CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia/Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
Rennes University, EHESP, REPERES - EA 7449, Rennes, France/Rennes University, CHU Rennes, Inserm, CIC 1414 [(Centre d'Investigation Clinique de Rennes)], Rennes, France.
Mult Scler. 2021 Oct;27(12):1838-1851. doi: 10.1177/1352458520981300. Epub 2021 Jan 11.
A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups.
The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation.
Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants.
High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5).
Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.
治疗效果的延迟出现，称为治疗滞后，可能会影响某些亚组患者对治疗反应的评估。
本研究旨在探讨患者和疾病特征与复发和残疾累积的治疗滞后的关系。
使用来自多国多发性硬化症（MS）登记处 MSBase 和法国 MS 登记处 OFSEP 的数据。纳入分析的患者诊断为 MS，至少有 1 年的 MS 治疗暴露和 3 年的治疗前随访。研究结果为复发和残疾累积的发生率。在按患者和疾病特征分层的亚组中，使用客观、经过验证的方法计算治疗滞后。然后，根据临床和人口统计学决定因素的组合，在亚组中估计特定情况下的治疗滞后。
基线残疾评分高、年复发率（ARR）≥1 和男性与残疾进展的治疗滞后较长相关：EDSS<6 和 ARR<1 的女性平均滞后时间为 26.6 周（95%CI=18.2-34.9），EDSS<6 和 ARR<1 的男性为 31.0 周（95%CI=25.3-36.8），EDSS<6 和 ARR≥1 的女性为 44.8 周（95%CI=24.5-65.1），EDSS≥6 和 ARR<1 的女性为 54.3 周（95%CI=47.2-61.5）。
治疗前 EDSS 和 ARR 是治疗滞后的最重要决定因素。
