期刊
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
卷 12, 期 6, 页码 701-709出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17425255.2016.1179279
关键词
Cytokines; demyelination; immunomodulation; laquinimod; neuroprotection; MRI
资金
- Bayer Halthcare
- Biogen Idec
- Genzyme
- Novartis
- Teva
- Sanofi
Introduction: Laquinimod is a new once-daily oral administrable agent, which is under investigation in a phase 3 clinical trial for relapsing remitting multiple sclerosis (RRMS) and in a phase 2 clinical trial for primary progressive MS (PPMS). Areas covered: The pharmacokinetic, pharmacodynamic and the safety profiles of laquinimod are covered in this review. In preclinical studies, the ability to prevent both experimental autoimmune encephalomyelitis and experimental autoimmune neuritis has been demonstrated. Reduced cell infiltration, demyelination, axonal damage and a shift of T-helper cell responses have been shown. Accordingly, in human studies, a decrease of pro-inflammatory and an increase of anti-inflammatory cytokines have been measured and a significant reduction of disease progression and a decrease in brain volume loss has been demonstrated. During all clinical studies a favorable safety profile was observed for 0.6mg laquinimod. New information about cardiovascular events is prompting the discontinuation of higher dosing regimens in both ongoing trials. Expert opinion: Laquinimod is a first in class oral agent with high potential to reduce disease progression in RRMS and PPMS. Owing to its favorable safety profile, a combination with 0.6mg laquinimod and other disease modifying therapies could be an option in future MS therapy.
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