The Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, Glostrup 2600, Denmark; Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, Glostrup 2600, Denmark.
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, Glostrup 2600, Denmark.
Mult Scler Relat Disord. 2020 May;40:101956. doi: 10.1016/j.msard.2020.101956. Epub 2020 Jan 17.
A consensus of early treatment with disease-modifying therapies (DMT) in multiple sclerosis (MS) has been reached based on several observational and experimental studies in adults. However, paediatric onset (PO)MS appears phenotypically different from adult onset MS, characterized by increased relapse rate and pronounced radiological activity on MRI. The objective of this study was to investigate the long-term consequences of delayed treatment start in POMS on disability in a real-world, population-based setting.
Based on prospectively collected data from The Danish Multiple Sclerosis Registry, we defined a cohort of MS patients with onset before the age of 18 years, who were born in 1980 or later, and started treatment with a DMT between 1998 and 2018. The POMS cohort was stratified according to treatment start within 2 years of onset (N = 140) or later (N = 151). Annualised relapse rate in each study group was compared using a negative binomial regression; and Cox proportional hazard model was used to estimate hazard ratios (HR) of time to sustained Expanded Disability Status Scale (EDSS) score 4, 6-month confirmed EDSS worsening and 6-month confirmed EDSS improvement, respectively, according to disease duration.
The POMS cohort had a total median follow-up time of 7.7 years (interquartile range 4.6-11.6). There was no association between risk of relapses in patients with delayed treatment start compared to earlier treatment start. Patients starting on a DMT later than 2 years after onset had a 2.52-fold increased risk of reaching sustained EDSS 4 compared to those starting within 2 years of onset (HR=2.52, 95% confidence interval (CI)=1.01-6.34). For every year increment from onset to start of first DMT, the risk of reaching sustained EDSS 4 increased by 17% (HR=1.17, 95% CI=1.05-1.30). In line with this, the risk of reaching confirmed EDSS worsening was increased by 44% compared to those starting earlier, although not statistically significant (HR=1.44, 95% CI=0.95-2.19). Starting on a DMT later was associated with 61% decreased chance of confirmed EDSS improvement compared to those starting earlier (HR=0.39, 95% CI=0.26-0.59). For every year increment from onset to starting DMT, the risk of confirmed EDSS improvement decreased by 10% (HR=0.90, 95% CI=0.84-0.96).
Delayed treatment start in this POMS cohort was associated with shorter time to reach sustained EDSS 4 and confirmed EDSS worsening, and decreased chance of reaching confirmed EDSS improvement, and thus support early treatment start in POMS patients.
多项成人多发性硬化症（MS）的观察性和实验性研究得出共识，即早期采用疾病修正疗法（DMT）治疗。然而，儿科发病（POMS）的表型与成人发病 MS 明显不同，其特点是复发率增加，磁共振成像（MRI）上的放射学活动明显。本研究旨在探讨在真实世界的人群中，POMS 患者延迟治疗开始对残疾的长期影响。
基于前瞻性收集的丹麦多发性硬化症登记处的数据，我们定义了一个发病年龄在 18 岁以下、出生于 1980 年或之后且在 1998 年至 2018 年期间开始使用 DMT 的 MS 患者队列。根据发病后 2 年内（N=140）或之后（N=151）开始治疗，将 POMS 队列分层。在每个研究组中，使用负二项回归比较每年复发率；并根据疾病持续时间，使用 Cox 比例风险模型估计达到持续扩展残疾状态量表（EDSS）评分 4、6 个月确认 EDSS 恶化和 6 个月确认 EDSS 改善的风险比（HR）。
POMS 队列的总中位随访时间为 7.7 年（四分位距 4.6-11.6）。与早期治疗相比，延迟治疗开始的患者发生复发的风险没有差异。与发病后 2 年内开始治疗的患者相比，发病后 2 年以上开始 DMT 治疗的患者达到持续 EDSS 4 的风险增加了 2.52 倍（HR=2.52，95%置信区间[CI]=1.01-6.34）。从发病到开始使用首次 DMT 的每增加 1 年，达到持续 EDSS 4 的风险增加 17%（HR=1.17，95%CI=1.05-1.30）。与此一致的是，与较早开始治疗的患者相比，达到确认 EDSS 恶化的风险增加了 44%，尽管没有统计学意义（HR=1.44，95%CI=0.95-2.19）。与较早开始治疗相比，较晚开始 DMT 治疗与确认 EDSS 改善的几率降低 61%相关（HR=0.39，95%CI=0.26-0.59）。从发病到开始 DMT 的每增加 1 年，确认 EDSS 改善的风险降低 10%（HR=0.90，95%CI=0.84-0.96）。
在这个 POMS 队列中，延迟治疗开始与更快达到持续 EDSS 4 和确认 EDSS 恶化，以及改善确认 EDSS 的几率降低有关，因此支持在 POMS 患者中早期治疗。
