Oral Adherence Trajectories Of Disease Modifying Agents And Associated Relapse Rates Among Patients With Multiple Sclerosis

多发性硬化症患者疾病调节剂的口服依从轨迹和相关复发率

基本信息

批准号：
10434699
负责人：
Rajender R Aparasu
金额：
$ 2.58万
依托单位：
UNIVERSITY OF HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10434699
关键词：
Oral Adherence Trajectories Disease Modifying

项目摘要

Adherence to Disease Modifying Agents (DMAs) is vital for disease management of Multiple Sclerosis (MS). The route of administration of DMA is one of the important factors associated with adherence in general and MS in specific. With the advent of oral DMAs in the last decade, the landscape of DMA treatment has changed significantly. Oral DMAs offer convenience in administration and offer other benefits over conventional injectable DMAs. Most of the previous studies assessed annual DMA adherence as a point estimate using medication possession ratio or proportion of days covered which failed to account for time-related changes in the adherence patterns over time. The Group-Based Trajectory Modeling (GBTM) classifies individuals into different adherence trajectory groups based on the prescription-filling pattern over time. Our preliminary analyses involving 2010- 2012 MarketScan revealed that oral fingolimod was associated with higher odds of being a complete adherer (Odds Ratio (OR): 2.78, 95% Confidence Interval (CI):1.85-4.16) or a slow discontinuer (OR: 2.62, 95% CI: 1.70- 1.05) relative to injectable DMA. In the past decade, several other new oral DMAs were introduced to treat MS, such as teriflunomide and dimethyl fumarate. These oral DMAs differ in their treatment regimen and may have consequences with respect to adherence and relapse. However, there is no real-world evidence regarding the adherence patterns over time and associated relapse rates with oral DMAs in MS. Therefore, the overall goal of this research is to evaluate adherence trajectories of oral DMAs over time and associated outcomes in MS patients. The specific aims of this study are: (1) to evaluate DMA adherence trajectory patterns of oral DMAs in MS; and (2) to evaluate the effect of adherence trajectories on relapse rates in MS. This study tests the following hypotheses- (i) adherence trajectory patterns differ across different oral DMAs, and (ii) patients with better adherence trajectories will have lower relapse rates. This retrospective observational study will involve adults with MS, with incident oral DMA use from the 2016-2018 MarketScan. The oral DMAs will involve three agents, namely, fingolimod, teriflunomide, and dimethyl fumarate. Relapse will be defined as inpatient hospitalization or an outpatient visit with a corticosteroid prescription within 30 days. The novel GBTM will involve finite mixture modeling for approximating adherence trajectories of oral DMA use over a one-year period. The study will adjust for selection bias within the multivariable context of the Andersen Behavioral Model. Multinomial regression using Inverse Probability Treatment Weights (IPTW) based on Generalized Boosted Models (GBM) will be used to evaluate trajectory patterns across different oral DMAs. Poisson regression models with IPTW based on GBM will be used to evaluate the relapse rates across oral DMAs with variable adherence trajectories. The study findings will provide valuable real-world evidence regarding adherence trajectories of oral DMAs and associated outcomes in MS. The study will have significant clinical and policy implications for understanding and improving medication adherence of oral DMAs to improve the quality of pharmaceutical care for MS patients.

坚持使用疾病修饰剂 (DMA) 对于多发性硬化症 (MS) 的疾病管理至关重要。这 DMA 的给药途径是与一般依从性和 MS 相关的重要因素之一具体的。随着过去十年口服 DMA 的出现，DMA 治疗的格局发生了变化显著地。与传统注射剂相比，口服 DMA 不仅给药方便，而且具有其他优点 DMA。之前的大多数研究将年度 DMA 依从性作为使用药物的点估计进行评估未能考虑到依从性中与时间相关的变化的占有率或覆盖天数比例随着时间的推移的模式。基于群体的轨迹建模（GBTM）将个体分为不同的依从性随着时间的推移，基于处方填充模式的轨迹分组。我们的初步分析涉及 2010- 2012 年 MarketScan 显示口服芬戈莫德与完全依从者的几率更高有关（优势比 (OR)：2.78，95% 置信区间 (CI)：1.85-4.16）或缓慢停药（OR：2.62，95% CI：1.70- 1.05) 相对于可注入 DMA。在过去的十年中，引入了其他几种新的口服 DMA 来治疗多发性硬化症，例如特立氟胺和富马酸二甲酯。这些口服 DMA 的治疗方案有所不同，并且可能具有关于坚持和复发的后果。然而，没有现实世界的证据表明随着时间的推移，MS 中口服 DMA 的依从模式以及相关的复发率。因此，总体目标是本研究旨在评估口服 DMA 随着时间的推移的依从轨迹以及 MS 的相关结果患者。本研究的具体目的是：（1）评估口服 DMA 的 DMA 依从轨迹模式多发性硬化症; (2) 评估坚持轨迹对 MS 复发率的影响。本研究测试了以下内容假设 - (i) 不同口服 DMA 的依从轨迹模式不同，以及 (ii) 具有更好的患者坚持轨迹将具有较低的复发率。这项回顾性观察研究将涉及成年人与 MS，以及 2016-2018 年 MarketScan 中事件口服 DMA 的使用。口服 DMA 将涉及三种药物，即芬戈莫德、特立氟胺和富马酸二甲酯。复发将被定义为住院或 30 天内使用皮质类固醇处方进行门诊就诊。新颖的 GBTM 将涉及有限混合用于近似一年内口服 DMA 使用依从轨迹的模型。研究会调整安徒生行为模型的多变量背景下的选择偏差。多项式回归使用基于广义增强模型 (GBM) 的逆概率处理权重 (IPTW) 将用于评估不同口腔 DMA 的轨迹模式。基于GBM的IPTW泊松回归模型将用于评估具有可变依从轨迹的口服 DMA 的复发率。研究研究结果将为有关口服 DMA 和相关药物的依从轨迹提供有价值的现实证据。 MS 的结果。该研究将对理解和改进具有重大的临床和政策意义。口服 DMA 的用药依从性，以提高多发性硬化症患者的药学护理质量。