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

• 批准号: 10287874
• 负责人: Rajender R Aparasu
• 金额: $ 7.42万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10287874
• 关键词: Oral; Adherence; Trajectories; Disease; Modifying

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（DMAs）对于多发性硬化症（MS）的疾病管理至关重要。的 DMA的给药途径是一般情况下与依从性相关的重要因素之一， 特定.随着过去十年中口服DMA的出现，DMA治疗的前景发生了变化 显著口服DMAs给药方便，并提供其他优于常规注射剂的益处 DMA。以前的大多数研究评估了每年DMA的依从性，作为使用药物的点估计值 占有率或覆盖天数的比例，未能说明遵守时间的相关变化 随时间变化的模式。基于群体的轨迹建模（GBTM）将个体划分为不同的依从性 基于随时间的处方填充模式的轨迹组。我们对2010年的初步分析- 2012年市场扫描显示，口服芬戈莫德与成为完全依从者的几率较高相关 (Odds比值（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- 4.16） 1.05）相对于注射DMA。在过去的十年中，引入了其他几种新的口服DMA来治疗MS， 例如特立氟胺和富马酸二甲酯。这些口服DMA的治疗方案不同， 关于依从性和复发的后果。然而，没有现实世界的证据表明， MS患者口服DMA随时间的依从性模式和相关复发率。因此， 本研究旨在评估MS患者口服DMAs随时间推移的依从性轨迹和相关结局 患者本研究的具体目的是：（1）评估口服DMA的DMA依从性轨迹模式， MS;（2）评估依从性轨迹对MS复发率的影响。 假设-（i）不同口服DMA的依从性轨迹模式不同，以及（ii） 依从性轨迹将具有较低的复发率。这项回顾性观察性研究将涉及成年人 MS，2016-2018年MarketScan中的口服DMA事件。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。复发定义为住院治疗或 30天内接受过皮质类固醇处方的门诊访视。新的GBTM将涉及有限混合 模拟一年内口服DMA使用的近似依从性轨迹。这项研究将调整 选择偏差在多变量背景下的安德森行为模型。多项式回归使用 将使用基于广义提升模型（GBM）的逆概率治疗权重（IPTW）， 评估不同口腔DMA的轨迹模式。基于GBM的IPTW Poisson回归模型 将用于评价具有不同依从性轨迹的口服DMA的复发率。研究 研究结果将提供有价值的真实世界的证据，关于口服DMA的依从性轨迹和相关的 该研究将对理解和改善MS的临床和政策产生重大影响。 口服DMAs的药物依从性，以提高MS患者的药学服务质量。