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Laquinimod is rapidly absorbed following oral administration with bioavailability of 82%-95%. Two Phase 2 clinical trials were conducted with laquinimod. Both demonstrated a reduction in the frequency of gadolinium (Gd)-enhancing lesions and relapses in patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Laquinimod was well tolerated in both Phase 2 trials with few side effects. There was no difference in the overall number of adverse events (AEs) or serious adverse events (SAEs) between the placebo and laquinimod groups. Laquinimod effectively ameliorates both acute and chronic experimental autoimmune encephalomyelitis (EAE) decreasing both demyleination and axonal loss. Laquinimod may have protective effects on axonal integrity beyond that associated with decreased inflammation. Laquinimod has no immuno suppressive effects in animal models or in human studies, and does not decrease the ability of animals to mount a cellular or humeral immune response. The safety profile of laquinimod appears quite favorable.
Disease modifying therapy (DMT) with one of the approved agents should be considered in all patients with active relapsing-remitting multiple sclerosis (RRMS) once the diagnosis of MS is confirmed and in selected patients with a clinically isolated demyelinating syndrome (CIS). Interferon beta modulates T-cell and B-cell function, decreases expression of matrix metalloproteinases reversing blood-brain barrier disruption, and alters expression of cytokines. A series of double-blind, placebo-controlled Phase 3 trials in RRMS supported the benefit of interferon in reducing relapses, disability progression, and MRI lesion activity and accrual. All of the available agents have been reported to reduce relapse rate, magnetic resonance imaging (MRI) lesion activity, and accumulation of disability in RRMS. Patients need to be seen on a regular basis after starting treatment to address potential side effects. This chapter discusses treatment of acute relapses, progressive multiple sclerosis and treatment in special populations including children.
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