗策略。的中心假说 这一建议是，与非类固醇抗炎药使用者相比，非非类固醇类止痛药使用者患长期-非类固醇抗炎药的风险增加。 长期骨关节炎的不良后果，包括疾病进展(通过X光确定)和膝关节 替补。虽然这两种止痛药在有效缓解疼痛的情况下可能会产生更高水平的伤害性 只有非类固醇抗炎药可以通过减少关节内炎症来减轻这种损害。非NSAID止痛药， 与非甾体抗炎药不同的是，它缺乏能够充分减少关节内炎症的抗炎特性 足以将潜在的损害降到最低。我们建议使用骨关节炎倡议(OAI)队列，一个 对有膝骨性关节炎或有膝骨性关节炎风险的人的纵向研究，每年研究一次，超过10年，有广泛的 临床、成像和用药数据。我们的目标是：描述骨关节炎的时变效应。 1)非NSAID纯止痛药的结果，2)处方NSAID的结果，以及3)比较非NSAID的效果 止痛药与非类固醇抗炎药的止痛药。这项工作的贡献很大，因为这两种类型的 治疗骨关节炎的药物是最广泛使用的药物之一。我们的新分析方法与 不允许使用药物的暴露的限制性定义的传统方法是 间歇性(即时变)或不允许治疗切换。与时间不变的方法不同， 对疼痛的变化无动于衷，我们的时变方法将使我们能够解释疼痛的时间依赖效应 疼痛，干预或治疗切换的主要指标。我们的工作将提供关于效应的新证据 关于疾病结果的广泛使用的药物，并将为治疗选择提供信息。

PROJECT SUMMARY/ABSTRACT Osteoarthritis affected at least 27 million US adults in 2008, and that number is expected to rise to about 50 million by 2020 because of growing obesity and the aging population. A leading cause of disability in the world, osteoarthritis has contributed to about 30% increase in Years Lived with Disability (YLDs) according to Global Burden of Disease 2016 estimates. Yet, no definitive treatment exists for osteoarthritis. The number of total knee replacements, the ultimate end-point of osteoarthritis when medical and rehabilitative efforts fail, is expected to rise to 3.5 million annually by 2030. Medical interventions so far have focused on pain-relieving interventions, with nonsteroidal anti-inflammatory drugs (NSAIDs) and non-NSAID analgesics being the primary non-surgical treatment choices. Despite the widespread use of these medications, their potential adverse effects on the disease in the long-term is not well characterized. Specifically, limited data exist on how reducing chronic pain in patients suffering from osteoarthritis would affect the risk of disease progression or the risk of knee replacement. The long-term goal of this project is to facilitate decision making for clinicians and patients of a more optimal treatment strategy for chronic pain relief interventions in osteoarthritis. The central hypothesis of this proposal is that non-NSAID analgesics users, compared to NSAIDs users, are at an increased risk of long- term osteoarthritis adverse outcomes, including disease progression (determined radiographically) and knee replacement. While both types of pain relievers may, with effective pain relief, produce higher levels of injurious activity, only NSAIDs may mitigate this damage by reducing intra-articular inflammation. Non-NSAID analgesics, unlike NSAIDs, lack anti-inflammatory properties that could reduce intra-articular inflammation sufficiently enough to minimize potential damage. We propose to use the Osteoarthritis Initiative (OAI) cohort, a longitudinal study of persons with or at risk of knee osteoarthritis studied annually over 10 years, with extensive clinical, imaging, and medication use data. Our aims are: to characterize the time-varying effects on osteoarthritis outcomes of 1) non-NSAID pure analgesics, 2) prescription NSAIDs, and 3) to compare the effects of non-NSAID analgesics with those from NSAIDs. The contribution of this work is significant because these two types of medications are among the most widely used for osteoarthritis. Our novel analytic approach is a departure from the traditional approaches of a restrictive definition of exposure that did not allow medication use to be intermittent (i.e. time-varying) or did not allow treatment switching. Unlike time-invariant approaches that were indifferent to changes in pain, our time-varying approach will allow us to account for time-dependent effect of pain, the main indicator for intervention or treatment switching. Our work will provide new evidence about effects of widely used medication of disease outcomes and will inform treatment choices.