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Review
. 2024 Oct 16:17:17562864241284372.
doi: 10.1177/17562864241284372. eCollection 2024.

Beyond lines of treatment: embracing early high-efficacy disease-modifying treatments for multiple sclerosis management

Celia Oreja-Guevara  1   2 , Sergio Martínez-Yélamos  3 , Sara Eichau  4 , Miguel Ángel Llaneza  5 , Jesús Martín-Martínez  6 , Joaquín Peña-Martínez  7 , Virginia Meca-Lallana  8 , Ana María Alonso-Torres  9 , Ester Moral-Torres  10 , Jordi Río  11 , Carmen Calles  12 , Adrián Ares-Luque  13 , Lluís Ramió-Torrentà  14 , María Eugenia Marzo-Sola  15 , José María Prieto  16 , María Luisa Martínez-Ginés  17 , Rafael Arroyo  18 , María Ángeles Otano-Martínez  19 , Luis Brieva-Ruiz  20 , Montserrat Gómez-Gutiérrez  21 , Alfredo Rodríguez-Antigüedad  22 , Victoria Galán Sánchez-Seco  23 , Lucienne Costa-Frossard  24 , Miguel Ángel Hernández-Pérez  25 , Lamberto Landete-Pascual  26 , Montserrat González-Platas  27 , José E Meca-Lallana  28
Affiliations
Review

Beyond lines of treatment: embracing early high-efficacy disease-modifying treatments for multiple sclerosis management

Celia Oreja-Guevara et al. Ther Adv Neurol Disord. .

Abstract

Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional "first-line" and "second-line" treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS. During its development, there was a recognized need to further discuss the concept of treatment lines and the early use of heDMTs. Evidence from randomized controlled trials and real-world studies suggests that early heDMT initiation leads to improved clinical outcomes, including reduced relapse rates, slowed disease progression, and decreased radiological activity, especially in younger patients or those in early disease stages. Despite the historical belief that heDMTs involve more risks and adverse events compared to moderate-efficacy DMTs (meDMTs), some studies have reported comparable safety profiles between early heDMTs and meDMTs, though long-term safety data are still lacking. The review also addresses the need for a personalized approach based on patient characteristics, prognostic factors, and preferences, explores the importance of therapeutic inertia, and highlights the evolving landscape of international and national guidelines that increasingly advocate for early intensive treatment approaches. The article also addresses the challenges of ensuring access to these therapies and the importance of further research to establish long-term safety and effectiveness of DMTs in MS.

Keywords: high-efficacy disease-modifying treatments; multiple sclerosis; treatment approach.

Plain language summary

Choosing stronger treatments early on for better multiple sclerosis care Recent progress in treating multiple sclerosis (MS) has changed how doctors think about starting treatments, with more support now for using high-efficacy disease-modifying treatments (heDMTs) early on. This article talks about why starting heDMTs early can be good, what benefits it might bring, and what challenges there might be. It also mentions how the old way of categorizing treatments into “first-line” and “second-line” is becoming outdated. This discussion is based on the latest recommendations from the Spanish Society of Neurology. The article explains that starting heDMTs early can lead to better results for patients, like fewer relapses, slower progression of the disease, and less damage seen on magnetic resonance imaging (MRI). This is particularly true for younger patients or those who are in the early stages of MS. Even though there was a concern that these heDMTs might have more side effects compared to other treatments, recent studies show that they could be just as safe, though more research is needed to be sure about their safety in the long run. The review suggests that treatment should be tailored to each patient, considering their specific situation, what they prefer, and the urgency to start treatment. It also discusses the need to overcome delays in starting these treatments and how treatment guidelines are changing to support starting strong treatments earlier. Finally, the article points out that it is still important to make these treatments accessible to everyone who needs them and to keep researching to understand their long-term safety and effectiveness.

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Figures

Figure 1.
Figure 1.
Arguments for the escalation approach and for early use of heDMTs. heDMTs, high-efficacy disease-modifying therapies.
Figure 2.
Figure 2.
Considerations for an early use of heDMTs in patients with MS as recommended by the Spanish MS guidelines. Source: Figure modified from Meca-Lallana et al. (2024). *Check prognostic factors on Table 2 (not all factors have the same specific weight in decision-making). ¥Note that some S1P modulators can be started when only one relapse has occurred and no poor prognosis factors are present, according to their Summary of Product Characteristics. heDMT, high-efficacy disease-modifying therapies; MS, multiple sclerosis; S1P, sphingosine-1-phosphate.
See this image and copyright information in PMC

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