几乎所有目前获得许可的用于多发性硬化症治疗的疾病缓解疗法 (DMT) 都需要长期用药（即使不是终身用药）。然而，随着人们年龄的增长，免疫系统的反应能力日益降低，称为免疫衰老。许多 MS DMT 会降低免疫系统的反应性，增加感染和可能癌症的风险。随着 MS (pwMS) 患者年龄的增长，炎症性 MS 活性会下降。一些研究已经解决了特殊情况下针对复发性多发性硬化症的 DMT 降级问题。在此，我们回顾了降级 DMT 作为与老年 pwMS 特别相关的策略的证据。治疗降级可能涉及多种策略，例如延长或减少剂量、从风险较高的高效 DMT 转换为风险较低的中等有效的 DMT，或停止治疗。研究表明那他珠单抗延长剂量可维持临床疗效，同时降低 PML 风险。延长 ocrelizumab 的给药间隔可减轻 Ig 水平的下降。回顾性和观察性停药研究表明，年龄是药物疗效的重要调节因素。老年患者停止 MS 治疗与稳定的病程相关，而停止治疗的年轻患者更有可能经历新的临床活动。最近完成的一项为期 2 年的随机对照停药研究，涉及 260 个稳定的 pwMS >55 年，发现临床多发性硬化症稳定，停药后新 MRI 活动的风险仅略有增加。对于 55 岁以上的多发性硬化症患者，DMT 降级或停药可能并不劣于继续使用具有较高健康风险的免疫抑制剂治疗。然而，尽管进行了几项小型研究，但关于老年 pwMS 治疗降级的明确结论仍需要更大规模、更长期的研究。理想情况下，应通过前瞻性随机对照试验来比较 DMT 降级、继续或停止的比较，该试验招募足够数量的受试者，以便对年龄组（例如 55-59 岁、60-65 岁、60-65 岁）内的男女 MS 患者进行比较。 66-69 等。最佳情况下，此类研究应持续 3 年或更长时间，并应纳入针对免疫衰老的特定标记物（例如 T 细胞受体切除圈）的测试，以解释个体的衰老差异。© 2024。作者）。

Almost all currently licensed disease-modifying therapies (DMTs) for MS treatment require prolonged if not lifelong administration. Yet, as people age, the immune system has increasingly reduced responsiveness, known as immunosenescence. Many MS DMTs reduce the responsiveness of the immune system, increasing the risks for infections and possibly cancers. As people with MS (pwMS) age, it is recognized that inflammatory MS activity declines. Several studies have addressed de-escalation of DMTs for relapsing MS under special circumstances. Here, we review evidence for de-escalating DMTs as a strategy that is particularly relevant to pwMS of older age. Treatment de-escalation can involve various strategies, such as extended or reduced dosing, switching from high-efficacy DMTs having higher risks to moderately effective DMTs with lesser risks, or treatment discontinuation. Studies have suggested that for natalizumab extended dosing maintained clinical efficacy while reducing the risk of PML. Extended interval dosing of ocrelizumab mitigated the decline of Ig levels. Retrospective and observational discontinuation studies demonstrate that age is an essential modifier of drug efficacy. Discontinuation of MS treatment in older patients has been associated with a stable disease course, while younger patients who discontinued treatment were more likely to experience new clinical activity. A recently completed 2-year randomized-controlled discontinuation study in 260 stable pwMS > 55 years found stable clinical multiple sclerosis with only a small increased risk of new MRI activity upon discontinuation. DMT de-escalation or discontinuation in MS patients older than 55 years may be non-inferior to continued treatment with immunosuppressive agents having higher health risks. However, despite several small studies, a definite conclusion about treatment de-escalation in older pwMS will require larger and longer studies. Ideally, comparison of de-escalation versus continuation versus discontinuation of DMTs should be done by prospective randomized-controlled trials enrolling sufficient numbers of subjects to allow comparisons for MS patients of both sexes within age groups, such as 55-59, 60-65, 66-69, etc. Optimally, such studies should be 3 years or longer and should incorporate testing for specific markers of immunosenescence (such as T-cell receptor excision circles) to account for differential aging of individuals.© 2024. The Author(s).