Early high-efficacy therapy in multiple sclerosis: from conception to clinical practice Review article

Abstract

Disability progression in multiple sclerosis is driven by three main mechanisms: relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and age-related progression. Both RAW and PIRA contribute to smouldering-associated worsening (SAW), which underlies the gradual accumulation of disability.

Early initiation of high-efficacy treatment agents (HETA) helps prevent disability progression and limits the development of SAW. HETA are now considered the cornerstone of modern multiple sclerosis management and are increasingly recommended as first-line therapy. They should be initiated as early as possible after diagnosis, particularly in patients with poor prognostic factors.

Natalizumab, which has been used in the treatment of multiple sclerosis for more than 20 years, is a high-efficacy therapy with a unique mechanism of action. It is a humanized monoclonal antibody directed against the α4-integrin subunit expressed on the surface of leukocytes, thereby preventing their migration into the central nervous system.

Natalizumab may be considered in appropriately selected patients with highly active multiple sclerosis, particularly in the presence of poor prognostic factors, and in selected clinical situations such as relevant comorbidities, pregnancy planning, or the need for vaccination, after an individual benefit risk assessment. Early initiation of high-efficacy therapy, including natalizumab in appropriately selected patients, may contribute to improved disease activity control and reduced disability progression.