When to start, switch, and stop MS therapy: Real-world evidence counts

Real-world data provide supplementary information on: a) the importance of starting a disease-modifying therapy (DMT) early in multiple sclerosis (MS), b) on switching to high-efficacy DMT when moderate-efficacy DMT cannot stabilise the disease, and c) on starting high-efficacy DMT as first treatment, and stopping MS therapy in later stages of MS.

Randomised-controlled trials may be the gold standard of evidence but real-world data provides important supplementary data on DMTs in MS. “Although real-world research lacks blinding and randomisation, it uses unselected populations of patients, under real circumstances, with very different lifestyles and comorbidities, and can follow them for a long time,” argued Prof. Melinda Magyari (Rigshospitalet, Denmark) [1].

Possible real-world data sources are disease registries, databases, administrative claim data, medical records, big data, and (hopefully in the future) wearable devices. A critical issue real-world data can help clarify is when to start treatment with a DMT. This data is better suited than clinical trials to evaluate the ability of a DMT to postpone long-term disability. For example, a study Prof. Magyari co-authored, found that patients treated later (2–8 years after MS onset) were 42% more likely to reach an Expanded Disability Status Scale (EDSS) score of 6 than patients treated early (<2 years after disease onset; P=0.001) [2].

Real-world data has also shed light on the beneficial effects of starting high-efficacy DMT early in MS. These beneficial effects and the studies that found them were summarised in a very recent expert opinion paper [3]. This document claims it may be advisable to offer a high-efficacy DMT to MS patients early after diagnosis, taking into account factors such as drug safety profile, disease severity, clinical and/or radiological activity, and patient-related factors.

Prof. Magyari also addressed the question when to stop MS therapy. Reasons to do this include long disease duration, lack of relapses and of MRI activity, progression to secondary-progressive MS (SPMS) with very slow progression, safety issues, and access-related issues [4]. There are legitimate arguments for and against continuing DMT [5]. Prof. Magyari cited a study that identified a subset of patients with a high likelihood to stay relapse-free after discontinuing DMT: age >45 years at discontinuation, absence of relapses for ≥4 years on DMT before discontinuation, and absence of contrast-enhancing lesions [6].

Prof. Magyari concluded: “As the effectiveness of DMTs diminishes with time and MS progression, we should remember that the window of opportunity to treat the disease effectively is at its early stages. Timing of high-efficacy DMT has a long-term impact. Observational studies provide important supplementary data on this. We should always continue to monitor treatment effects. Permanent discontinuation of treatment may be appropriate in some cases.”

1. Magyari M, et al. Real-World-Evidence (Big data, registries): “game-changer” for regulatory and clinical views on when to start, switch and stop of disease-modifying therapies in MS? SYMP02-4, EAN 2022, 25–28 April, Vienna, Austria.
2. Chalmer TA, et al. Eur J Neurol. 2018;25(10):1262–70.
3. Filipp M, et al. J Neurol. May 24 2022. DOI: 10.1007/s00415-022-11193-w.
4. Hartung HP, et al. Curr Opin Neurol. 2021;34(4):598–603.
5. Knox KB, et al. Int J MS Care. 2020;22(2):75–84.
6. Bsteh G, et al. Mult Scler. 2017;23(9):1241–8.

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Posted on 22 August 2022