Department of Neurology, Danish Multiple Sclerosis Center, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark.
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, Ohio, USA.
Curr Opin Neurol. 2020 Jun;33(3):262-270. doi: 10.1097/WCO.0000000000000811.
Based on the knowledge of disease mechanisms in the progressive course of multiple sclerosis and the experience from randomized clinical trials, we assessed the timing of disease-modifying therapy in patients with progressive multiple sclerosis to define the optimal window of opportunity for treatment of progressive multiple sclerosis.
In progressive multiple sclerosis both small molecules that cross the blood--brain barrier (siponimod) and monoclonal antibodies (ocrelizumab) have shown therapeutic efficacy and have been approved for treatment of progressive multiple sclerosis. However, the majority of phase II and phase III trials in progressive forms of multiple sclerosis have been negative, probably owing to either late start of treatment or use of drugs that are ineffective for treatment of progressive multiple sclerosis.
Results from phase II and III trials suggest that the window of opportunity for treatment of progressive multiple sclerosis with anti-inflammatory drugs is predominantly in the early phase of the progressive disease course when patients have lower age, shorter duration of progressive multiple sclerosis, and more pronounced clinical and MRI inflammatory activity. Ongoing trials of neuroprotective drugs may widen the window of opportunity by expanding targeted pathophysiologies.
基于多发性硬化(MS)进展过程中疾病机制的相关知识,以及随机临床试验的经验,我们评估了进展型 MS 患者接受疾病修正治疗的时机,以确定治疗进展型 MS 的最佳时机。
在进展型 MS 中,能够穿透血脑屏障的小分子药物(西尼莫德)和单克隆抗体(奥瑞珠单抗)均显示出治疗效果,已被批准用于治疗进展型 MS。然而,进展型 MS 的大多数 II 期和 III 期临床试验结果为阴性,这可能是由于治疗开始较晚或使用了对进展型 MS 治疗无效的药物。
II 期和 III 期试验结果表明,用抗炎药物治疗进展型 MS 的时机主要在疾病进展的早期阶段,此时患者年龄较低、进展型 MS 的持续时间较短、临床和 MRI 炎症活动更明显。正在进行的神经保护药物试验可能通过扩大靶向病理生理学来拓宽治疗时机。