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Cumulative effects of therapies on disability in relapsing multiple sclerosis
Multiple Sclerosis Journal ( IF 5.8 ) Pub Date : 2021-01-06 , DOI: 10.1177/1352458520980366
Fabien Rollot 1 , Romain Casey 1 , Emmanuelle Leray 2 , Marc Debouverie 3 , Gilles Edan 4 , Sandrine Wiertlewski 5 , Sandra Vukusic 1 , David-Axel Laplaud 6
Affiliation  

BACKGROUND Long-term effectiveness of treatment remains a key question in multiple sclerosis (MS) and the cumulative effects of past treatment have not been investigated so far. OBJECTIVE Explore the relationship between treatment exposure and disability risk in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS A total of 2285 adult patients from the French nationwide cohort were included. Outcomes were irreversible EDSS4, and conversion to secondary progression of multiple sclerosis (SPMS). Associations between treatments and risk of disability were assessed using a novel weighted cumulative exposure model, assuming a 3-year lag to account for reverse causality. This flexible approach accounts for past exposure in a multivariate Cox proportional hazards model by computing a weight function. RESULTS At baseline, mean ± standard deviation age of patients was 33.4 ± 8.9 years and 75.0% were women. A 15-year continuous treatment starting 20 years ago was associated with a decrease in risk of 26% for irreversible EDSS4, and 34% for SPMS compared to a 5-year treatment starting 10 years ago. The risk of disability decreased with increasing duration of exposure to disease-modifying treatment (DMT). CONCLUSION Long-term use of treatments in RRMS has a stronger beneficial cumulative impact than only early uses and delays the occurrence of moderate disability and conversion to SPMS.

中文翻译:

治疗对复发性多发性硬化症残疾的累积影响

背景治疗的长期有效性仍然是多发性硬化症 (MS) 的一个关键问题,迄今为止尚未研究过去治疗的累积效应。目的 探讨复发缓解型多发性硬化症 (RRMS) 患者的治疗暴露与残疾风险之间的关系。方法共纳入了来自法国全国队列的 2285 名成年患者。结果是不可逆的 EDSS4,并转化为多发性硬化症 (SPMS) 的继发性进展。使用新的加权累积暴露模型评估治疗与残疾风险之间的关联,假设滞后 3 年以解释反向因果关系。这种灵活的方法通过计算权重函数来解释多元 Cox 比例风险模型中的过去暴露。结果 在基线时,患者的平均 ± 标准差年龄为 33.4 ± 8.9 岁,75.0% 为女性。与 10 年前开始的 5 年治疗相比,20 年前开始的 15 年连续治疗与不可逆 EDSS4 的风险降低 26% 和 SPMS 的风险降低 34%。随着疾病缓解治疗 (DMT) 暴露时间的延长,残疾风险降低。结论 在 RRMS 中长期使用治疗比仅早期使用具有更强的有益累积影响,并延迟了中度残疾的发生和向 SPMS 的转变。残疾风险随着疾病缓解治疗 (DMT) 暴露时间的延长而降低。结论 在 RRMS 中长期使用治疗比仅早期使用具有更强的有益累积影响,并延迟了中度残疾的发生和向 SPMS 的转变。残疾风险随着疾病缓解治疗 (DMT) 暴露时间的延长而降低。结论 在 RRMS 中长期使用治疗比仅早期使用具有更强的有益累积影响,并延迟了中度残疾的发生和向 SPMS 的转变。
更新日期:2021-01-06
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