A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis

Abstract

Background: Teriflunomide is a once-daily oral immunomodulator for the treatment of relapsing-remitting MS.

Objective: To evaluate the safety and tolerability of teriflunomide as add-on therapy to a stable dose of glatiramer acetate (GA) in patients with relapsing forms of MS (RMS).

Methods: Phase II, randomized, double-blind, add-on, placebo-controlled study. The primary objective was to assess safety and tolerability; secondary objectives were to evaluate effects of treatment on disease activity assessed by MRI and relapse.

Results: Patients with RMS on GA (N = 123) were randomized 1:1:1 to receive teriflunomide 14 mg (n = 40), 7 mg (n = 42), or placebo (n = 41) for 24 weeks; 96 patients entered the 24-week extension, remaining on original treatment allocation. Teriflunomide was well tolerated over 48 weeks. The frequency of adverse events (AEs) was low across all groups; 5 (12.2%), 3 (7.1%), and 2 (5.0%) patients in the 14 mg, 7 mg, and placebo groups, respectively, discontinued treatment due to AEs. Teriflunomide reduced the number of T1-Gd lesions vs placebo (14 mg: 46.6% relative reduction, p = 0.1931; 7 mg: 64.0%: relative reduction, p = 0.0306).

Conclusions: Teriflunomide added to stable-dose GA had acceptable safety and tolerability, and reduced some MRI markers of disease activity compared with GA alone. NCT00475865 (core study); NCT00811395 (extension).

Keywords: MRI; Randomized clinical trial; multiple sclerosis; relapsing − remitting multiple sclerosis; safety.

Figure 1.

Study disposition GA = glatiramer acetate.

Figure 2.

MRI outcomes of teriflunomide as an adjunct to glatiramer acetate (mITT population). (a) Number of Gd-enhancing T1 (T1-Gd) lesions per scan at 24 and 48 weeks (the total number of T1-Gd lesions that occurred during the study divided by the total number of scans during the study, adjusted for baseline number of T1-Gd lesions, treatment, and region using a Poisson model with robust variance estimation). Error bars represent 95% confidence intervals. (b) Volume of T1-Gd lesions per scan at 24 and 48 weeks. The total volume of lesions that occurred during the study divided by the total number of scans during the study. GA = glatiramer acetate; Gd = gadolinium; mITT = modified intent-to-treat; RR = relative reduction.