Efficacy And Safety Of Tabalumab In Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study

Objective: This study (NCT00882999) evaluated the efficacy and safety of tabalumab in patients with relapsing-remitting multiple sclerosis (RRMS). Background: Tabalumab is a selective, fully human immunoglobulin G4 monoclonal antibody that neutralizes membrane-bound and soluble B-cell activating factor (BAFF). Inhibition of BAFF has been theorized as a therapeutic option in the treatment of RRMS. Design/Methods: This Phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group, dose-ranging, 73-week study included patients with RRMS who received tabalumab (4, 12, 40, or 120 mg every 4 weeks, or 4 or 120 mg every 12 weeks) or placebo subcutaneously. The primary endpoint, number of total cumulative gadolinium (Gd)-enhancing magnetic resonance imaging (MRI) lesions (whether new, pre-existing, unchanged, or enlarged from previous scans), summed over Weeks 12, 16, 20, and 24 was analyzed using one-way ANOVA model. Results: Of 245 randomized patients, 197 (80%) completed the study. The mean total numbers of Gd-enhancing MRI lesions averaged over Weeks 12, 16, 20, and 24 were 1.521 and 1.758 in the all-tabalumab and placebo groups, respectively; differences overall or between any of the tabalumab groups and placebo were not statistically significant. The proportion of patients reporting at least one treatment-emergent adverse event, serious adverse event, and follow-up emergent adverse event was higher in the all-tabalumab group than placebo (68.1% [n=143] vs 48.6% [n=17], 11% [n=23] vs 5.7% [n=2], and 41.9% [n=88] vs 34.3% [n=12], respectively); however, this was not dose dependent. Conclusions: Treatment with tabalumab was not efficacious in reducing Gd-enhancing MRI lesions in patients with RRMS versus placebo; no specific safety concern was identified. Study Supported by: Eli Lilly and Company Disclosure: Dr. Silk has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Nantz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company.