Pathophysiology of multiple sclerosis and the place of teriflunomide

Abstract

Significant progress in multiple sclerosis (MS) treatment has been made over the last two decades, including the emergence of disease-modifying therapy (DMT). However, substantial unmet medical need persists and has stimulated the search for new therapeutics. Teriflunomide, one of the several oral DMTs under investigation, is a selective inhibitor of de novo pyrimidine synthesis which exerts a cytostatic effect on proliferating T- and B lymphocytes in the periphery and thus has both antiproliferative and anti-inflammatory properties. Anti-inflammatory effects have been demonstrated in rodent MS models, with reductions in macrophage and B- and T-cell infiltration in the central nervous system and preservation of myelin and oligodendrocytes. Delays in disease onset, reductions in disease relapses and improvements in clinical symptoms were also observed. A proof-of-concept clinical trial in patients with relapsing MS demonstrated that teriflunomide significantly reduced magnetic resonance imaging (MRI) activity and improved clinical endpoints, with both effects maintained with longer-term treatment. Additional studies have shown that teriflunomide can be safely added to beta interferon or glatiramer acetate therapy, with some evidence of additional improvements in MRI disease burden and clinical signs. Teriflunomide has an acceptable and manageable safety and tolerability profile. A large clinical programme is underway to further elucidate the role of teriflunomide in the treatment of MS.