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Review
. 2024 Jan;271(1):105-115.
doi: 10.1007/s00415-023-11969-8. Epub 2023 Oct 18.

Multiple sclerosis: time for early treatment with high-efficacy drugs

Krzysztof Selmaj  1   2 , Bruce A C Cree  3 , Michael Barnett  4 , Alan Thompson  5 , Hans-Peter Hartung  4   6   7   8
Affiliations
Review

Multiple sclerosis: time for early treatment with high-efficacy drugs

Krzysztof Selmaj et al. J Neurol. 2024 Jan.

Abstract

This review addresses current changes in the approach to treating patients with multiple sclerosis (MS). The widely practiced approach of utilizing agents with lower treatment efficacy (LETA) at onset with subsequent escalation has been challenged by new data suggesting that MS patients derive greater benefit when therapy is initiated with high-efficacy treatment agents (HETA). Several recent studies compared treatment efficacy and safety of early administration of HETA versus LETA. The results of randomized, double blind, phase III studies with LETA as a control arm and population-based larger and longer studies using propensity scoring, marginal structural modeling and weighted cumulative exposure analysis support the benefit of early treatment with HETA. Patients initiating their treatment with HETA, regardless of prognostic factors and MRI burden at baseline, showed significantly lower annualized relapse rate (ARR) and reduced disability progression in follow-up periods of up to 10-15 years. Moreover, the safety profile of recently approved HETA ameliorates concerns about off-target effects associated with a number of earlier high-efficacy drugs. Patient perception has also changed with an increasing preference for medication profiles that both improve symptoms and prevent disease progression. Accumulating data from randomized studies and the results of large population-based studies demonstrating short-term and longer-term patient benefits support the view that HETA should be more widely used. The adoption of early treatment with HETA capitalizes on a window of opportunity for anti-inflammatory drugs to maximally impact disease pathology and heralds a sea change in clinical practice toward pro-active management and away from a philosophy routed in generating clinical benefit as a consequence of treatment failure.

Keywords: Escalation therapy; High-efficacy drugs; Multiple sclerosis; Safety.

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Conflict of interest statement

KS has received personal compensation for consulting from Biogen, Celgene, GeNeuro, Merck, Novartis, Polpharma, Sanofi, Roche, TG Therapeutics, and received research support from Merck and Roche. BC has received personal compensation for consulting from Alexion, Atara, Autobahn, Avotres, Biogen, EMD Serono, Horizon, Neuron23, Novartis, Sanofi, TG Therapeutics and Therini and received research support from Genentech. MB served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis. AT received personal compensation for consulting from Sandoz Global Advisory and Novartis; and has received fees (paid to institution) for serving on a steering committee for Eisai Co Ltd, HPH received fees for serving on steering and data monitoring committees from BayerHealthcare, Biogen, BMS Celgene, GeNeuro, Merck, Imcyse, Novartis, Roche, TG Therapeutics, VielaBio with approval by the Rector of Heinrich-Heine-University.

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