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关于使用克拉屈滨片作为稳定期老年多发性硬化症患者退出治疗的叙述性综述。

Narrative Review on the Use of Cladribine Tablets as Exit Therapy for Stable Elderly Patients with Multiple Sclerosis.

作者信息

de Seze Jerome, Dive Dominique, Ayrignac Xavier, Castelnovo Giovanni, Payet Marianne, Rayah Amel, Gobbi Claudio, Vermersch Patrick, Zecca Chiara

机构信息

Department of Neurology, Strasbourg University Hospital, Strasbourg, France.

Department of Neurology, Liège University Hospital, Liège, Belgium.

出版信息

Neurol Ther. 2024 Jun;13(3):519-533. doi: 10.1007/s40120-024-00603-y. Epub 2024 Apr 8.

Abstract

The number of ageing people with relapsing multiple sclerosis (RMS) is increasing. The efficacy of disease-modifying therapies (DMTs) for RMS declines with age. Also, older persons with MS may be more susceptible to infections, hospitalisations and malignancy. Aging people with MS have higher rates of comorbidities versus aged-matched controls, increasing the individual risk of disability. We review the therapeutic properties of cladribine tablets (CladT) in ageing people with RMS, with regard to their utility for allowing these individuals to cease continuous administration of a DMT (i.e. to act as an "exit therapy"). CladT is thought to be an immune reconstitution therapy, in that two short courses of oral treatment 1 year apart provide suppression of MS disease activity in responders that far outlasts the duration of treatment and post-treatment reductions in lymphocyte counts. Post hoc analyses, long-term follow-up of populations with RMS in randomised trials, and real-world evidence suggest that the efficacy of CladT is probably independent of age, although more data in the elderly are still needed. No clear adverse signals for lymphopenia or other adverse safety signals have emerged with increasing age, although immunosenescence in the setting of age-related "inflammaging" may predispose elderly patients to a higher risk of infections. Updating vaccination status is recommended, especially against pneumococci and herpes zoster for older patients, to minimise the risk of these infections. CladT may be a useful alternative treatment for ageing people with MS who often bear a burden of multiple comorbidities and polypharmacy and who are more exposed to the adverse effects of continuous immunosuppressive therapy.

摘要

复发型多发性硬化症(RMS)老年患者的数量正在增加。疾病修正治疗(DMTs)对RMS的疗效会随着年龄增长而下降。此外,患有多发性硬化症的老年人可能更容易受到感染、住院和患恶性肿瘤。与年龄匹配的对照组相比,患有多发性硬化症的老年人共病率更高,这增加了个体的残疾风险。我们回顾了克拉屈滨片(CladT)在患有RMS的老年人中的治疗特性,以及其作为“退出疗法”使这些个体停止持续使用DMT的效用。CladT被认为是一种免疫重建疗法,因为相隔1年进行的两个短期口服疗程可抑制有反应者的MS疾病活动,其持续时间远远超过治疗期以及治疗后淋巴细胞计数的下降时间。事后分析、随机试验中RMS人群的长期随访以及实际证据表明,CladT的疗效可能与年龄无关,不过仍需要更多针对老年人的数据。随着年龄增长,尚未出现明显的淋巴细胞减少不良信号或其他不良安全信号,尽管在与年龄相关的“炎症衰老”背景下的免疫衰老可能使老年患者更容易感染。建议更新疫苗接种状态,尤其是老年患者的肺炎球菌和带状疱疹疫苗接种,以将这些感染的风险降至最低。对于患有多发性硬化症且常常承受多种共病和多种药物治疗负担、更容易受到持续免疫抑制治疗不良反应影响的老年人,CladT可能是一种有用的替代治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4684/11136913/179e7d8b9f3f/40120_2024_603_Fig1_HTML.jpg

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