Pipek Leonardo Zumerkorn, Mahler João Vitor, Nascimento Rafaela Farias Vidigal, Apóstolos-Pereira Samira Luísa, Silva Guilherme Diogo, Callegaro Dagoberto
Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, SP, BR, Av. Dr. Arnaldo, 455 - Cerqueira César, São Paulo, SP 01246-903, Brazil.
Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, SP, BR, Av. Dr. Arnaldo, 455 - Cerqueira César, São Paulo, SP 01246-903, Brazil.
Mult Scler Relat Disord. 2023 Mar;71:104581. doi: 10.1016/j.msard.2023.104581. Epub 2023 Feb 16.
The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with low- to moderate-efficacy disease-modifying drugs (DMDs) and upscale to high-efficacy DMDs when noting some evidence of active disease. Another approach, the early intensive (EIT) strategy, is starting with high-efficiency DMDs as first-line therapy. Our goal was to compare effectiveness, safety, and cost of ESC and EIT strategies.
We searched MEDLINE, EMBASE and SCOPUS until September 2022, for studies comparing EIT and ESC strategies in adult participants with relapsing-remitting MS and a minimum follow-up of 5 years. We examined the Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year period. Random-effects meta-analysis summarized the efficacy and safety and an EDSS-based Markov model estimated the cost.
Seven studies with 3,467 participants showed a 30% reduction in EDSS worsening in 5 years (RR 0.7; [0.59-0.83]; p < 0.001) in the EIT group vs in the ESC group. Two studies with 1,118 participants suggested a similar safety profile for these strategies (RR 1.92; [0.38-9.72]; p = 0.4324). EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and cladribine demonstrated cost-effectiveness in our model.
EIT presents higher efficacy in preventing disability progression, a similar safety profile, and can be cost-effective within a 5-year timeline.
多发性硬化症(MS)的最佳治疗策略一直存在争议。传统方法是逐步升级(ESC)策略,即从低至中等疗效的疾病修正药物(DMDs)开始,当发现有活动性疾病的某些证据时升级到高疗效DMDs。另一种方法是早期强化(EIT)策略,即从高效DMDs作为一线治疗开始。我们的目标是比较ESC和EIT策略的有效性、安全性和成本。
我们检索了MEDLINE、EMBASE和SCOPUS直至2022年9月,以寻找比较EIT和ESC策略在复发缓解型MS成年参与者中的研究,且最短随访期为5年。我们检查了扩展残疾状态量表(EDSS)、严重不良事件的比例以及5年期间的成本。随机效应荟萃分析总结了疗效和安全性,基于EDSS的马尔可夫模型估计了成本。
七项涉及3467名参与者的研究显示,EIT组与ESC组相比,5年内EDSS恶化降低了30%(风险比0.7;[0.59 - 0.83];p < 0.001)。两项涉及1118名参与者的研究表明这些策略的安全性相似(风险比1.92;[0.38 - 9.72];p = 0.4324)。在我们的模型中,使用延长给药间隔的那他珠单抗、利妥昔单抗、阿仑单抗和克拉屈滨的EIT显示出成本效益。
EIT在预防残疾进展方面具有更高的疗效,安全性相似,并且在5年时间内可能具有成本效益。