Plasma neurofilament light chain in children with relapsing MS receiving teriflunomide or placebo: A post hoc analysis of the randomized TERIKIDS trial

Abstract

Background: The phase 3 TERIKIDS study demonstrated efficacy and manageable safety for teriflunomide versus placebo in children with relapsing multiple sclerosis (RMS).

Objective: Evaluate plasma neurofilament light chain (pNfL) concentrations in TERIKIDS.

Methods: Patients received placebo or teriflunomide (14 mg adult equivalent) for up to 96 weeks in the double-blind (DB) period. In the open-label extension (OLE), all patients received teriflunomide until up to 192 weeks after randomization. pNfL was measured using single-molecule array assay (Simoa^® NF-light^™).

Results: Baseline mean age was 14.5 years; 69.4% were female. Baseline geometric least square mean pNfL levels were similar for teriflunomide (n = 78) and placebo (n = 33) patients (19.83 vs 18.30 pg/mL). Over the combined DB and OLE periods, pNfL values were lower for teriflunomide versus placebo (analysis of variance p < 0.01; Week 192: 10.61 vs 17.32 pg/mL). Observed between-group pNfL differences were attenuated upon adjustment for gadolinium (Gd)-enhancing or new/enlarged T2 lesion counts at DB Week 24. Higher baseline pNfL levels were associated with shorter time since first MS symptom onset, higher baseline Gd-enhancing lesion counts and T2 lesion volume, and increased hazard of high magnetic resonance imaging activity or clinical relapse during the DB period.

Conclusion: Teriflunomide treatment was associated with significantly reduced pNfL levels in children with RMS.

Clinicaltrials.gov identifier: NCT02201108.

Keywords: Neurofilament light chain; pediatric MS; teriflunomide.

Figure 1.

TERIKIDS study design. ^aEntry to OLE any time after initial PK run-in; a new run-in period (8 weeks) starts after entry to extension. ^bCriteria for high MRI activity to qualify for switch to the OLE treatment were ⩾9 new/enlarged T2 lesions at Week 36 or ⩾5 new/enlarged T2 lesions on each of two consecutive MRI scans at Weeks 36 and 48, or at Weeks 48 and 72. ^cDetermined by body weight category: patients who weighed 20–40 kg received 3.5 mg/day; patients >40 kg received 7 mg/day. ^dDetermined by a combination of body weight category and individually predicted PK parameters based on data collected during the run-in period: patients who weighed 20–40 kg received 7 mg/day if predicted PK parameters were equal to or less than the adult range of predicted parameters for a repeated dose of 7 mg, or received 3.5 mg/day if PK parameters were higher than the adult range; patients > 40 kg received 14 mg/day if PK parameters were equal to or less than the adult range of predicted parameters, or received 7 mg/day if PK parameters were higher than the adult range. EDSS = Expanded Disability Status Scale; MRI = magnetic resonance imaging; OLE = open-label extension; PK = pharmacokinetic; pNfL = plasma neurofilament light chain; R = randomization.

Figure 2.

The effect of teriflunomide versus placebo on pNfL levels over time in the TERIKIDS study ^*p < 0.05 between treatment groups. Geometric least square means and 95% CIs were obtained by exponentiating estimates from the mixed model for repeated measures analysis, which modeled the log-transformed pNfL concentration as response variable, and had treatment, visit, treatment-by-visit interaction, and age as covariates. ^aBL is DB Week 2. BL = baseline; CI = confidence interval; DB = double blind; OLE = open-label extension; pNfL = plasma neurofilament light chain.