Title:From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis
Volume: 15
Issue: 6
Author(s): Lilian Aly, Bernhard Hemmer*Thomas Korn*
Affiliation:
- Department of Neurology, Technische Universität München, Ismaningerstraße 22, 81675 Munich,Germany
- Department of Neurology, Technische Universität München, Ismaningerstraße 22, 81675 Munich,Germany
Keywords:
Disease modifying therapy, immunosuppression, leflunomide, multiple sclerosis, oral, teriflunomide.
Abstract: Background: Immunosuppressive drugs have been used in the treatment of multiple
sclerosis (MS) for a long time. Today, orally available second generation immunosuppressive agents
have been approved or are filed for licensing as MS therapeutics. Due to semi-selective targeting of
cellular processes, these second-generation immunosuppressive compounds might rather be
immunomodulatory. For example, Teriflunomide inhibits the de novo pyrimidine synthesis and thus
only targets rapidly proliferating cells, including lymphocytes. It is used as first line disease
modifying therapy (DMT) in relapsing-remitting MS (RRMS).
Methods: Review of online content related to oral immunosuppressants in MS with an emphasis on
Teriflunomide.
Results: Teriflunomide and Cladribine are second-generation immunosuppressants that are efficient
in the treatment of MS patients. For Teriflunomide, a daily dose of 14 mg reduces the annualized
relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo.
Cladribine reduces the ARR by about 50% compared to placebo but has not yet been licensed due to
unresolved safety concerns. We also discuss the significance of older immunosuppressive compounds
including Azathioprine, Mycophenolate mofetile, and Cyclophosphamide in current MS therapy.
Conclusion: Teriflunomide has shown a favorable safety and efficacy profile in RRMS and is a
therapeutic option for a distinct group of adult patients with RRMS.
