Contributions
Abstract: P734
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting MS. In both TEMSO (NCT00134563) and TOWER (NCT00751881), teriflunomide 14 mg significantly slowed disability worsening vs placebo, and was highly correlated with the significant effects of teriflunomide in reducing brain volume loss (BVL) observed in a SIENA (structural image evaluation using normalization of atrophy) analysis of TEMSO (no MRI analysis was performed in TOWER). In subgroup post hoc analyses of TEMSO and TOWER, teriflunomide 14 mg had positive effects on annualized relapse rate and disability worsening in both treatment-naïve patients and those previously exposed to disease-modifying therapy (DMT).
Objectives: To report effects of teriflunomide on BVL according to prior DMT exposure in a subgroup analysis of TEMSO.
Methods: Blinded SIENA analysis was conducted on patient scans from TEMSO (n=969) to determine BVL in Year 1 (n=808) and Year 2 (n=709). Post hoc analyses were performed according to prior DMT status in the 2 years before study entry. Between-group comparisons were made using rank ANCOVA.
Results: At baseline, normalized brain volume was lower in the prior-treated vs treatment-naïve group. Teriflunomide 14 mg significantly reduced BVL vs placebo in both groups, with a greater effect in prior-treated patients. In treatment-naïve patients, median percentage BVL from baseline to Year 1 was -0.40 for teriflunomide 14 mg (n=189) and -0.57 for placebo (n=209); relative change, 30% (P=0.0025); this effect was also observed from baseline to Year 2: teriflunomide 14 mg, -0.93 (n=177); placebo, ‑1.12 (n=182); relative change, 17% (P=0.0109). In prior-treated patients, median percentage BVL from baseline to Year 1 was -0.31 (n=74) and -0.67 (n=67) for 14 mg and placebo, respectively (relative change, 53%; P=0.0119); corresponding changes at Year 2 were -0.73 (n=58) and -1.51 (n=52); relative change, 51% (P=0.0019). Effect sizes were maintained when the prior-treated group was further stratified by number of DMTs received.
Conclusions: These data support the beneficial effects of teriflunomide on slowing BVL in both prior-treated and treatment-naïve patients, vs placebo. Although prior-treated patients already had significant BVL compared with treatment-naïve patients at baseline, teriflunomide 14 mg was associated with a more profound effect on slowing BVL in prior-treated patients, consistent with previously reported positive clinical and MRI outcomes.
Disclosure: Study supported by Sanofi Genzyme.
MSF: Research/educational grant support (Bayer HealthCare, Genzyme); honoraria/consulting fees (Bayer HealthCare, Biogen Idec, EMD Canada, Novartis, Sanofi, Teva Canada Innovation); member of company advisory boards/board of directors/other similar group (Bayer HealthCare, Biogen Idec, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, Teva Canada Innovation).
TS: Author´s previous and current institution have received payments for research for consulting and speaking activities (Actelion, Biogen Idec, ElectroCore, Genzyme, Mitsubishi Pharma, Novartis); grants received (EFIC-Grünenthal, Novartis Pharmaceuticals Switzerland, Swiss MS Society, Swiss National Research Foundation).
E-WR: Author"s institution, MIAC AG, has received payments used exclusively for research (Actelion, Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Sanofi).
JW: CEO of MIAC AG Basel, Switzerland; speaker honoraria (Bayer, Biogen, Novartis, Teva); advisory boards and research grants (Biogen, Novartis); supported by the German Ministry of Science (BMBF/KKNMS) and German Ministry of Economy (BMWi).
AEM: Consulting fees (Accordant Health Services, Acorda Therapeutics, Alkermes, Biogen Idec, EMD Serono, Genentech, Genzyme, GSK, Mallinckrodt Pharmaceuticals [Questcor], Novartis, Roche, Teva); contracted research (Biogen Idec, Genentech, Novartis, Questcor, Roche, Sanofi).
KT: Employee of Sanofi Genzyme.
MAP: Employee of Sanofi Genzyme.
SC: Employee of Sanofi Genzyme, with ownership interests.
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); royalties (Neurostatus Systems GmbH); grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, Swiss National Research Foundation.
