TERIKIDS trial extension of teriflunomide in paediatric MS

During the combined double-blind and open-label periods in the TERIKIDS-trial, continuous teriflunomide numerically lowered clinical relapses and the risk of 24-week sustained disability progression compared with delayed initiation of teriflunomide after placebo [1]. Teriflunomide was well tolerated and had a manageable safety profile.

TERIKIDS (NCT02201108) is a 2-year, multicentre, multinational, randomised, double-blind, placebo-controlled, parallel-group phase 3 study of teriflunomide in children and adolescents of 10-17 years at baseline with relapsing MS. It is followed by a 96-week open-label period, of which interim results were shared. All participants in the open-label period (n=152) received teriflunomide at a dose based on body weight, equivalent to 14 mg in adults.

The primary endpoint in the double-blind period, median time to first confirmed relapse, was 75.3 weeks with teriflunomide and 39.1 weeks with placebo (HR 0.66; 95% CI 0.39–1.1). This difference was not statistically significant versus placebo (P=0.29). In a prespecified sensitivity analysis, median time to first disease activity was significantly reduced by teriflunomide (HR 0.57; 95% CI 0.37-0.87; P=0.041).

Differences in key secondary outcomes were also significant. There was relative reduction of 75% in the number of T1 gadolinium-enhancing lesions versus placebo (P<0.0001), and a relative reduction of 55% in the number of new/enlarging T2 lesions (P=0.0006). Median time to first confirmed relapse in the double-blind and open-label period combined was numerically lower with continuous teriflunomide versus placebo/teriflunomide (HR 0.61), as was time to disability progression (HR 0.552; see Figure). The number of new/enlarging T2 lesions per MRI scan was reduced with continuous teriflunomide versus placebo/teriflunomide (6.3 vs 13.0; P=0.0006). The number of T1 gadolinium-enhancing lesions was 4.2 versus 1.9 (P=0.0106).

Incidence of adverse events during the open-label period was lower with continuous teriflunomide than with placebo/teriflunomide: 68.0% versus 82.7%. In 8 patients, adverse events (2 serious) led to treatment discontinuation during the open-label period.

Figure: Time to disability progression sustained for 24 weeks [1]

1. Chitnis T, et al. Teriflunomide efficacy and safety in pediatric patients with relapsing forms of MS: Interim analysis of open-label TERIKIDS trial extension. MSVirtual 2020, Abstract FC02.04.