Summary
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. Acta Neurol Scand. 2010 Sep 29. doi: 10.1111/j.1600-0404.2010.01444.x. [Epub ahead of print]Gold R, Wolinsky JS.
Details
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.