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Teriflunomide for multiple sclerosis

Disease-modifying therapies ( DMTs ) for multiple sclerosis aim to specifically reduce inflammation in relapsing multiple sclerosis and promote neuroprotection and neurorepair in progressive multiple sclerosis ( MS ). Most of the currently available disease-modifying drugs ( DMDs ) require regular and frequent parenteral administration, which imposes a burden on patients and leads to reduced adherence. Not all multiple sclerosis patients respond adequately to current DMDs and, therefore, alternative multiple sclerosis treatments with less invasive routes of administration and new modes of action are required to expand the current treatment repertoire, increase adherence, and thereby improve efficacy. As one of the oral DMDs, Teriflunomide ( Aubagio ) is a potentially promising new oral agent in the treatment of relapsing multiple sclerosis. It inhibits dihydro-orotate dehydrogenase ( DHODH ) and the synthesis of pyrimidine and has selective immunosuppressive and immunomodulatory properties.

A review has explored the potential benefits of teriflunomide and so expand the available DMT options, the effectiveness and safety of Teriflunomide, as monotherapy or combination therapy, were assessed versus placebo or approved DMDs ( IFN-beta, Glatiramer acetate, Natalizumab, Mitoxantrone, Fingolimod ) for modifying disease in patients with multiple sclerosis.

Selection criteria were all randomised, double-blind, controlled, parallel clinical trials ( RCTs ) with a length of follow-up of at least one year evaluating Teriflunomide, as monotherapy or combination therapy, versus placebo or other treatments for patients with multiple sclerosis.
Two review authors independently extracted data and assessed trial quality.

Two studies involving 1204 people evaluated the efficacy and safety of Teriflunomide 7 mg and 14 mg, alone or with add-on Interferon-beta, versus placebo for adult patients with relapsing forms of multiple sclerosis ( relapsing-remitting [ RRMS ], secondary progressive [ SPMS ] with relapse, and progressive relapsing multiple sclerosis [ PRMS ] ) and an entry Expanded Disability Status Scale ( EDSS ) score of less than or equal to 5.5.
Both studies had high attrition bias ( 26.8% and 36.4% attrition respectively ).
Teriflunomide 7 or 14 mg alone had potential benefits on reducing relapse rates, and alone or with add-on Interferon-beta was safe for patients with relapsing forms of multiple sclerosis in the short term. The most common adverse events included nasopharyngitis, headache, diarrhoea, fatigue, elevated alanine aminotransferase levels, nausea, hair thinning or decreased hair density, influenza, back pain, urinary tract infection, and pain in the arms or legs.

Researchers found low-level evidence for the use of Teriflunomide as a disease-modifying therapy for multiple sclerosis, due to the limited quality of the available RCTs.
Investigators did not conduct meta-analysis because of the clinical and methodological diversity of the included studies.
Short-term Teriflunomide, 7 or 14 mg alone or with add-on Interferon-beta, was safe for patients with relapsing multiple sclerosis.
Both teriflunomide 7 and 14 mg alone had potential benefits for patients with relapsing forms of multiple sclerosis.

RCTs with high methodological quality and longer periods of observation are needed to assess safety, disability progression, neuroprotection and quality of life. ( Xagena )

He D et al, Cochrane Database Syst Rev 2012;12:CD009882. doi: 10.1002/14651858.CD009882.pub2.