Contributions
Abstract: P870
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: In the Phase 3 TOPIC (NCT00622700) study, teriflunomide significantly reduced risk of conversion to clinically definite MS versus placebo (primary endpoint) in patients with a first clinical episode suggestive of MS. Changes in whole brain volume may be an effective measure of neurodegeneration and correlate with disability progression and cognitive impairment in MS.
Objective: To explore the effect of teriflunomide on changes in whole brain volume in patients from the TOPIC study.
Methods: The TOPIC intent-to-treat (ITT) population included patients receiving placebo (n=197) or teriflunomide 14 mg (n=214) for ≤108 weeks. Post-hoc, blinded analysis of changes in whole brain volume were evaluated using longitudinal SIENA (Structural Image Evaluation using Normalisation of Atrophy) analysis for patients in the ITT population. Changes in whole brain volume at Months 6, 12, 18 and 24, standardized for follow-up duration, were analysed relative to baseline. Observed data are reported. A non-parametric rank ANCOVA model adjusted for covariates was used to assess treatment effects. In this post-hoc analysis, missing values were imputed and utilized for statistical modelling.
Results: At Month 24, median annualized percentage change in brain volume was -0.82 for patients receiving placebo compared with -0.47 for those receiving teriflunomide 14 mg (P< 0.0001); corresponding to a 43% reduction in brain volume loss with teriflunomide 14 mg relative to placebo. Corresponding values at months 6, 12, and 18 were -0.10/-0.01, -0.25/-0.18, and -0.49/-0.31, with reductions in whole brain volume loss of 87%, 29%, and 36% at Months 6, 12, and 18 respectively, for teriflunomide 14 mg relative to placebo (P< 0.03 for each timepoint).
Conclusions: Teriflunomide 14 mg consistently reduced percentage whole brain volume loss from baseline throughout the study. Observed reductions in brain volume loss augment the demonstrated benefit of teriflunomide in preventing relapse and disease progression in patients with a first clinical episode suggestive 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 (Claret Medical, Genzyme, Novartis, Protembis, Mapi Pharma).
MGD: Study consulting (Claret Medical); scientific advisory board (EMD Serono); institutional grant support (Novartis).
EC: Nothing to disclose.
KT: Employee of Sanofi.
SC: Employee of Sanofi with ownership interest.
NB: Nothing to disclose.
Study supported by Sanofi
Abstract: P870
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: In the Phase 3 TOPIC (NCT00622700) study, teriflunomide significantly reduced risk of conversion to clinically definite MS versus placebo (primary endpoint) in patients with a first clinical episode suggestive of MS. Changes in whole brain volume may be an effective measure of neurodegeneration and correlate with disability progression and cognitive impairment in MS.
Objective: To explore the effect of teriflunomide on changes in whole brain volume in patients from the TOPIC study.
Methods: The TOPIC intent-to-treat (ITT) population included patients receiving placebo (n=197) or teriflunomide 14 mg (n=214) for ≤108 weeks. Post-hoc, blinded analysis of changes in whole brain volume were evaluated using longitudinal SIENA (Structural Image Evaluation using Normalisation of Atrophy) analysis for patients in the ITT population. Changes in whole brain volume at Months 6, 12, 18 and 24, standardized for follow-up duration, were analysed relative to baseline. Observed data are reported. A non-parametric rank ANCOVA model adjusted for covariates was used to assess treatment effects. In this post-hoc analysis, missing values were imputed and utilized for statistical modelling.
Results: At Month 24, median annualized percentage change in brain volume was -0.82 for patients receiving placebo compared with -0.47 for those receiving teriflunomide 14 mg (P< 0.0001); corresponding to a 43% reduction in brain volume loss with teriflunomide 14 mg relative to placebo. Corresponding values at months 6, 12, and 18 were -0.10/-0.01, -0.25/-0.18, and -0.49/-0.31, with reductions in whole brain volume loss of 87%, 29%, and 36% at Months 6, 12, and 18 respectively, for teriflunomide 14 mg relative to placebo (P< 0.03 for each timepoint).
Conclusions: Teriflunomide 14 mg consistently reduced percentage whole brain volume loss from baseline throughout the study. Observed reductions in brain volume loss augment the demonstrated benefit of teriflunomide in preventing relapse and disease progression in patients with a first clinical episode suggestive 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 (Claret Medical, Genzyme, Novartis, Protembis, Mapi Pharma).
MGD: Study consulting (Claret Medical); scientific advisory board (EMD Serono); institutional grant support (Novartis).
EC: Nothing to disclose.
KT: Employee of Sanofi.
SC: Employee of Sanofi with ownership interest.
NB: Nothing to disclose.
Study supported by Sanofi