Early use of high-efficacy disease‑modifying therapies makes the difference in people with multiple sclerosis: an expert opinion

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.

Keywords: Disease progression; Disease-modifying drugs; Multiple sclerosis.

Fig. 1

Annualized relapse rate of each DMT relative to placebo. Annualized relapse rate network meta-analysis forest plot (versus placebo) with efficacy class for each disease-modifying therapies (2015 Association of British Neurologists guidelines). Rate ratios from the ARR NMA may not directly align with the relapse rate reduction values used by the ABN to group the DMTs. The ABN guidelines were published in 2015, so the NMA estimates were informed by additional more recently published trials. ABN Association of British Neurologists, ARR annualized relapse rate, DMT disease-modifying therapy, IFN interferon, IM intramuscular, NMA network meta-analysis, SC subcutaneous. Reproduced from Samjoo IA, Worthington E, Drudge C, Zhao M, Cameron C, Häring DA, Stoneman D, Klotz L, Adlard N. Efficacy classification of modern therapies in multiple sclerosis. J Comp Eff Res 2021; 10(6): 495–507. https://doi.org/10.2217/cer-2020-0267. An open-access article under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License