Abstract: P734
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting MS. In both TEMSO (NCT00134563) and TOWER (NCT00751881), teriflunomide 14 mg significantly slowed disability worsening vs placebo, and was highly correlated with the significant effects of teriflunomide in reducing brain volume loss (BVL) observed in a SIENA (structural image evaluation using normalization of atrophy) analysis of TEMSO (no MRI analysis was performed in TOWER). In subgroup post hoc analyses of TEMSO and TOWER, teriflunomide 14 mg had positive effects on annualized relapse rate and disability worsening in both treatment-naïve patients and those previously exposed to disease-modifying therapy (DMT).
Objectives: To report effects of teriflunomide on BVL according to prior DMT exposure in a subgroup analysis of TEMSO.
Methods: Blinded SIENA analysis was conducted on patient scans from TEMSO (n=969) to determine BVL in Year 1 (n=808) and Year 2 (n=709). Post hoc analyses were performed according to prior DMT status in the 2 years before study entry. Between-group comparisons were made using rank ANCOVA.
Results: At baseline, normalized brain volume was lower in the prior-treated vs treatment-naïve group. Teriflunomide 14 mg significantly reduced BVL vs placebo in both groups, with a greater effect in prior-treated patients. In treatment-naïve patients, median percentage BVL from baseline to Year 1 was -0.40 for teriflunomide 14 mg (n=189) and -0.57 for placebo (n=209); relative change, 30% (P=0.0025); this effect was also observed from baseline to Year 2: teriflunomide 14 mg, -0.93 (n=177); placebo, ‑1.12 (n=182); relative change, 17% (P=0.0109). In prior-treated patients, median percentage BVL from baseline to Year 1 was -0.31 (n=74) and -0.67 (n=67) for 14 mg and placebo, respectively (relative change, 53%; P=0.0119); corresponding changes at Year 2 were -0.73 (n=58) and -1.51 (n=52); relative change, 51% (P=0.0019). Effect sizes were maintained when the prior-treated group was further stratified by number of DMTs received.
Conclusions: These data support the beneficial effects of teriflunomide on slowing BVL in both prior-treated and treatment-naïve patients, vs placebo. Although prior-treated patients already had significant BVL compared with treatment-naïve patients at baseline, teriflunomide 14 mg was associated with a more profound effect on slowing BVL in prior-treated patients, consistent with previously reported positive clinical and MRI outcomes.
Disclosure: Study supported by Sanofi Genzyme.
MSF: Research/educational grant support (Bayer HealthCare, Genzyme); honoraria/consulting fees (Bayer HealthCare, Biogen Idec, EMD Canada, Novartis, Sanofi, Teva Canada Innovation); member of company advisory boards/board of directors/other similar group (Bayer HealthCare, Biogen Idec, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, Teva Canada Innovation).
TS: Author´s previous and current institution have received payments for research for consulting and speaking activities (Actelion, Biogen Idec, ElectroCore, Genzyme, Mitsubishi Pharma, Novartis); grants received (EFIC-Grünenthal, Novartis Pharmaceuticals Switzerland, Swiss MS Society, Swiss National Research Foundation).
E-WR: Author"s institution, MIAC AG, has received payments used exclusively for research (Actelion, Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Sanofi).
JW: CEO of MIAC AG Basel, Switzerland; speaker honoraria (Bayer, Biogen, Novartis, Teva); advisory boards and research grants (Biogen, Novartis); supported by the German Ministry of Science (BMBF/KKNMS) and German Ministry of Economy (BMWi).
AEM: Consulting fees (Accordant Health Services, Acorda Therapeutics, Alkermes, Biogen Idec, EMD Serono, Genentech, Genzyme, GSK, Mallinckrodt Pharmaceuticals [Questcor], Novartis, Roche, Teva); contracted research (Biogen Idec, Genentech, Novartis, Questcor, Roche, Sanofi).
KT: Employee of Sanofi Genzyme.
MAP: Employee of Sanofi Genzyme.
SC: Employee of Sanofi Genzyme, with ownership interests.
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); royalties (Neurostatus Systems GmbH); grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, Swiss National Research Foundation.