Teriflunomide in pediatric patients with relapsing multiple sclerosis: Open-label extension of TERIKIDS

Abstract

Background: The double-blind TERIKIDS study demonstrated the efficacy and safety of teriflunomide.

Objective: To evaluate the efficacy, safety, and tolerability of continuous teriflunomide treatment in the TERIKIDS open-label extension.

Methods: In the double-blind period, children with relapsing MS were randomized to placebo or teriflunomide (14 mg adult-equivalent dose) for ⩽ 96 weeks. Participants received teriflunomide for ⩽ 192 weeks post-randomization in the open-label extension.

Results: The mean age at screening was 14.6 years. For teriflunomide/teriflunomide versus placebo/teriflunomide, estimated clinical relapse risk was reduced by 38% (hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.39-0.98; p = 0.11) and numbers of gadolinium-enhancing T1 and new/enlarging T2 lesions were reduced by 43% (relative risk (RR) 0.570; 95% CI 0.33-0.98; p = 0.043) and 49% (RR 0.511; 95% CI 0.34-0.76; p = 0.001), respectively, in the combined double-blind and open-label periods. There was a trend toward reduced risk of 24-week sustained disability progression for teriflunomide/teriflunomide versus placebo/teriflunomide (HR 0.47; 95% CI 0.23-0.96). During the open-label extension, incidences of safety-related discontinuations were 4.0% (teriflunomide/teriflunomide) and 13.5% (placebo/teriflunomide), including two children who developed pancreatitis in the teriflunomide/teriflunomide group.

Conclusion: Teriflunomide reduced the long-term risk of focal inflammatory activity, with generally manageable tolerability and no new safety signals. Further evidence would strengthen clinical efficacy findings.ClinicalTrials.gov: NCT02201108.

Keywords: Teriflunomide; adolescent; child; clinical trial; relapsing multiple sclerosis; safety analysis.

Figure 1.

TERIKIDS participant disposition. DB: double blind; OLE: open-label extension.

Figure 2.

Time to first clinical relapse^a, combined double-blind and open-label extension periods. CI: confidence interval; HR: hazard ratio. ^aClinical relapse occurring in the double-blind period was adjudicated by the relapse adjudication panel. If the relapse happened in the open-label period, it was confirmed by objective signs on neurological examination (i.e., the basis for the relapse adjudication panel confirming relapses). ^bDerived using Cox proportional-hazards model with treatment group, region, pubertal status, age, and number of relapses in the year prior to randomization as covariates and with robust variance estimation. ^cDerived from log-rank test with stratification of region and pubertal status. North Africa and North America were combined for region stratum due to the small sample size.

Figure 3.

MRI outcomes, combined double-blind and open-label extension periods. CI: confidence interval; Gd: gadolinium; MRI: magnetic resonance imaging. ^aNegative binomial regression model with robust variance estimation, with total number of T1 Gd-enhancing lesions as response variable, with baseline, treatment group, region, pubertal status, and age as covariates and log-transformed number of scans as an offset variable. ^bNegative binomial regression model with robust variance estimation, with total number of T2 lesions as response variable, with treatment group, region, pubertal status, and age as covariates and log-transformed number of scans as an offset variable.

Figure 4.

Time to disability progression sustained for 24 weeks, combined double-blind and open-label extension periods.^a CI: confidence interval; EDSS: Expanded Disability Status Scale; HR: hazard ratio. ^aThe first sustained disability progression (i.e., confirmed disability worsening) is defined as a sustained increase of at least 1.0 point (0.5 for participants with baseline EDSS > 5.5) persisting for at least 24 weeks from baseline EDSS during combined double-blind and open-label extension treatment periods. ^bDerived using the Cox proportional-hazards model with treatment group, region, and pubertal status as covariates, offset by the lengths of individual observations. North Africa and North America were combined for region stratum due to the small sample size.