Treatment De-escalation in Relapsing-Remitting Multiple Sclerosis: An Observational Study.

IF 7.4 2区医学 Q1 CLINICAL NEUROLOGY

CNS drugs Pub Date : 2025-04-01 Epub Date: 2025-02-14 DOI:10.1007/s40263-025-01164-w

Jannis Müller, Sifat Sharmin, Johannes Lorscheider, Dana Horakova, Eva Kubala Havrdova, Sara Eichau, Francesco Patti, Pierre Grammond, Katherine Buzzard, Olga Skibina, Alexandre Prat, Marc Girard, Francois Grand'Maison, Raed Alroughani, Jeannette Lechner-Scott, Daniele Spitaleri, Michael Barnett, Elisabetta Cartechini, Maria Jose Sa, Oliver Gerlach, Anneke van der Walt, Helmut Butzkueven, Julie Prevost, Tamara Castillo-Triviño, Bassem Yamout, Samia J Khoury, Özgür Yaldizli, Tobias Derfuss, Cristina Granziera, Jens Kuhle, Ludwig Kappos, Izanne Roos, Tomas Kalincik

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引用次数: 0

Abstract

Background: In relapsing-remitting multiple sclerosis (RRMS), extended exposure to high-efficacy disease modifying therapy may increase the risk of side effects, compromise treatment adherence, and inflate medical costs. Treatment de-escalation, here defined as a switch to a lower efficacy therapy, is often considered by patients and physicians, but evidence to guide such decisions is scarce. In this study, we aimed to compare clinical outcomes between patients who de-escalated therapy versus those who continued their therapy.

Methods: In this retrospective analysis of data from an observational, longitudinal cohort of 87,239 patients with multiple sclerosis (MS) from 186 centers across 43 countries, we matched treatment episodes of adult patients with RRMS who underwent treatment de-escalation from either high- to medium-, high- to low-, or medium- to low-efficacy therapy with counterparts that continued their treatment, using propensity score matching and incorporating 11 variables. Relapses and 6-month confirmed disability worsening were assessed using proportional and cumulative hazard models.

Results: Matching resulted in 876 pairs (de-escalators: 73% females, median [interquartile range], age 40.2 years [33.6, 48.8], Expanded Disability Status Scale [EDSS] 2.5 [1.5, 4.0]; non-de-escalators: 73% females, age 40.8 years [35.5, 47.9], and EDSS 2.5 [1.5, 4.0]), with a median follow-up of 4.8 years (IQR 3.0, 6.8). Patients who underwent de-escalation faced an increased hazard of future relapses (hazard ratio 2.36 and 95% confidence intervals [CI] [1.79-3.11], p < 0.001), which was confirmed when considering recurrent relapses (2.43 [1.97-3.00], p < 0.001). It was also consistent across subgroups stratified by age, sex, disability, disease duration, and time since last relapse.

Conclusions: On the basis of this observational analysis, de-escalation may not be recommended as a universal treatment strategy in RRMS. The decision to de-escalate should be considered on an individual basis, as its safety is not clearly guided by specific patient or disease characteristics evaluated in this study.

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复发缓解型多发性硬化症治疗降级：一项观察性研究。

背景：在复发缓解型多发性硬化症（RRMS）中，长期接受高效的疾病修饰治疗可能会增加副作用的风险，降低治疗依从性，并增加医疗费用。治疗降级，在这里被定义为转向疗效较低的治疗，通常被患者和医生考虑，但指导这种决定的证据很少。在这项研究中，我们旨在比较降级治疗与继续治疗患者的临床结果。方法：对来自43个国家186个中心的87,239例多发性硬化症（MS）患者的观察性纵向队列数据进行回顾性分析，我们使用倾向评分匹配并纳入11个变量，将接受从高到中、高到低或中到低疗效治疗降级的成年RRMS患者的治疗发作与继续治疗的对照患者进行匹配。使用比例和累积风险模型评估复发和6个月确认的残疾恶化。结果：共匹配876对患者，其中女性占73%，年龄40.2岁[33.6,48.8]，扩展残疾状态量表[EDSS] 2.5 [1.5, 4.0]；非自动扶梯：73%女性，年龄40.8岁[35.5,47.9],EDSS 2.5岁[1.5,4.0])，中位随访时间4.8年（IQR 3.0, 6.8）。接受降级治疗的患者未来复发的风险增加（风险比2.36,95%可信区间[CI] [1.79-3.11], p < 0.001），在考虑复发时证实了这一点（2.43 [1.97-3.00],p < 0.001）。按年龄、性别、残疾、疾病持续时间和上次复发时间分层的亚组也一致。结论：基于这一观察性分析，可能不建议将降低风险作为RRMS的普遍治疗策略。应根据个人情况考虑降级的决定，因为在本研究中评估的特定患者或疾病特征并未明确指导其安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS drugs 医学-精神病学

CiteScore

12.00

自引率

3.30%

发文量

审稿时长

6-12 weeks

期刊介绍： CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.