Contributions
Abstract: P733
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: Teriflunomide is a once-daily oral immunomodulator for relapsing-remitting MS. In 2 phase 3 studies, teriflunomide 14 mg significantly reduced risk of disability worsening vs placebo. This is consistent with significant effects of teriflunomide vs placebo on reducing brain volume loss (BVL) observed in a post hoc, blinded SIENA (structural image evaluation using normalization of atrophy) analysis of TEMSO magnetic resonance imaging scans. Further analysis of these data provided evidence of a strong correlation between BVL and disability worsening, and also showed that teriflunomide significantly slowed BVL vs placebo independent of disability worsening over the course of the 2‑year study.
Objective(s): To explore the association of BVL and long-term disability worsening in an analysis of TEMSO (NCT00134563) and its long-term extension (NCT00803049).
Methods: SIENA analysis was conducted on patient scans from TEMSO (n=969) to determine BVL in the first (n=808) and second (n=709) year of the study. Additional analyses were conducted on the total population (regardless of treatment allocation) by categorizing percentage brain volume changes (PBVC) from baseline to Year 2 into quartiles (Q1-Q4) and evaluating the probability of 12- and 24-week confirmed disability worsening over 5 years in the TEMSO extension. Probability of worsening was derived from Kaplan-Meier estimates and was compared between quartiles using a Cox proportional hazards model with PBVC categories, Expanded Disability Status Scale strata at baseline, and region as covariates.
Results: The group with the most marked BVL from baseline to Year 2 (ie, Q1; n=177) had a significantly higher risk of both 12- and 24-week confirmed disability worsening after 5 years than those in the quartile with the lowest BVL (Q4; n=178). Thus, in Q1, probability of 12-week confirmed disability worsening at 5 years was 0.487 (95% confidence interval [CI] 0.410, 0.569) vs 0.315 (95% CI 0.251, 0.391) in Q4 (hazard ratio [HR] for Q1 vs Q4: 0.611 [95% CI 0.432, 0.865]; P=0.0055). Similarly, probability of 24-week confirmed disability worsening at 5 years was significantly higher in Q1 vs Q4 (HR: 0.566 [95% CI 0.386, 0.830]; P=0.0036).
Conclusions: These analyses provide further evidence of the association between BVL and later disability worsening. Greater rates of BVL over 2 years are predictive of longer term disability worsening at 5 years in the TEMSO extension.
Disclosure: Study supported by Sanofi Genzyme.
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.
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).
KT: Employee of Sanofi Genzyme.
MAP: Employee of Sanofi Genzyme.
SC: Employee of Sanofi Genzyme, with ownership interests.
JSW: Within the last 3 years, consulting agreements (AbbVie, Actelion, Alkermes, Athersys, Inc., Bayer HeathCare, EMD Serono, Forward Pharma, Genzyme, Novartis, Roche, Taketa, Teva, XenoPort); contracted research (Genzyme, National Institutes of Health, National MS Society); royalties (for monoclonal antibodies out-licensed to Chemicon International), through the University of Texas Health Science Center at Houston.
Abstract: P733
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: Teriflunomide is a once-daily oral immunomodulator for relapsing-remitting MS. In 2 phase 3 studies, teriflunomide 14 mg significantly reduced risk of disability worsening vs placebo. This is consistent with significant effects of teriflunomide vs placebo on reducing brain volume loss (BVL) observed in a post hoc, blinded SIENA (structural image evaluation using normalization of atrophy) analysis of TEMSO magnetic resonance imaging scans. Further analysis of these data provided evidence of a strong correlation between BVL and disability worsening, and also showed that teriflunomide significantly slowed BVL vs placebo independent of disability worsening over the course of the 2‑year study.
Objective(s): To explore the association of BVL and long-term disability worsening in an analysis of TEMSO (NCT00134563) and its long-term extension (NCT00803049).
Methods: SIENA analysis was conducted on patient scans from TEMSO (n=969) to determine BVL in the first (n=808) and second (n=709) year of the study. Additional analyses were conducted on the total population (regardless of treatment allocation) by categorizing percentage brain volume changes (PBVC) from baseline to Year 2 into quartiles (Q1-Q4) and evaluating the probability of 12- and 24-week confirmed disability worsening over 5 years in the TEMSO extension. Probability of worsening was derived from Kaplan-Meier estimates and was compared between quartiles using a Cox proportional hazards model with PBVC categories, Expanded Disability Status Scale strata at baseline, and region as covariates.
Results: The group with the most marked BVL from baseline to Year 2 (ie, Q1; n=177) had a significantly higher risk of both 12- and 24-week confirmed disability worsening after 5 years than those in the quartile with the lowest BVL (Q4; n=178). Thus, in Q1, probability of 12-week confirmed disability worsening at 5 years was 0.487 (95% confidence interval [CI] 0.410, 0.569) vs 0.315 (95% CI 0.251, 0.391) in Q4 (hazard ratio [HR] for Q1 vs Q4: 0.611 [95% CI 0.432, 0.865]; P=0.0055). Similarly, probability of 24-week confirmed disability worsening at 5 years was significantly higher in Q1 vs Q4 (HR: 0.566 [95% CI 0.386, 0.830]; P=0.0036).
Conclusions: These analyses provide further evidence of the association between BVL and later disability worsening. Greater rates of BVL over 2 years are predictive of longer term disability worsening at 5 years in the TEMSO extension.
Disclosure: Study supported by Sanofi Genzyme.
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.
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).
KT: Employee of Sanofi Genzyme.
MAP: Employee of Sanofi Genzyme.
SC: Employee of Sanofi Genzyme, with ownership interests.
JSW: Within the last 3 years, consulting agreements (AbbVie, Actelion, Alkermes, Athersys, Inc., Bayer HeathCare, EMD Serono, Forward Pharma, Genzyme, Novartis, Roche, Taketa, Teva, XenoPort); contracted research (Genzyme, National Institutes of Health, National MS Society); royalties (for monoclonal antibodies out-licensed to Chemicon International), through the University of Texas Health Science Center at Houston.