Contributions
Abstract: P685
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: In TEMSO (NCT00134563) and TOWER (NCT00751881), teriflunomide 14 mg significantly reduced the risk of disability worsening vs placebo (PBO). In a post hoc, blinded SIENA (Structural Image Evaluation using Normalization of Atrophy) analysis of the TEMSO MRI dataset, teriflunomide significantly reduced brain volume loss (BVL) vs PBO. Further analysis indicated a strong correlation between BVL and disability worsening over 2 years in TEMSO; patients with lower rates of BVL had better disability outcomes. Studies in MS also show correlation between BVL and cognitive impairment, as measured using the Paced Auditory Serial Addition Test (PASAT).
Objective: To explore the relationship between BVL and long-term changes in PASAT-3 scores in TEMSO and its extension.
Methods: The effect of teriflunomide on cognitive function was assessed by change from baseline (BL) in PASAT-3 scores, 1 of 3 components of the Multiple Sclerosis Functional Composite, a predefined outcome in the TEMSO core (N=1086) and extension (NCT00803049; N=740) studies. Additional analyses assessed change in PASAT-3 scores over 5 years by categorizing percentage brain volume changes from BL to Year 2 (assessed by SIENA) into groups of varying degree of BVL change.
Results: Adjusted mean changes from BL to Week 96 in PASAT-3 Z-score were -0.022 and 0.073 for PBO and teriflunomide 14-mg groups, respectively (positive score indicated an improvement); P=0.0435 for difference vs PBO. Improvements in PASAT-3 Z-score with teriflunomide 14 mg were observed over the long term: mean (SD) changes from BL at Weeks 156 and 276 were 0.194 (0.634) and 0.200 (0.677), respectively. In terms of raw PASAT-3 score for patients treated with teriflunomide 14 mg, the mean (SD) changes from BL at Weeks 96, 156, and 276 were 1.17 (5.90), 2.36 (7.73), and 2.43 (8.24) units of change, respectively.
In an association analysis, the group with the least BVL from BL to Year 2 demonstrated a significant improvement in PASAT-3 score with teriflunomide treatment over 5 years vs the group with the most BVL.
Conclusions: Teriflunomide significantly slowed the rate of cognitive decline, vs PBO, over 2 years in the TEMSO core study. This effect was maintained over the extension study, demonstrating the positive effect of long-term teriflunomide treatment on slowing cognitive decline, with the greatest effect observed in patients with the least BVL. This study highlights the long-term predictive value of BVL earlier in the disease course.
Disclosure: Study supported by Sanofi Genzyme.
TS: Author´s current and previous institutions have received compensation for author serving on scientific advisory boards/consultation and speaking (Actelion, ATI, Biogen, Desitin, Electrocore, Novartis, Sanofi Genzyme, Teva); research support (Novartis Pharmaceuticals Switzerland, Swiss MS Society, Swiss National Science Foundation).
MPS: Consulting fees (Biogen, Genzyme, Merck Serono, Novartis, Roche, Synthon, Teva).
JSW: Author has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria (AbbVie, Academic CME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, Medday Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals, WebMD); royalties received for out licensed monoclonal antibodies (through UTHealth, Houston, TX, from Millipore Corporation).
JW: CEO of Medical Image Analysis Center (MIAC AG), Basel, Switzerland; speaker honoraria (Bayer, Biogen, Novartis, Teva); advisory boards and research grants (Biogen, Novartis, Roche, Sanofi Genzyme); supported by the German Ministry of Science (BMBF/KKNMS) and German Ministry of Economy (BMWi) and EU (Horizon 2020).
KT and MM: Employees of Sanofi Genzyme.
SC: Employee of Sanofi Genzyme, with ownership interest.
LK: Author´s institution (University Hospital Basel) has received in last 3 years and used exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, XenoPort); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, Teva); support of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva); license fees for Neurostatus products; grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, Swiss National Research Foundation).
