Effects of NSAIDs and non-NSAID Analgesics on Osteoarthritis Outcomes

NSAID 和非 NSAID 镇痛药对骨关节炎结局的影响

• 批准号: 9584172
• 负责人: S. Reza Jafarzadeh
• 金额: $ 8.25万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9584172
• 关键词: Accounting; Address; Adherence; Adult; Adverse effects; Affect; American; Analgesics; Anti-inflammatory; Arthritis; Body mass index; Cessation of life; Clinical; Complex; Data; Decision Making; Degenerative polyarthritis; Deterioration; Diagnostic radiologic examination; Disease; Disease Outcome; Disease Progression; Drug usage; Drug user; GTP-Binding Protein alpha Subunits, Gs; Goals; Growth Inhibitors; Hip region structure; Image; Indomethacin; Inflammation; Injury; Intervention; Joints; Knee; Knee Osteoarthritis; Knowledge; Lead; Long-Term Effects; Longitudinal Studies; Medical; Methods; Modeling; Modernization; Nerve; Non-Steroidal Anti-Inflammatory Agents; Obesity; Observational Study; Outcome; Pain; Patient-Focused Outcomes; Patients; Persons; Pharmaceutical Preparations; Property; Rehabilitation therapy; Replacement Arthroplasty; Research Methodology; Rheumatism; Risk; Time; Work; adverse outcome; aging population; burden of illness; chronic pain; chronic pain relief; cohort; design; disability; disorder risk; epidemiology study; experience; follow-up; high risk; improved functioning; insight; knee pain; knee replacement arthroplasty; novel; optimal treatments; pain reduction; pain relief; randomized trial; study population; temporal measurement; treatment choice; treatment strategy; years lived with disability

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.

项目总结/摘要 2008年，美国至少有2700万成年人患有骨关节炎，预计这一数字将上升到50 到2020年，由于肥胖和人口老龄化的增加，这是世界上导致残疾的主要原因， 据全球统计，骨关节炎导致残疾生活年数（YLD）增加约30%。 疾病负担2016年估计。然而，对于骨关节炎还没有确定的治疗方法。全膝关节数 当医疗和康复努力失败时，关节置换是骨关节炎的最终终点， 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， 非甾体类抗炎药（NSAID）和非NSAID镇痛药是主要的非手术 治疗选择。尽管这些药物被广泛使用，但它们对患者的潜在不良影响仍然存在。 长期的疾病没有得到很好的描述。具体来说，关于如何减少慢性疼痛的数据有限。 在患有骨关节炎的患者中， 更换.该项目的长期目标是促进临床医生和患者的决策， 骨关节炎慢性疼痛缓解干预的最佳治疗策略。的中心假设 这一建议是，与NSAID使用者相比，非NSAID镇痛剂使用者的长期- 长期骨关节炎不良结局，包括疾病进展（通过放射学确定）和膝关节 更换.虽然这两种类型的止痛药都可以有效缓解疼痛，但会产生更高水平的伤害性疼痛。 活动，只有NSAID可以减轻这种损害，减少关节内炎症。非NSAID镇痛药， 不像非甾体抗炎药，缺乏抗炎特性，可以充分减少关节内炎症 以尽量减少潜在的伤害。我们建议使用骨关节炎倡议（OAI）队列， 对膝关节骨关节炎患者或有膝关节骨关节炎风险的患者进行了为期10年的纵向研究， 临床、成像和药物使用数据。我们的目的是：描述骨关节炎的时变效应 1）非NSAID纯镇痛药，2）处方NSAID，和3）比较非NSAID的效果的结局 与NSAIDs的镇痛药。这项工作的贡献是显着的，因为这两种类型的 药物是最广泛用于骨关节炎的药物之一。我们新颖的分析方法是一种背离 传统的暴露的限制性定义方法不允许药物的使用， 间歇性（即时变）或不允许治疗切换。不像时不变的方法， 尽管我们对疼痛的变化漠不关心，但我们的时变方法将使我们能够解释 疼痛是干预或治疗转换的主要指标。我们的工作将提供有关影响的新证据 广泛使用的药物的疾病结果，并将告知治疗选择。