Effect of Teriflunomide on Cortical Atrophy in a Subgroup Analysis of Patients Presenting with Optic Neuritis in the Phase 3 TOPIC Study

Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting MS. In TOPIC (NCT00622700), teriflunomide significantly reduced risk of conversion to clinically definite MS (CDMS) vs placebo in patients with a first clinical episode suggestive of MS, including in patients with a primary presentation of optic neuritis (ON). Teriflunomide also significantly reduced MRI activity vs placebo, consistent with outcomes in patients with relapsing forms of MS in TEMSO (NCT00134563). Pathologic changes in gray matter (GM) are a hallmark of disease worsening in MS. GM atrophy after a first clinical event is associated with conversion to CDMS and disability accumulation.

Objectives: To describe effects of teriflunomide on cortical gray matter volume (CGMV) change in patients with a first clinical episode suggestive of MS, and in a subgroup of patients with ON at baseline in TOPIC.

Methods: Patients were treated with placebo (n=197), teriflunomide 7 mg (n=203), or 14 mg (n=214) for ≤108 weeks. Post hoc analyses were performed in a subgroup of patients defined by a primary presentation of ON. Of 614 patients, 200 (32.6%) had ON (placebo, n=57; 7 mg, n=76; 14 mg, n=67) at baseline. Percentage change in CGMV was evaluated using SIENAX multi-timepoint analysis, which directly calculates volumetric changes from longitudinal data. Data from Months 6, 12, 18, and 24, standardized for follow-up duration, were analyzed relative to baseline. Treatment group comparisons were made using rank ANCOVA.

Results: In the overall TOPIC population (N=614), teriflunomide reduced the median percentage CGMV change vs placebo (teriflunomide 7 mg/14 mg relative reduction vs placebo at: Month 6, 58.2/119.2% [P=0.071/P=0.017]; Month 12, 79.8/61.4% [P=0.041/P=0.029]; Month 18, 69.5/66.8% [P=0.006/P=0.003]; and Month 24, 46.0/40.2% [P=0.007/P=0.039]).

Median percentage CGMV change from baseline was lower with teriflunomide 14 mg vs placebo in patients with ON (teriflunomide 7 mg/14 mg relative reduction vs placebo at: Month 6, 78.8/89.8% [P=0.078/P=0.076]; Month 12, 98.1/65.8% [P=0.146/P=0.185]; Month 18, 92.8/50.1%; and Month 24, 94.3/31.9% [P=0.01/P=0.278]).

Conclusions: Consistent with the reduced risk of conversion to CDMS, teriflunomide demonstrated a positive effect on slowing CGMV loss across all time points over 2 years in TOPIC, including in a subgroup of patients with baseline ON. These results indicate that teriflunomide may have a favorable impact on the early neurodegenerative component of MS.