Abstract: P685
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: In TEMSO (NCT00134563) and TOWER (NCT00751881), teriflunomide 14 mg significantly reduced the risk of disability worsening vs placebo (PBO). In a post hoc, blinded SIENA (Structural Image Evaluation using Normalization of Atrophy) analysis of the TEMSO MRI dataset, teriflunomide significantly reduced brain volume loss (BVL) vs PBO. Further analysis indicated a strong correlation between BVL and disability worsening over 2 years in TEMSO; patients with lower rates of BVL had better disability outcomes. Studies in MS also show correlation between BVL and cognitive impairment, as measured using the Paced Auditory Serial Addition Test (PASAT).
Objective: To explore the relationship between BVL and long-term changes in PASAT-3 scores in TEMSO and its extension.
Methods: The effect of teriflunomide on cognitive function was assessed by change from baseline (BL) in PASAT-3 scores, 1 of 3 components of the Multiple Sclerosis Functional Composite, a predefined outcome in the TEMSO core (N=1086) and extension (NCT00803049; N=740) studies. Additional analyses assessed change in PASAT-3 scores over 5 years by categorizing percentage brain volume changes from BL to Year 2 (assessed by SIENA) into groups of varying degree of BVL change.
Results: Adjusted mean changes from BL to Week 96 in PASAT-3 Z-score were -0.022 and 0.073 for PBO and teriflunomide 14-mg groups, respectively (positive score indicated an improvement); P=0.0435 for difference vs PBO. Improvements in PASAT-3 Z-score with teriflunomide 14 mg were observed over the long term: mean (SD) changes from BL at Weeks 156 and 276 were 0.194 (0.634) and 0.200 (0.677), respectively. In terms of raw PASAT-3 score for patients treated with teriflunomide 14 mg, the mean (SD) changes from BL at Weeks 96, 156, and 276 were 1.17 (5.90), 2.36 (7.73), and 2.43 (8.24) units of change, respectively.
In an association analysis, the group with the least BVL from BL to Year 2 demonstrated a significant improvement in PASAT-3 score with teriflunomide treatment over 5 years vs the group with the most BVL.
Conclusions: Teriflunomide significantly slowed the rate of cognitive decline, vs PBO, over 2 years in the TEMSO core study. This effect was maintained over the extension study, demonstrating the positive effect of long-term teriflunomide treatment on slowing cognitive decline, with the greatest effect observed in patients with the least BVL. This study highlights the long-term predictive value of BVL earlier in the disease course.
Disclosure: Study supported by Sanofi Genzyme.
TS: Author´s current and previous institutions have received compensation for author serving on scientific advisory boards/consultation and speaking (Actelion, ATI, Biogen, Desitin, Electrocore, Novartis, Sanofi Genzyme, Teva); research support (Novartis Pharmaceuticals Switzerland, Swiss MS Society, Swiss National Science Foundation).
MPS: Consulting fees (Biogen, Genzyme, Merck Serono, Novartis, Roche, Synthon, Teva).
JSW: Author has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria (AbbVie, Academic CME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, Medday Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals, WebMD); royalties received for out licensed monoclonal antibodies (through UTHealth, Houston, TX, from Millipore Corporation).
JW: CEO of Medical Image Analysis Center (MIAC AG), Basel, Switzerland; speaker honoraria (Bayer, Biogen, Novartis, Teva); advisory boards and research grants (Biogen, Novartis, Roche, Sanofi Genzyme); supported by the German Ministry of Science (BMBF/KKNMS) and German Ministry of Economy (BMWi) and EU (Horizon 2020).
KT and MM: Employees of Sanofi Genzyme.
SC: Employee of Sanofi Genzyme, with ownership interest.
LK: Author´s institution (University Hospital Basel) has received in last 3 years and used exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, XenoPort); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, Teva); support of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva); license fees for Neurostatus products; grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, Swiss National Research Foundation).