Contributions
Abstract: P903
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing forms of MS. Analysis of the fingolimod FREEDOMS studies investigated if fingolimod's effect on percent brain volume change (PBVC) is mediated exclusively via its effects on focal damage or if it also acts independently by reducing diffuse damage. It was found that 54% of fingolimod's effect on PBVC is independent of its effects on visible focal damage. This analysis was replicated using data from teriflunomide-treated patients.
Objective: To evaluate teriflunomide's effect on diffuse brain tissue damage independent of its effect on focal inflammatory disease activity in post hoc analyses of the Phase 3 TEMSO study.
Methods: In TEMSO, patients were randomised 1:1:1 to placebo, teriflunomide 7mg or 14mg for ≤108 weeks. Structural Image Evaluation using Normalisation of Atrophy (SIENA) assessed PBVC at years 1 and 2. To evaluate the independent effect of teriflunomide on PBVC, two regression analyses were done in patients with complete MRI data, as in De Stefano (2016). An unadjusted model evaluated the effect of treatment (teriflunomide 14mg vs placebo) on PBVC, then an adjusted model, adding active lesions (contrast enhancing T1w lesions and/or new/enlarging T2w lesions; yes/no) and relapses (yes/no), was compared to the unadjusted model. The relative difference between models represents the treatment effect on PBVC independent of the effect on active lesions and relapses.
Results: Statistically significant treatment effects of teriflunomide on PBVC were observed at years 1 and 2. At year 2, in the unadjusted model, mean PBVC (95% CI) was -1.55% (−1.77, −1.32) in the placebo group and −1.06% (−1.24, −0.88) in the 14mg group; the estimated treatment effect was 0.49% (P=0.0004). In the adjusted model, mean PBVC was −1.30% (−1.51, −1.09) in the placebo group and −1.01% (−1.21, −0.81) in the 14mg group and the estimated treatment effect was 0.30% (P=0.0207). The treatment effect of teriflunomide 14mg on PBVC independent of its effects on focal damage (relative difference between models) was 61%. Similar results were observed at year 1 and in the ITT population.
Conclusions: Significant BVL treatment effects of teriflunomide 14mg were observed compared to placebo; most of which were independent of its effect on focal lesions and relapses, thus the effect on BVL may be due to reducing diffuse neurodegeneration rather than secondary to ameliorated focal inflammation.
Disclosure: TS: Author's current and previous institutions have received compensation for author serving on scientific advisory boards/consultation and speaking from Actelion, ATI, Biogen, Desitin, Electrocore, Novartis, Sanofi, Genzyme, and Teva; research support from Novartis, Swiss MS Society, and Swiss National Science Foundation. GC: Compensation for consulting services and/or speaking activities from Almirall, Biogen, Celgene, Excemed, Forward Pharma, Genzyme, Merck, Novartis, Receptos, Roche, Sanofi, and Teva; fees for non-CME services from Almirall, Bayer, Biogen, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, SSIF, and Teva. CLF: Consulting fees, honoraria, or scientific committee support from Biogen, Genzyme, MedDay, Merck Serono, Novartis, Roche, and Teva. MP: Consulting fees, honoraria, or scientific committee support from Bayer, Genzyme, Merck Serono, and Novartis. DC: Speaker honoraria from Bayer and Glaxo, compensation on Scientific Advisory Board from Roche and Merck Serono, educational support from Genzyme, Stendhal, Roche, Bayer, Asofarma, Merck Serono and Novartis. JL: Consulting fees, honoraria and grant funding from Acorda, Biogen, Genentech, Genzyme, Novartis and Teva. LK: Ludwig Kappos' Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, Sanofi-Aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations. EWR: Speaker honoraria and travel compensation from Bayer, Biogen, Fondazione Italiana Sclerosi Multipla, Genzyme, Novartis, Merck-Serono, MorphoSys, and Synthon; consultancy fees from Bayer, Biogen, Fondazione Italiana Sclerosi Multipla, Genzyme, Novartis, Merck-Serono, Synthon, MorphoSys; institutional research support from Novartis, Biogen, Actelion, Basilea, SAKK, and Synarc. AL: Employee of Sanofi with ownership interest. SC: Employee of Sanofi, with ownership interest. KT: Employee of Sanofi with ownership interest. JW: CEO of the MIAC AG in Basel, Switzerland and is on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche.
Study supported by Sanofi.
