Oral laquinimod therapy in relapsing multiple sclerosis.
BACKGROUND
Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS. Early treatment reduces the number of relapses, limits progression of disability, and improves quality of life; however, existing therapies are only partially effective and require parenteral administration.


OBJECTIVE
To review current experience with laquinimod as a novel immunomodulatory therapy for MS.


RESULTS
Laquinimod is a new quinolonecarboxamide that has demonstrated efficacy in animal models of several autoimmune diseases, including MS. It shows immunomodulatory effects, likely through Th1/Th2 shift, but does not lead to immunosuppression. Laquinimod is metabolized in the liver, primarily by the CYP3A4 enzyme. Phase II studies in relapsing MS demonstrate a dose-response effect on disease activity, measured by number of active lesions on brain magnetic resonance imaging, and show favorable tolerability and safety based on clinical and laboratory indicators. Two Phase III studies currently in progress are evaluating the efficacy of laquinimod 0.6 mg/day in relapsing MS. The drug was granted a fast track review by the FDA in 2009.


CONCLUSIONS
Laquinimod is a novel, orally administered immunomodulator that has advanced to the pre-submission stage and may become an alternative to the current injectable first-line treatments for relapsing MS.
Preiningerova
Jana
J
Yale Multiple Sclerosis Center, 40 Temple Street, New Haven, CT 06510, USA. jana.preiningerova@yale.edu
D000284:Administration, Oral; D000818:Animals; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015363:Quinolones / Q000008:administration & dosage*
D007155:Immunologic Factors; D015363:Quinolones; C476223:laquinimod