Treatment with laquinimod reduces development of active MRI lesions in relapsing MS.
BACKGROUND
Laquinimod is a novel immunomodulatory substance developed as an orally available disease modifying treatment in multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability, and efficacy on MRI lesions of two different doses of laquinimod compared with placebo in patients with relapsing MS.


METHODS
In this multicenter, double-blind, randomized trial, patients with relapsing MS received 0.1 mg or 0.3 mg laquinimod or placebo as three daily tablets for 24 weeks. Gadolinium-enhanced brain MRI scans were performed at screening, every eighth week during treatment, and 8 weeks after end of treatment. The primary efficacy variable was the cumulative number of active lesions over 24 weeks. Safety measures included adverse events, physical examination, and laboratory variables.


RESULTS
Of 256 screened patients, 209 were randomized (67 to 74 patients per group) in 20 centers. There was a significant difference between laquinimod 0.3 mg and placebo for the primary outcome measure (mean cumulative number of active lesions reduced by 44%). In the subgroup of patients with at least one active lesion at baseline the reduction was slightly more pronounced (52%). No differences with respect to clinical variables (relapses, disability) were found. The safety profile was favorable; there were no clinical signs of undesired inflammatory manifestations.


CONCLUSIONS
Oral laquinimod in a dosage of 0.3 mg daily was well tolerated and effective in suppressing development of active lesions in relapsing multiple sclerosis.
Polman
C
C
Department of Neurology, VU Medical Centre, Amsterdam, The Netherlands. ch.polman@vumc.nl
Barkhof
F
F
Sandberg-Wollheim
M
M
Linde
A
A
Nordle
O
O
Nederman
T
T
D000284:Administration, Oral; D000328:Adult; D002490:Central Nervous System / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D010919:Placebos; D015363:Quinolones; C476223:laquinimod