Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.
J Neurol. 2022 Oct;269(10):5382-5394. doi: 10.1007/s00415-022-11193-w. Epub 2022 May 24.
Multiple sclerosis (MS) is a chronic and progressive neurological disease that is characterized by neuroinflammation, demyelination and neurodegeneration occurring from the earliest phases of the disease and that may be underestimated. MS patients accumulate disability through relapse-associated worsening or progression independent of relapse activity. Early intervention with high-efficacy disease-modifying therapies (HE-DMTs) may represent the best window of opportunity to delay irreversible central nervous system damage and MS-related disability progression by hindering underlying heterogeneous pathophysiological processes contributing to disability progression. In line with this, growing evidence suggests that early use of HE-DMTs is associated with a significant greater reduction not only of inflammatory activity (clinical relapses and new lesion formation at magnetic resonance imaging) but also of disease progression, in terms of accumulation of irreversible clinical disability and neurodegeneration compared to delayed HE-DMT use or escalation strategy. These beneficial effects seem to be associated with acceptable long-term safety risks, thus configuring this treatment approach as that with the most positive benefit/risk profile. Accordingly, it should be mandatory to treat people with MS early with HE-DMTs in case of prognostic factors suggestive of aggressive disease, and it may be advisable to offer an HE-DMT to MS patients early after diagnosis, taking into account drug safety profile, disease severity, clinical and/or radiological activity, and patient-related factors, including possible comorbidities, family planning, and patients' preference in agreement with the EAN/ECTRIMS and AAN guidelines. Barriers for an early use of HE-DMTs include concerns for long-term safety, challenges in the management of treatment initiation and monitoring, negative MS patients' preferences, restricted access to HE-DMTs according to guidelines and regulatory rules, and sustainability. However, these barriers do not apply to each HE-DMT and none of these appear insuperable.
多发性硬化症（MS）是一种慢性进行性神经系统疾病，其特征是神经炎症、脱髓鞘和神经退行性变发生在疾病的最早阶段，且可能被低估。MS 患者通过与复发相关的恶化或独立于复发活动的进展而累积残疾。通过阻碍导致残疾进展的潜在异质病理生理过程，早期使用高效疾病修正治疗（HE-DMT）可能代表延迟不可逆转的中枢神经系统损伤和 MS 相关残疾进展的最佳机会窗口。基于这一点，越来越多的证据表明，与延迟使用 HE-DMT 或升级策略相比，早期使用 HE-DMT 不仅可以显著降低炎症活动（磁共振成像上的临床复发和新病变形成），而且可以显著降低疾病进展，包括累积不可逆的临床残疾和神经退行性变。这些有益的效果似乎与可接受的长期安全性风险相关，因此这种治疗方法具有最积极的获益/风险特征。因此，在存在提示疾病进展的预后因素的情况下，应强制性地早期用 HE-DMT 治疗 MS 患者，并且可能需要在考虑药物安全性特征、疾病严重程度、临床和/或放射学活动以及患者相关因素（包括可能的合并症、生育计划和患者偏好）的情况下，在诊断后早期为 MS 患者提供 HE-DMT，这些因素包括可能的合并症、生育计划和患者偏好，这些因素与 EAN/ECTRIMS 和 AAN 指南一致。早期使用 HE-DMT 的障碍包括对长期安全性的担忧、治疗开始和监测管理方面的挑战、MS 患者的负面偏好、根据指南和监管规则对 HE-DMT 的限制以及可持续性。然而，这些障碍并不适用于每种 HE-DMT，而且这些障碍都不是不可逾越的。
