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

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。这个 DMA的给药途径是影响MS患者依从性的重要因素之一 具体的。在过去的十年中，随着口服DMA的出现，DMA治疗的格局已经改变 意义重大。与传统的注射剂相比，口服DMA提供了方便的给药方法，并提供了其他好处 DMA。以前的大多数研究使用药物评估每年的DMA依从性作为一个点估计 持有率或覆盖天数的比例未能考虑与时间相关的依从性变化 随着时间的推移而形成的模式。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，基于处方配药模式的轨迹分组。我们对2010年的初步分析- 2012年MarketScan显示，口腔指模与完全粘连的几率更高相关 (优势比(OR)：2.78，95%可信区间(CI)：1.85-4.16)或缓慢断续者(OR：2.62，95%CI：1.70- 1.05)相对于可注射的DMA。在过去的十年里，其他几种新的口服DMA被引入治疗多发性硬化症， 如特氟米特和富马酸二甲酯。这些口服DMAS的治疗方案不同，可能有 坚持和故态复萌的后果。然而，没有真实世界的证据表明 MS患者随时间的依从性模式和与口服DMA相关的复发率因此，总的目标是 这项研究旨在评估口服DMAS随时间的依从性轨迹以及MS患者的相关结局 病人。本研究的具体目的是：(1)评价口腔中DMA的黏附轨迹模式 MS；和(2)评估依从性轨迹对MS复发率的影响。 假设-(I)不同口服DMA的粘连轨迹模式不同，以及(Ii)患者 依从性轨迹将具有较低的复发率。这项回溯性的观察性研究将涉及成年人 对于MS，2016-2018年的MarketScan中出现了口头DMA使用。口头DMAS将涉及三名特工， 即Fingolimod、Teriflunomide和富马酸二甲酯。复发将被定义为住院或 在30天内使用皮质类固醇处方进行门诊。新的GBTM将涉及有限混合 模拟一年内口服DMA使用的依从性轨迹。这项研究将进行调整 在安徒生行为模型的多变量背景下的选择偏差。使用多项式回归 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的带IPTW的Poisson回归模型 将用于评估具有可变依从性轨迹的口服DMA的复发率。这项研究 研究结果将提供有价值的真实世界证据，说明口服DMA和相关药物的依从性 多发性硬化症的结果这项研究将对理解和改进具有重要的临床和政策意义 提高多发性硬化症患者用药依从性的研究

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.