Background

Teriflunomide is a once-daily oral immunomodulator approved for treating relapsing multiple sclerosis (RMS) and relapsing-remitting MS, depending on the local label. Efficacy and safety of teriflunomide were established in the phase 2 (NCT01487096) and phase 3 trials of patients with RMS (TEMSO [NCT00134563], TOWER [NCT00751881], TENERE [NCT00883337]) and clinically isolated syndrome (TOPIC [NCT00622700]). In post hoc analysis of TEMSO patients stratified by age, structural image evaluation using normalization of atrophy (SIENA) revealed teriflunomide 14 mg significantly reduced the percentage of brain volume change in patients aged >25 to ≤35 years (48%; P=0.0217) and >45 to ≤55 years (35%; P=0.0092) versus placebo over 2 years.

Objectives

To analyze the effect of teriflunomide treatment on MRI lesion activity in TEMSO study patients with RMS stratified by age.

Methods

In TEMSO, patients were randomized 1:1:1 to receive either placebo or teriflunomide 7 mg or 14 mg for ≤108 weeks (Year 2). Through Year 2, MRI lesion activity (unique combined active lesions [UCAL], contrast-enhancing T1 weighted lesions [CEL], and T2 weighted [T2w] lesions) and safety were assessed in the SIENA analysis subgroup; patients were stratified by age at baseline: ≥18 to ≤25 years (n=97 [10%]); >25 to ≤35 years (n=283 [29%]); >35 to ≤45 years (n=388 [40%]); and >45 to ≤55 years (n=201 [21%]). P values between treatment groups were determined for MRI lesions using a Poisson model.

Results

Of 1086 patients in the TEMSO core study, 969 (89%) had scans appropriate for SIENA analysis. Compared with placebo, teriflunomide 14 mg significantly reduced the number of UCAL (0.31–1.44 vs 0.92–6.11 lesions; P≤0.0013) and CEL (0.10–0.46 vs 0.54–3.42 lesions; P≤0.0001) per scan across all age groups. In all age groups except the >45 to ≤55 years group, teriflunomide 14 mg significantly reduced the number of T2w lesions (0.50–0.93 vs 1.07–2.80 lesions; P≤0.001) per scan versus placebo. Similar effects on MRI lesion activity were seen with teriflunomide 7 mg versus placebo. Incidence of adverse events (AEs) generally increased with age, with no deaths reported through Year 2.

Conclusions

Over 2 years in TEMSO RMS patients, teriflunomide reduced the number of new MRI lesions versus placebo across age groups. Significant treatment effects were seen with teriflunomide 14 mg across all age groups for UCAL and CEL. Age-related increases in AEs were observed through Year 2.

STUDY SUPPORT: Sanofi.