Marriott James John, Ekuma Okechukwu, Fransoo Randall, Marrie Ruth Ann
Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
Manitoba Centre for Health Policy, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Front Neurol. 2023 Sep 6;14:1243589. doi: 10.3389/fneur.2023.1243589. eCollection 2023.
While randomized, controlled trials (RCTs) are the gold standard for determining treatment efficacy, they do not capture the effectiveness of treatment during real-world use. We aimed to evaluate the association between demographics and multiple sclerosis (MS) disease-modifying therapy (DMT) exposure, including treatment adherence and switches between different DMTs, on the risk of subsequent MS relapse.
All persons with relapsing-onset MS (pwRMS) living in Manitoba between 1999 and 2014 were identified from provincial healthcare databases using a validated case definition. Use of DMTs was abstracted from the provincial drug database covering all residents of Manitoba, including use of any DMT, stopping/starting any DMT, switches between different DMTs and adherence as defined by cumulative medication possession ratios (CUMMPRs) of 50, 70, 80 and 90%. Time to first-treated relapse was used as the outcome of interest in logistic regression and Cox-proportional hazards regression models adjusting for demographic covariates including age and year of diagnosis, sex, socioeconomic status and number of medical comorbidities.
1780 pwRMS were identified, including 1,510 who were on DMT at some point in the study period. While total DMT exposure was not associated with the time to subsequent treated relapse, individuals who switched between more than 2 DMTs had higher post-switch rates of relapse. Switching to second-line DMTs was associated with a longer time to treated relapse in comparison to those who remained on a first-line DMT (HR 0.44; 95%CI: 0.32-0.62, < 0.0001).
Switching to high-efficacy DMTs reduces the rates of subsequent MS relapse at the population level.
虽然随机对照试验（RCT）是确定治疗效果的金标准，但它们无法反映实际应用中治疗的有效性。我们旨在评估人口统计学因素与多发性硬化症（MS）疾病修饰治疗（DMT）暴露之间的关联，包括治疗依从性以及不同DMT之间的转换，对后续MS复发风险的影响。
利用经过验证的病例定义，从省级医疗数据库中识别出1999年至2014年居住在曼尼托巴省的所有复发型MS患者（pwRMS）。从涵盖曼尼托巴省所有居民的省级药物数据库中提取DMT的使用情况，包括任何DMT的使用、停止/开始使用任何DMT、不同DMT之间的转换以及按照累积药物持有率（CUMMPR）为50%、70%、80%和90%定义的依从性。首次治疗复发时间用作逻辑回归和Cox比例风险回归模型中的感兴趣结局，对包括年龄、诊断年份、性别、社会经济地位和医疗合并症数量在内的人口统计学协变量进行调整。
共识别出1780例pwRMS，其中1510例在研究期间的某个时间点接受了DMT治疗。虽然总的DMT暴露与后续治疗复发时间无关，但在超过2种DMT之间转换的个体在转换后的复发率更高。与继续使用一线DMT的患者相比，转换至二线DMT与更长的治疗复发时间相关（风险比0.44；95%置信区间：0. .32 - 0.62，P < 0.0001）。
在人群层面，转换至高疗效DMT可降低后续MS复发率。
