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Early use of high-efficacy disease‑modifying therapies makes the difference in people with multiple sclerosis: an
Massimo Filippi1,2,3,4,5, Maria Pia Amato6,7, Diego Centonze8,9
1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. filippi.massimo@hsr.it.
Abstract:
Multiple sclerosis (MS) is a chronic and progressive neurological disease that is characterized by neuroinflammation, demyelination and neurodegeneration occurring from the earliest phases of the disease and that may be underestimated. MS patients accumulate disability through relapse-associated worsening or progression independent of relapse activity. Early intervention with high-efficacy disease-modifying therapies (HE-DMTs) may represent the best window of opportunity to delay irreversible central nervous system damage and MS-related disability progression by hindering underlying heterogeneous pathophysiological processes contributing to disability progression. In line with this, growing evidence suggests that early use of HE-DMTs is associated with a significant greater reduction not only of inflammatory activity (clinical relapses and new lesion formation at magnetic resonance imaging) but also of disease progression, in terms of accumulation of irreversible clinical disability and neurodegeneration compared to delayed HE-DMT use or escalation strategy. These beneficial effects seem to be associated with acceptable long-term safety risks, thus configuring this treatment approach as that with the most positive benefit/risk profile. Accordingly, it should be mandatory to treat people with MS early with HE-DMTs in case of prognostic factors suggestive of aggressive disease, and it may be advisable to offer an HE-DMT to MS patients early after diagnosis, taking into account drug safety profile, disease severity, clinical and/or radiological activity, and patient-related factors, including possible comorbidities, family planning, and patients' preference in agreement with the EAN/ECTRIMS and AAN guidelines. Barriers for an early use of HE-DMTs include concerns for long-term safety, challenges in the management of treatment initiation and monitoring, negative MS patients' preferences, restricted access to HE-DMTs according to guidelines and regulatory rules, and sustainability. However, these barriers do not apply to each HE-DMT and none of these appear insuperable.
Insights
Early treatment with high-efficacy disease-modifying therapies (HE-DMTs) significantly reduces multiple sclerosis (MS) inflammation and disability progression. This approach offers the best benefit/risk profile for managing MS, despite some treatment barriers.
Area of Science:
- Neuroscience
- Immunology
- Neurology
Background:
- Multiple sclerosis (MS) is a chronic neurological disease marked by neuroinflammation, demyelination, and neurodegeneration, often underestimated in early stages.
- MS patients experience disability accumulation through relapses or progression independent of relapses.
Purpose of the Study:
- To evaluate the benefits of early intervention with high-efficacy disease-modifying therapies (HE-DMTs) in mitigating MS progression.
- To compare the efficacy and safety of early HE-DMT use versus delayed or escalated treatment strategies.
Main Methods:
- Review of current evidence on early HE-DMT use in MS management.
- Analysis of clinical and magnetic resonance imaging (MRI) outcomes associated with different treatment timings.
- Assessment of the benefit/risk profile and safety considerations of HE-DMTs.
Main Results:
- Early HE-DMT use is linked to greater reductions in inflammatory activity, including relapses and new MRI lesions.
- Initiating HE-DMTs early significantly slows irreversible clinical disability accumulation and neurodegeneration compared to delayed strategies.
- The beneficial effects of early HE-DMTs are associated with acceptable long-term safety, presenting a favorable benefit/risk profile.
Conclusions:
- Early initiation of HE-DMTs is crucial for managing MS, especially in patients with prognostic factors for aggressive disease.
- Guidelines recommend offering HE-DMTs early post-diagnosis, considering individual patient factors and drug profiles.
- Barriers to early HE-DMT use exist but are often surmountable, emphasizing the importance of timely and effective MS treatment.
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