Deprescribing of Disease Modifying Agents in Older Adults with Multiple Sclerosis

患有多发性硬化症的老年人中取消疾病调节剂的处方

• 批准号: 10718559
• 负责人: Rajender R Aparasu
• 金额: $ 40万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10718559
• 关键词: Deprescribing; Disease; Modifying; Agents; Older

PROJECT SUMMARY/ABSTRACT Disease Modifying Agents (DMAs) are vital for reducing inflammation and limiting disease activity in multiple sclerosis (MS). However, there is a decline in inflammation and disease activity in older adults with MS due to natural disease progression. In fact, most patients with MS over age 65 have very limited disease activity and relapses. DMAs are not effective in preventing disability and disease progression associated with aging. There is also very limited data on the effectiveness of DMAs in older adults with MS. Also, DMA use is associated with increased infections, malignancy, and other adverse events. Continued DMA use in older adults is highly debated due to no proven efficacy, safety concerns, and high prescription costs. Therefore, there is an urgent need to evaluate the benefits and safety of DMA discontinuation in older adults. Although some studies with limited samples found preliminary evidence for DMA discontinuation, no large-scale pharmacoepidemiological study evaluated both the safety and effectiveness of DMA deprescribing in older adults. Our previous based study found that older adults with MS received injectables (55%), followed by orals (32%). However, over 35% of older adults discontinued their DMAs after 12 months. The overall goal of this research is to evaluate deprescribing and associated effectiveness and safety outcomes in older adults with MS. The specific objectives of the research are to: (1) examine DMA use and deprescribing in older adults with MS; (2) evaluate the effect of DMA deprescribing on relapse rates and frailty; and (3) evaluate the effect of DMA deprescribing on serious infections and all-cause mortality in older adults with MS. This study will involve a longitudinal national cohort of older adults over 65 years of age with MS and DMA use based on ten-year Medicare claims data involving Parts A, B, and D. The study will test the hypotheses that (i) there is no difference in relapse rates and frailty in older adults who are deprescribed and those who continue DMA, (ii) and DMA deprescribing is associated with decreased infection rates and all-cause mortality in older adults with MS. Deprescribing will be defined as the discontinuation of DMAs for at least 12 months with a one-year baseline adherence of DMAs (proportion of days covered of >0.80). The comparator group will be those continuing their DMAs. The relapse rates and frailty will be operationalized using validated claims-based algorithms. The risk of serious infections and specific types of infection, along with mortality, will also be evaluated. The study will involve a propensity score-matched cohort design based on generalized boosted models to adjust for the selection bias within the multivariate context of the Andersen Behavioral Model. Multivariable models within propensity score-matched sets will be used to evaluate the effectiveness and safety outcomes. Multiple sensitivity analyses involving differing analytical considerations will be conducted to assess the robustness of the findings. This will be the first national study to provide valuable real-world evidence regarding DMA deprescribing and associated outcomes with significant clinical and policy implications for improving prescribing practices and quality of care in older adults with MS.

项目摘要/摘要 疾病修饰剂(DMAS)对于减少炎症和限制疾病活动性至关重要 硬化症(MS)。然而，患有多发性硬化症的老年患者的炎症和疾病活动性有所下降，这是由于 自然疾病的发展。事实上，大多数65岁以上的多发性硬化症患者的疾病活动非常有限， 旧病复发。DMAS在预防残疾和与衰老相关的疾病进展方面并不有效。那里 在患有多发性硬化症的老年人中使用DMA的有效性的数据也非常有限。 感染、恶性肿瘤和其他不良事件的增加。老年人是否继续使用DMA引起了激烈的争论 由于没有证实的有效性，安全性问题，以及高昂的处方成本。因此，迫切需要 评估在老年人中停用DMA的益处和安全性。尽管一些研究有限 样本发现了停用DMA的初步证据，未进行大规模药物流行病学研究 评估了在老年人中停药的安全性和有效性。我们之前的基础研究 研究发现，患有多发性硬化症的老年人接受注射(55%)，其次是口服(32%)。然而，超过35%的老年人 成年人在12个月后停止服用DMA。这项研究的总体目标是评估停药 以及与MS有关的老年人的有效性和安全性结果 研究的目的是：(1)检查患有多发性硬化症的老年人的DMA使用和停药情况；(2)评估DMA的效果 停药对复发率和脆弱性的影响；以及(3)评估停药对严重感染的影响 患有多发性硬化症的老年人的全因死亡率这项研究将涉及全国老年人的纵向队列 65岁以上，使用MS和DMA，基于涉及A、B和 D.这项研究将检验以下假设：(I)在老年人中，复发率和脆弱程度没有差异 停药和继续服用DMA的人，(Ii)和停用DMA与减少 停药的老年人的感染率和全因死亡率将被定义为 中断DMAS至少12个月，并在一年内遵守DMAS(天数比例 覆盖了&gt；0.80)。比较组将是那些继续他们的DMA的人。复发率和脆弱的意志 使用经过验证的基于索赔的算法进行操作。严重感染的风险和特定类型的 感染以及死亡率也将进行评估。这项研究将包括一组倾向得分匹配的队列 基于广义Boost模型的设计，以调整在多变量背景下的选择偏差 安徒生行为模式。倾向得分匹配集合中的多变量模型将用于 评估有效性和安全性结果。涉及不同分析方法的多重敏感性分析 将对调查结果的稳健性进行评估。这将是第一项全国性的研究 提供有关DMA停药的有价值的真实世界证据和相关结果 改善老年MS患者的处方实践和护理质量的临床和政策影响