Abstract: P903
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing forms of MS. Analysis of the fingolimod FREEDOMS studies investigated if fingolimod's effect on percent brain volume change (PBVC) is mediated exclusively via its effects on focal damage or if it also acts independently by reducing diffuse damage. It was found that 54% of fingolimod's effect on PBVC is independent of its effects on visible focal damage. This analysis was replicated using data from teriflunomide-treated patients.
Objective: To evaluate teriflunomide's effect on diffuse brain tissue damage independent of its effect on focal inflammatory disease activity in post hoc analyses of the Phase 3 TEMSO study.
Methods: In TEMSO, patients were randomised 1:1:1 to placebo, teriflunomide 7mg or 14mg for ≤108 weeks. Structural Image Evaluation using Normalisation of Atrophy (SIENA) assessed PBVC at years 1 and 2. To evaluate the independent effect of teriflunomide on PBVC, two regression analyses were done in patients with complete MRI data, as in De Stefano (2016). An unadjusted model evaluated the effect of treatment (teriflunomide 14mg vs placebo) on PBVC, then an adjusted model, adding active lesions (contrast enhancing T1w lesions and/or new/enlarging T2w lesions; yes/no) and relapses (yes/no), was compared to the unadjusted model. The relative difference between models represents the treatment effect on PBVC independent of the effect on active lesions and relapses.
Results: Statistically significant treatment effects of teriflunomide on PBVC were observed at years 1 and 2. At year 2, in the unadjusted model, mean PBVC (95% CI) was -1.55% (−1.77, −1.32) in the placebo group and −1.06% (−1.24, −0.88) in the 14mg group; the estimated treatment effect was 0.49% (P=0.0004). In the adjusted model, mean PBVC was −1.30% (−1.51, −1.09) in the placebo group and −1.01% (−1.21, −0.81) in the 14mg group and the estimated treatment effect was 0.30% (P=0.0207). The treatment effect of teriflunomide 14mg on PBVC independent of its effects on focal damage (relative difference between models) was 61%. Similar results were observed at year 1 and in the ITT population.
Conclusions: Significant BVL treatment effects of teriflunomide 14mg were observed compared to placebo; most of which were independent of its effect on focal lesions and relapses, thus the effect on BVL may be due to reducing diffuse neurodegeneration rather than secondary to ameliorated focal inflammation.
Disclosure: TS: Author's current and previous institutions have received compensation for author serving on scientific advisory boards/consultation and speaking from Actelion, ATI, Biogen, Desitin, Electrocore, Novartis, Sanofi, Genzyme, and Teva; research support from Novartis, Swiss MS Society, and Swiss National Science Foundation. GC: Compensation for consulting services and/or speaking activities from Almirall, Biogen, Celgene, Excemed, Forward Pharma, Genzyme, Merck, Novartis, Receptos, Roche, Sanofi, and Teva; fees for non-CME services from Almirall, Bayer, Biogen, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, SSIF, and Teva. CLF: Consulting fees, honoraria, or scientific committee support from Biogen, Genzyme, MedDay, Merck Serono, Novartis, Roche, and Teva. MP: Consulting fees, honoraria, or scientific committee support from Bayer, Genzyme, Merck Serono, and Novartis. DC: Speaker honoraria from Bayer and Glaxo, compensation on Scientific Advisory Board from Roche and Merck Serono, educational support from Genzyme, Stendhal, Roche, Bayer, Asofarma, Merck Serono and Novartis. JL: Consulting fees, honoraria and grant funding from Acorda, Biogen, Genentech, Genzyme, Novartis and Teva. LK: Ludwig Kappos' Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, Sanofi-Aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations. EWR: Speaker honoraria and travel compensation from Bayer, Biogen, Fondazione Italiana Sclerosi Multipla, Genzyme, Novartis, Merck-Serono, MorphoSys, and Synthon; consultancy fees from Bayer, Biogen, Fondazione Italiana Sclerosi Multipla, Genzyme, Novartis, Merck-Serono, Synthon, MorphoSys; institutional research support from Novartis, Biogen, Actelion, Basilea, SAKK, and Synarc. AL: Employee of Sanofi with ownership interest. SC: Employee of Sanofi, with ownership interest. KT: Employee of Sanofi with ownership interest. JW: CEO of the MIAC AG in Basel, Switzerland and is on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche.
Study supported by Sanofi.