Contributions
Abstract: P1140
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Teriflunomide (Aubagio®) has been shown to reduce brain atrophy progression, compared to placebo over 2 years. Most recently, it was demonstrated that MS patients treated with teriflunomide over 12 months showed similar volume changes in gray matter (GM), compared to age- and sex-matched healthy controls (HCs). We hypothesized that the effect of teriflunomide on GM pathology may be related to the change in humoral response to Espstein-Barr virus (EBV).
Objective: This study aimed to explore whether the effect of teriflunomide on GM volume loss in relapsing MS patients over 12 months is associated with the change in humoral response to EBV.
Methods: This was a prospective, observational, single-blinded, longitudinal study of 30 relapsing MS patients, who started de-novo treatment with teriflunomide, and 20 age- and sex-matched HCs. Subjects were assessed at baseline, 6 and 12 months with clinical, MRI and EBV examinations. MRI outcomes included percent change from baseline to 6, 6 to 12 and baseline to 12 months in whole brain volume using SIENA, in cortical volumes using the SIENAX multi-time point algorithm, and in deep GM volumes using the FIRST methods. Serum samples were analysed for IgG antibodies against EBV viral capsid antigen (VCA) and nuclear antigen-1 (EBNA-1) and their quartiles were determined on whole study sample.
Results: At baseline, MS subjects with the highest quartile of anti-EBV VCA showed significantly decreased caudate (p=0.002) and total deep GM (p=0.027) volumes and increased T1 lesion volume (LV) (p=0.014). The median decrease in EBV titre over the follow-up, after teriflunomide initiation, was 5.3% in MS patients, while no changes were observed in HCs. In correlation analysis, MS patients who showed the highest decrease in EBV VCA titre from baseline to follow-up, developed less GM and cortical atrophy (p< 0.05). MS patients who showed the highest decrease in EBV EBNA-1 titre from baseline to follow-up, developed less hippocampal atrophy (p< 0.05). Over the 12-month follow-up, the percent change in whole brain was -0.38% in HCs and -0.50% in MS patients, p=0.378. The percentage change in cortical volume was -0.31% in HC vs. -0.80% in MS, p=0.302.
Conclusions: These findings suggest that the effect of teriflunomide on slowing down whole brain and GM atrophy may be mediated by its effect on altering humoral response to EBV.
Disclosure:
Robert Zivadinov received personal compensation from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi, Claret Medical, IMS Health and Novartis for speaking and consultant fees. He received financial support for research activities from Teva Pharmaceuticals, Genzyme-Sanofi, Novartis, Claret Medical, Intekrin and IMS Health.
Channa Kolb has received speaker honoraria from Novartis, Genzyme and Biogen-Idec.
Noopur Modi, Jill Carl, Jesper Hagemier, Niels Bergsland, Deepa Ramasamy, Jacqueline Durfee have nothing to disclose.
Bianca Weinstock- Guttman has participated in speaker´s bureaus and served as a consultant for Biogen Idec, Teva Neuroscience, EMD Serono, Novartis, Genzyme & Sanofi, Mylan Inc., and Acorda Therapeutics, Inc. Dr. Weinstock-Guttman also has received grant/research support from the agencies listed in the previous sentence as well as Questcor Pharmaceuticals, Inc., and Shire. She serves in the editorial board for BMC Neurology, Journal of International MS, Journal of Multiple Sclerosis.
Murali Ramanathan is on the editorial board for AAPS Journal, receives publishing royalties from Pinnacle, Summit and Zenith, received research support from Serono, Novartis, Pfizer, Biogen, Department of Defense, National Multiple Sclerosis Society
Abstract: P1140
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Teriflunomide (Aubagio®) has been shown to reduce brain atrophy progression, compared to placebo over 2 years. Most recently, it was demonstrated that MS patients treated with teriflunomide over 12 months showed similar volume changes in gray matter (GM), compared to age- and sex-matched healthy controls (HCs). We hypothesized that the effect of teriflunomide on GM pathology may be related to the change in humoral response to Espstein-Barr virus (EBV).
Objective: This study aimed to explore whether the effect of teriflunomide on GM volume loss in relapsing MS patients over 12 months is associated with the change in humoral response to EBV.
Methods: This was a prospective, observational, single-blinded, longitudinal study of 30 relapsing MS patients, who started de-novo treatment with teriflunomide, and 20 age- and sex-matched HCs. Subjects were assessed at baseline, 6 and 12 months with clinical, MRI and EBV examinations. MRI outcomes included percent change from baseline to 6, 6 to 12 and baseline to 12 months in whole brain volume using SIENA, in cortical volumes using the SIENAX multi-time point algorithm, and in deep GM volumes using the FIRST methods. Serum samples were analysed for IgG antibodies against EBV viral capsid antigen (VCA) and nuclear antigen-1 (EBNA-1) and their quartiles were determined on whole study sample.
Results: At baseline, MS subjects with the highest quartile of anti-EBV VCA showed significantly decreased caudate (p=0.002) and total deep GM (p=0.027) volumes and increased T1 lesion volume (LV) (p=0.014). The median decrease in EBV titre over the follow-up, after teriflunomide initiation, was 5.3% in MS patients, while no changes were observed in HCs. In correlation analysis, MS patients who showed the highest decrease in EBV VCA titre from baseline to follow-up, developed less GM and cortical atrophy (p< 0.05). MS patients who showed the highest decrease in EBV EBNA-1 titre from baseline to follow-up, developed less hippocampal atrophy (p< 0.05). Over the 12-month follow-up, the percent change in whole brain was -0.38% in HCs and -0.50% in MS patients, p=0.378. The percentage change in cortical volume was -0.31% in HC vs. -0.80% in MS, p=0.302.
Conclusions: These findings suggest that the effect of teriflunomide on slowing down whole brain and GM atrophy may be mediated by its effect on altering humoral response to EBV.
Disclosure:
Robert Zivadinov received personal compensation from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi, Claret Medical, IMS Health and Novartis for speaking and consultant fees. He received financial support for research activities from Teva Pharmaceuticals, Genzyme-Sanofi, Novartis, Claret Medical, Intekrin and IMS Health.
Channa Kolb has received speaker honoraria from Novartis, Genzyme and Biogen-Idec.
Noopur Modi, Jill Carl, Jesper Hagemier, Niels Bergsland, Deepa Ramasamy, Jacqueline Durfee have nothing to disclose.
Bianca Weinstock- Guttman has participated in speaker´s bureaus and served as a consultant for Biogen Idec, Teva Neuroscience, EMD Serono, Novartis, Genzyme & Sanofi, Mylan Inc., and Acorda Therapeutics, Inc. Dr. Weinstock-Guttman also has received grant/research support from the agencies listed in the previous sentence as well as Questcor Pharmaceuticals, Inc., and Shire. She serves in the editorial board for BMC Neurology, Journal of International MS, Journal of Multiple Sclerosis.
Murali Ramanathan is on the editorial board for AAPS Journal, receives publishing royalties from Pinnacle, Summit and Zenith, received research support from Serono, Novartis, Pfizer, Biogen, Department of Defense, National Multiple Sclerosis Society