Two randomized, double-blind clinical trials of oral laquinimod in relapsing–remitting multiple sclerosis (MS) have been completed. The BRAVO study failed to meet its primary end point, a significant decrease in annualized relapse rate (ARR), until a prespecified readjustment was carried out because of an imbalance in baseline characteristics. The ALLEGRO study, however, satisfied this end point.
Despite the adjustments, the effect of laquinimod on a reduction in ARR was only 21.3%, its effect on decrease in Expanded Disability Status Scale (EDSS) was 33.5%, and its effect on decrease in brain volume loss was 27.5%. No significant decrease in ARR or disability progression was found comparing placebo to interferon b-1a. Comparisons between interferon and laquinimod have not yet been published.
A post hoc analysis of the combined studies yielded results similar to those of the individual studies. Although it is dangerous to do a cross-study comparison, the laquinimod results compared unfavorably to those of other phase 3 trials in effect on ARR reduction, or decrease in Gad+ or new T2 lesions. The major positive findings were the effects of laquinimod in reducing sustained EDSS progression and loss of brain volume. This result raises the possibility that laquinimod may have a mechanism of action other than as an anti-inflammatory agent.