Multiple sclerosis (MS) is the most common chronic non-traumatic neurological disease in young adults, affecting over 2.8 million people worldwide. Its management has changed radically in the last 15 years with the introduction of high-efficacy disease-modifying therapies (HE-DMT). In 2026, the paradigm has shifted from conservative step-up therapy to the "hit hard, hit early" strategy: aggressive treatment from diagnosis to preserve neurological reserve.
Classification and pathophysiology
MS is an autoimmune central nervous system disease characterized by inflammation, demyelination, and axonal loss. Main clinical forms include relapsing-remitting MS (RRMS, 85% at onset), secondary progressive MS (SPMS), and primary progressive MS (PPMS, 15% of cases). The McDonald 2017 criteria allow diagnosis after a single clinical episode if MRI criteria for dissemination in space and time are met, accelerating initiation of disease-modifying treatment.
High-efficacy therapies: the new standard
The most effective DMTs for reducing annualized relapse rate (ARR) and disability progression are four drug families:
- Natalizumab (Tysabri): anti-α4-integrin antibody. Reduces ARR by 68% and disability progression by 42%. Monthly IV infusion. Main risk: progressive multifocal leukoencephalopathy (PML) from JC virus.
- Alemtuzumab (Lemtrada): anti-CD52 antibody producing deep lymphodepletion followed by immune reconstitution. Two treatment cycles separated by one year. Risk of secondary autoimmune diseases in 30-40% of patients.
- Ocrelizumab (Ocrevus): anti-CD20 antibody depleting B lymphocytes. IV every 6 months. First therapy approved for both RRMS and PPMS.
- Ofatumumab (Kesimpta): monthly subcutaneous anti-CD20. Equivalent efficacy to ocrelizumab with the advantage of home self-administration.
"Hit early, hit hard" strategy: evidence for a paradigm shift
The MSBase study, with over 14,000 patients, demonstrates that early treatment with HE-DMT reduces the risk of accumulated disability at 10 years by 60% compared to step-up therapy. The opportunity window is the first 5 years after diagnosis, when inflammation outweighs neurodegeneration.
MS and pregnancy
Pregnancy produces a natural reduction in relapses (especially in the third trimester), but the postpartum period carries a 20-30% increased relapse risk. Natalizumab can be maintained until week 30 of gestation and restarted in the immediate postpartum period. The 2024 European Academy of Neurology guidelines provide detailed recommendations for periconceptional management.
