Slowing of Cortical Grey Matter Atrophy With Teriflunomide is Associated With Delayed Conversion to Clinically Definite MS
ECTRIMS Online Library. Zivadinov R. Oct 26, 2017; 200326; P671
Prof. Dr. Robert Zivadinov
Prof. Dr. Robert Zivadinov

Abstract: P671

Type: Poster

Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression

Background: 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. Teriflunomide also significantly reduced MRI activity, consistent with outcomes in patients with relapsing forms of MS in TEMSO (NCT00134563). Pathologic changes in grey matter (GM) contribute to disease worsening in MS. GM atrophy after a first clinical event is associated with conversion to CDMS and disability accumulation.
Objective: To explore the effect of cortical GM volume (CGMV) change on risk of conversion to CDMS in TOPIC.
Methods: Patients were treated with placebo (n=197), teriflunomide 7 mg (n=203) or 14 mg (n=214) for ≤108 weeks. Percentage change in CGMV was evaluated using SIENAX (Structural Image Evaluation using Normalisation of Atrophy, Cross-sectional) multi-time point analysis. Placebo and teriflunomide data at Month (M) 6, 12, 18, and 24, standardized for follow-up duration, were analysed relative to baseline. Non-parametric ANCOVA models adjusted for covariates were used to assess treatment effects at each time point separately and cumulatively. Relationship of CGMV loss to CDMS conversion over varying time of follow-up was analysed using Cox proportional hazards models adjusted for covariates.
Results: Teriflunomide 14 mg reduced median percentage CGMV change by ≥40% vs placebo at all time points (P< 0.05 at each time point; P=0.0052 for cumulative difference over 2 years). Consistent results were observed with teriflunomide 7 mg; ≥46% reduction vs placebo at all time points (P< 0.05 at M18 and M24; P=0.0089 for cumulative difference over 2 years). There was a significant association of CGMV loss with conversion to CDMS at M12 (12.4% increased risk of CDMS conversion for every 1% decrease in CGMV [P=0.0099]), and a significant treatment effect (14 mg vs placebo, risk reduction [RR]: 46.3%, P=0.0166). These significant results were replicated at M18 and M24: association of CGMV loss with CDMS conversion, 14.2%, P=0.0009 and 14.5%, P=0.0005, respectively; treatment effect, RR 42.1%, P=0.0239 and 46.6%, P=0.0093, respectively. Correlation between CGMV and CDMS will be further explored with longer-term data.
Conclusions: Consistent effects of teriflunomide on reducing CGMV loss, together with the correlation between conversion to CDMS and CGMV loss, indicate how teriflunomide may favourably impact early inflammatory and neurodegenerative components of MS.
Disclosure: RZ: Speaking and consultant fees (EMD Serono, Genzyme, Novartis); editorial board (BioMed Res Int, BMC Med, BMC Neurol, Clinical CNS Drugs, Conf Pap Neurosci, J Alzheimers Dis, Veins and Lymphatics, World J Surg Proc); financial support for research activities (Biogen Idec, Claret Medical, Genzyme, Intekrin-Coherus, Novartis, Teva Pharmaceuticals).
MGD: Study consulting (Claret Medical); scientific advisory board (EMD Serono); institutional grant support (Novartis).
EC: Nothing to disclose.
KT: Employee of Sanofi Genzyme.
SC: Employee of Sanofi Genzyme with ownership interest.
NB: Nothing to disclose.
Study supported by Sanofi Genzyme.

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