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坚持疾病修正治疗对多发性硬化症长期临床和经济结局的影响:基于真实世界数据的索赔分析

Impact of adherence to disease modifying therapies on long-term clinical and economic outcomes in multiple sclerosis: A claims analysis of real-world data.

作者信息

Amezcua Lilyana, Livingston Terrie, Hayward Brooke, Zhou Jia, Williams Mitzi J

机构信息

Department of Neurology, Keck School of Medicine, University of Southern California, USA.

One Technology Place, EMD Serono, Inc., Rockland, MA, USA.

出版信息

Mult Scler Relat Disord. 2023 Sep;77:104866. doi: 10.1016/j.msard.2023.104866. Epub 2023 Jul 1.

Abstract

BACKGROUND

Multiple sclerosis (MS) is a chronic neurodegenerative inflammatory disease that requires long-term commitment to treatment for optimal outcomes. A variety of disease-modifying therapies (DMTs) are now available that reduce relapses and delay disease progression in people with MS. However, adherence remains a significant issue, with a variety of mental, physical, and emotional factors contributing to non-adherence. In a large number of studies, non-adherence has been associated with worse clinical outcomes (relapses and disease severity), a higher economic burden, and loss of work productivity. However, many of these studies were short-term (1-2 years) or cross-sectional studies; thus, more data are needed on the long-term clinical and economic impacts of DMT non-adherence. The objective of this study was to determine the longer-term impact of adherence to DMTs on disease activity and healthcare resource utilization (HCRU) in people with MS. The study hypothesis was that non-adherence to DMTs would be associated long-term with worse clinical outcomes and a higher economic burden.

METHODS

A retrospective administrative claims analysis of the US MarketScan® Commercial database (2011-2017) in individuals (18-65 years) with MS (based on International Classification of Disease coding) was conducted. Adherence was classified by proportion of days covered (PDC) ≥0.8 and non-adherence by PDC <0.8; sensitivity analyses helped further categorize as moderately (PDC ≥0.6-<0.8) or highly (PDC <0.6) non-adherent. Cohorts were matched using propensity score matching. Time to first relapse, annualized relapse rate (ARR), time to use of assistive devices (cane/walker or wheelchair), and annual HCRU (inpatient, emergency room [ER], outpatient, and MRI visits and costs) were compared between cohorts.

RESULTS

10,248 MS cases were identified; 58% met adherence criteria, and 42% met non-adherence criteria. Mean follow-up from diagnosis or first DMT claim was 5.3 years. Adherent individuals had a longer time to first relapse (hazard ratio [HR] 0.83; 95% confidence interval [CI]: 0.77-0.90; p<0.0001), a lower ARR (0.13 vs. 0.18, respectively; rate ratio [RR] 0.75 [95% CI: 0.71-0.79]; p<0.0001), and longer lag times to cane/walker use (HR 0.79 [95% CI: 0.66-0.94]; p=0.0067) and wheelchair use (HR 0.68 [95% CI: 0.55-0.83]; p=0.0002) than non-adherent individuals. Adherent individuals had fewer annual inpatient and ER visits and lower total costs than those who were non-adherent (p<0.0001). Sensitivity analyses showed that differences in disease activity and HCRU were generally more pronounced between matched adherent and highly non-adherent pairs than between matched adherent and moderately non-adherent pairs.

CONCLUSION

Significant differences in MS disease activity and HCRU were observed based on adherence to DMTs. Our study underscores the negative impact of non-adherence to DMTs on long-term clinical and economic outcomes in MS.

摘要

背景

多发性硬化症(MS)是一种慢性神经退行性炎症性疾病,需要长期坚持治疗以获得最佳疗效。目前有多种疾病修正疗法(DMTs)可用于减少MS患者的复发并延缓疾病进展。然而,治疗依从性仍然是一个重要问题,多种心理、身体和情感因素导致患者不依从治疗。在大量研究中,不依从治疗与更差的临床结局(复发和疾病严重程度)、更高的经济负担以及工作生产力损失相关。然而,这些研究大多是短期(1 - 2年)或横断面研究;因此,需要更多关于DMT不依从治疗的长期临床和经济影响的数据。本研究的目的是确定坚持使用DMTs对MS患者疾病活动和医疗资源利用(HCRU)的长期影响。研究假设是,长期不依从DMTs将与更差的临床结局和更高的经济负担相关。

方法

对美国MarketScan®商业数据库(2011 - 2017年)中年龄在18 - 65岁、患有MS(基于国际疾病分类编码)的个体进行回顾性管理索赔分析。依从性通过覆盖天数比例(PDC)≥0.8进行分类,不依从性通过PDC < 0.8进行分类;敏感性分析有助于进一步分为中度(PDC≥0.6 - < 0.8)或高度(PDC < 0.6)不依从。使用倾向得分匹配对队列进行匹配。比较队列之间首次复发时间、年化复发率(ARR)、使用辅助设备(手杖/助行器或轮椅)的时间以及年度HCRU(住院、急诊室[ER]、门诊和MRI就诊及费用)。

结果

共识别出10248例MS病例;58%符合依从标准,42%符合不依从标准。从诊断或首次DMT索赔开始的平均随访时间为5.3年。依从治疗的个体首次复发时间更长(风险比[HR] 0.83;95%置信区间[CI]:0.77 - 0.90;p < 0.0001),ARR更低(分别为0.13和0.18;率比[RR] 0.75 [95% CI:0.71 - 0.79];p < 0.0001),使用手杖/助行器和轮椅的延迟时间也比不依从治疗的个体更长(使用手杖/助行器的HR为0.79 [95% CI:0.66 - 0.94];p = 0.0067;使用轮椅的HR为0.68 [95% CI:0.55 - 0.83];p = 0.0002)。依从治疗的个体每年的住院和急诊就诊次数更少,总成本也低于不依从治疗的个体(p < 0.0001)。敏感性分析表明,在匹配的依从和高度不依从组对之间,疾病活动和HCRU的差异通常比匹配的依从和中度不依从组对之间更为明显。

结论

基于对DMTs的依从性,观察到MS疾病活动和HCRU存在显著差异。我们的研究强调了不依从DMTs对MS长期临床和经济结局的负面影响。

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