• Demyelinating Diseases
• Neurology Clinical Trials

• Demyelinating Diseases
• Neurology
• Neurology Clinical Trials

Laquinimod, an oral immunomodulator under development for the treatment of multiple sclerosis (MS), reduced whole brain atrophy in the ALLEGRO and BRAVO trials [Vollmer T et al. Neurology. 2012]. In the ALLEGRO trial, laquinimod reduced the median percent volume change (PVC) in gray and white matter [Filippi M et al. J Neurol Neurosurg Psychiatry. 2014]. This study, presented by Kunio Nakamura, PhD, McGill University, Montreal, Canada, analyzed the effect of laquinimod on the PVC in gray and white matter in the phase 3 BRAVO trial [Vollmer T et al. J Neurol. 2014], using a newly developed, longitudinal image analysis technique.

In the BRAVO trial, 1331 patients with relapsing-remitting MS (RRMS) were randomized to oral laquinimod (n = 434), oral placebo (n = 450), or intramuscular interferon beta-1a (IFN-β-1a) (n = 447) for 24 months. The PVC from baseline in gray and white matter was measured at years 1 and 2 using pairwise Jacobian integration (PJI) [Nakamura K et al. Neuroimage Clin. 2013]. The subgroup analysis of PVC was based on baseline gadolinium-enhancing (Gd+) lesion counts and the PVC in gray and white matter.

Baseline characteristics were similar among the groups, except for the T2 lesion volume and the percentage of patients with Gd+ lesions, both of which were lower in the placebo group. Baseline normalized gray and white matter volumes were comparable among the groups.

The mean PVC in gray matter from baseline to year 1 was −0.609 with placebo, −0.797 with IFN-β-1a (−31% reduction vs placebo; P = .004), and −0.338 with laquinimod (51% reduction vs placebo; P < .001). The mean PVC in gray matter from baseline to year 2 was −1.199 with placebo, −1.348 with IFN-β-1a (−12% reduction vs placebo; P = .065), and −0.862 with laquinimod (28% reduction vs placebo; P < .001). The mean PVC in gray matter from year 1 to year 2 was −0.606 with placebo, −0.563 with IFN-β-1a (7% reduction vs placebo; P = .391), and −0.574 with laquinimod (5% reduction vs placebo; P = .422).

The mean PVC in white matter from baseline to year 1 was −0.453 with placebo, −0.541 with IFN-b-1a (−20% reduction vs placebo; P = .497), and −0.274 with laquinimod (40% reduction vs placebo; P = .001). The mean PVC in white matter from baseline to year 2 was −0.801 with placebo, −0.978 with IFN-b-1a (−22% reduction vs placebo; P = .180), and −0.665 with laquinimod (17% reduction vs placebo; P = .011). The mean PVC in white matter from year 1 to year 2 was −0.363 with placebo, −0.451 with IFN-b-1a (24% reduction vs placebo; P = .298), and −0.402 with laquinimod (−11% reduction vs placebo; P = .949).

Patients with baseline GD+ lesions had greater decreases in gray and white matter volumes. The treatment effect of laquinimod was consistent within Gd-based subgroups.

In this analysis, laquinimod reduced the percent volume decrease in gray and white matter from baseline to year 2 compared with placebo. The overall results were consistent with those in the ALLEGRO trial [Filippi M et al. J Neurol Neurosurg Psychiatry. 2014]. The PJI method was sensitive for detecting treatment effects.

• © 2014 MD Conference Express®