Clinical Efficacy of Laquinimod 0.6 mg Once Daily in the Treatment of Worsening Relapsing-Remitting Multiple Sclerosis (Baseline EDSS >3) (P3.051) (2016)

BACKGROUND: In relapsing-remitting MS (RRMS), confirmed disability progression (CDP) is more detrimental to daily function in patients who have already reached an EDSS score >3 than in those progressing from lower scores. Laquinimod, with pronounced effects on disability-related outcomes, presents a promising treatment option for these patients. This subgroup may also be informative of potential treatment effects in patients with progressive disease.
OBJECTIVE: To determine the clinical efficacy of laquinimod 0.6 mg compared with placebo in RRMS patients with baseline EDSS >3.
METHODS: Pooled data from ALLEGRO and BRAVO trials (N=1990) were used in this post-hoc analysis. Endpoints included annualized relapse rate (ARR) and time to CDP sustained for 3 or 6 months. MRI endpoints included percent brain volume change (PBVC) and cumulative numbers of gadolinium-enhancing (GdE) and new T2 lesions at Months 12 and 24.
RESULTS: Overall, 655 patients (33[percnt]; laquinimod n=328, placebo n=327) had baseline EDSS >3 and mean (SD) baseline EDSS of 4.1 (0.7). One-quarter (24.9[percnt]) had received prior MS treatment. Compared with the EDSS ≤3 subgroup, patients with baseline EDSS >3 were older (41.3 vs 36.5 years) and had longer disease duration (5.2 vs 3.7 years) and lower brain volume (1547 vs 1601 cm3) at baseline. In these patients, laquinimod reduced ARR (25[percnt], P=.012), 3-month CDP (40[percnt], P=.0229), and 6-month CDP (53[percnt], P=.0083). Laquinimod also reduced PBVC (adjusted mean difference, 0.39 [95[percnt] CI 0.21-0.58]; P<.0001) and cumulative number of new T2 lesions (rate ratio, 0.75 [95[percnt] CI 0.59-0.96]; P=.021) vs placebo. The effect on cumulative number of GdE lesions was not statistically significant in this subgroup.
CONCLUSIONS: Laquinimod demonstrated significant benefits in relapse, disability, and MRI outcomes in patients with baseline EDSS >3. These findings support the beneficial effects of laquinimod in RRMS and ongoing evaluation of this drug in progressive forms of MS. Disclosure: Dr. Vollmer has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Genentech, Inc., Novartis, Ono Pharmaceutical, Teva Neuroscience, and XenoPort as a consultant. Dr. Comi has received personal compensation for activities with Teva, Novartis, Genzyme, Merck Serono, Biogen, Bayer, Actelion, Almirall, and Serono Symposia International Foundation. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH. Dr. Montalban has received personal compensation for activities with Actelion, Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck & Co., Inc., NeuroTex, Novartis, Octopharma, Receptos, and Roche Diagnostics Corporation as a speaker. Dr. Cutter has received personal compensation for activities with Apotek, Ascendis Pharma, Biogen Idec, Cleveland Clinic, and GlaxoSmithKline. Dr. Steinerman has received personal compensation for activities with Teva Neuroscience as an employee. Dr. Sasson has received personal compensation for activities with Teva Pharmaceutical Industries Ltd. as an employee. Dr. Gorfine has received personal compensation for activities with Teva Pharmaceuticals Inc. Dr. Knappertz has received personal compensation for activities with Teva Neuroscience as an employee.