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.

项目概要/摘要 疾病修饰剂 (DMA) 对于减少多种炎症和限制疾病活动至关重要 硬化症（MS）。然而，由于以下原因，患有多发性硬化症的老年人的炎症和疾病活动度有所下降： 疾病的自然进展。事实上，大多数 65 岁以上的多发性硬化症患者的疾病活动度非常有限，并且 复发。 DMA 不能有效预防与衰老相关的残疾和疾病进展。那里 关于 DMA 对患有 MS 的老年人的有效性的数据也非常有限。此外，DMA 的使用还与 感染、恶性肿瘤和其他不良事件增加。老年人持续使用 DMA 备受争议 由于尚未证实疗效、安全性问题和高昂的处方成本。因此，迫切需要 评估老年人停用 DMA 的益处和安全性。尽管一些研究有限 样本发现 DMA 停用的初步证据，未进行大规模药物流行病学研究 评估了老年人停用 DMA 的安全性和有效性。我们之前的基础研究 发现患有多发性硬化症的老年人接受注射剂（55%），其次是口服剂（32%）。然而，超过 35% 的老年人 成人在 12 个月后停止使用 DMA。本研究的总体目标是评估停用处方 以及老年多发性硬化症患者的相关有效性和安全性结果。具体目标 研究目的是：(1) 检查 DMA 在老年多发性硬化症患者中的使用和停用情况； (2)评估DMA的效果 降低复发率和虚弱程度； (3) 评估 DMA 停用对严重感染的效果 以及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纵向队列 根据涉及 A、B 部分的 10 年 Medicare 索赔数据，年龄超过 65 岁且使用 MS 和 DMA D. 该研究将检验以下假设：(i) 患有以下疾病的老年人的复发率和虚弱程度没有差异： 被取消处方，并且继续 DMA 的患者，(ii) 取消 DMA 与减少相关 患有多发性硬化症的老年人的感染率和全因死亡率。取消处方将被定义为 停止 DMA 至少 12 个月，并以一年为基准坚持 DMA（天数比例） 覆盖>0.80）。比较组将是那些继续进行 DMA 的人。复发率和虚弱将 使用经过验证的基于声明的算法进行操作。严重感染和特定类型的风险 感染和死亡率也将得到评估。该研究将涉及倾向得分匹配的队列 基于广义增强模型的设计，以调整多元背景下的选择偏差 安徒生行为模型。倾向得分匹配集中的多变量模型将用于 评估有效性和安全性结果。涉及不同分析的多重敏感性分析 将进行考虑以评估调查结果的稳健性。这将是第一个全国性研究 提供有关 DMA 停用和相关结果的有价值的现实证据 对改善老年多发性硬化症患者的处方实践和护理质量的临床和政策影响。