停止多发性硬化症的疾病改良治疗:现实世界研究的系统综述和荟萃分析。

IF 7.4 2区 医学 Q1 CLINICAL NEUROLOGY
CNS drugs Pub Date : 2023-10-01 Epub Date: 2023-09-23 DOI:10.1007/s40263-023-01038-z
Luca Prosperini, Shalom Haggiag, Serena Ruggieri, Carla Tortorella, Claudio Gasperini
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引用次数: 0

摘要

背景:多发性硬化症是否需要终身疾病改良治疗(DMTs)的问题仍未得到解答。一些研究表明,患有稳定疾病的老年患者可以安全地停止DMT,但全面的循证数据很少,现实世界的研究提供了喜忧参半的结果。目的:本研究的目的是评估多发性硬化症患者停用DMTs后疾病再激活率和相关风险因素。方法:我们搜索科学数据库(PubMed/MEDLINE、Scopus和Google Scholar),以确定截至2023年7月31日发表的真实世界研究,这些研究报告了在中断治疗超过12个月后出现复发和/或残疾增加(感兴趣的结果)的患者人数。磁共振活性和DMT停药后重新开始治疗也被认为是额外的结果。我们排除了那些停药与意外或计划怀孕或在治疗转换之前明确相关的研究。我们进行了随机效应荟萃分析、亚组分析和元回归模型,以提供停药后复发和残疾事件的汇总估计,并确定其潜在的调节因素(预测因素)。结果:经过独立筛选,22篇文章符合资格标准,产生2942名患者的合并样本量,在停药后随访1-7年(11689名患者年)。复发和残疾事件的合并率分别为每100名患者年6.7和5.8。然而,现有数据无法使我们将孤立的残疾累积与复发相关的恶化区分开来。包括老年患者(β=-0.65,p=0.006)、DMTs暴露时间较长的患者(β=2.22,p=0.001)和疾病稳定期较长(β=2.74,p=0.002)的研究显示,复发事件的风险较低。根据元回归方程,DMT停药后复发事件的风险变得可以忽略不计(任意设定为结论:根据我们对真实世界数据的定量综合,在临床试验没有明确答案的情况下,DMT停药在选定的患者中似乎是可行的,具有高度的确定性。虽然我们的研究结果对复发事件是可靠的,但有必要在未来努力确定DMT停用药是否与孤立的残疾有关权责发生制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Stopping Disease-Modifying Treatments in Multiple Sclerosis: A Systematic Review and Meta-Analysis of Real-World Studies.

Stopping Disease-Modifying Treatments in Multiple Sclerosis: A Systematic Review and Meta-Analysis of Real-World Studies.

Background: The question of whether multiple sclerosis requires life-long disease-modifying treatments (DMTs) remains unanswered. Some studies suggest that older patients with stable disease may safely discontinue their DMTs, yet comprehensive evidence-based data are scarce and real-world studies have provided mixed results.

Objective: The aim of this study was to assess the rate of disease reactivation and associated risk factors after discontinuation of DMTs in patients with multiple sclerosis.

Methods: We searched scientific databases (PubMed/MEDLINE, Scopus and Google Scholar) to identify real-world studies published until 31 July, 2023 that reported the number of patients who experienced relapses and/or disability accrual (outcomes of interest) following a therapy discontinuation longer than 12 months. Magnetic resonance activity and treatment re-start after DMT discontinuation were also considered as additional outcomes. We excluded studies where therapy discontinuation was explicitly related to an unintended or planned pregnancy or preceded a treatment switch. We ran random-effects meta-analyses, subgroup analyses and meta-regression models to provide pooled estimates of post-discontinuation relapse and disability events, and to identify their potential moderators (predictors).

Results: After an independent screening, 22 articles met the eligibility criteria, yielding a pooled sample size of 2942 patients followed for 1-7 years after discontinuation (11,689 patient-years). The pooled rates for relapse and disability events were 6.7 and 5.8 per 100 patient-years, respectively. However, available data did not allow us to disentangle isolated disability accrual from relapse-associated worsening. Studies including older patients (β = -0.65, p = 0.006), patients with a longer exposure to DMTs (β = -2.22, p = 0.001) and patients with a longer period of disease stability (β = -2.74, p = 0.002) showed a lower risk of relapse events. According to meta-regression equations, the risk of relapse events after DMT discontinuation became negligible (arbitrarily set at < 1% per year) at approximately 60 years of age, and after either 10 years of DMT exposure, or 8 years of disease stability. Additional analyses showed pooled rates for magnetic resonance imaging activity and re-start events of 16.7 and 17.5 per 100 patient-years, respectively.

Conclusions: Based on our quantitative synthesis of real-world data, in the absence of definitive answers from clinical trials, DMT discontinuation appears feasible with a high degree of certainty in selected patients. While our findings are robust regarding relapse events, future efforts are warranted to determine if DMT discontinuation is associated with isolated disability accrual.

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来源期刊
CNS drugs
CNS drugs 医学-精神病学
CiteScore
12.00
自引率
3.30%
发文量
82
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.
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