Contributions
Abstract: P1181
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Brain volume loss (BVL, which is a measure of brain atrophy) occurs more rapidly in patients with relapsing-remitting multiple sclerosis (RRMS) (0.5%-1.35% per year) than in healthy individuals (0.1%-0.3% per year). Patients with active RRMS who were treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response (≥1 relapse) to prior therapy at baseline (BL) (CARE-MS II; NCT00548405) demonstrated improved clinical and MRI efficacy outcomes following treatment with alemtuzumab versus subcutaneous interferon beta-1a over 2 years. MRI efficacy outcomes included significant slowing of BVL. An extension study (NCT00930553) has shown durable efficacy through 5 years in the absence of continuous treatment.
Goal: To evaluate the effect of alemtuzumab on BVL over 6 years.
Methods: In the CARE-MS studies, patients received 2 courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days). Patients who completed the studies could enter the extension study, with as-needed alemtuzumab for relapse or MRI activity. Alternate disease-modifying therapy could be provided per investigator discretion. MRI scans were performed at BL and annually thereafter. BVL was derived by relative change in brain parenchymal fraction.
Results: 349 (95%) CARE-MS I and 393 (93%) CARE-MS II alemtuzumab-treated patients entered the extension study. Through 6 years, 325/349 (93%) CARE-MS I and 344/393 (88%) CARE-MS II remained on study. In patients who were treatment-naïve (CARE-MS I), alemtuzumab consistently slowed median yearly BVL over 4 years, with BVL remaining low in Years 5 and 6 (Year 1: -0.59%, Year 2: -0.25%, Year 3: -0.19%, Year 4: -0.14%, Year 5: -0.20%, Year 6: -0.17%). In patients who had an inadequate response to therapy prior to BL (CARE-MS II), median yearly BVL progressively decreased over 3 years and remained low in Years 4, 5, and 6 (Year 1: -0.48%, Year 2: -0.22%, Year 3: -0.10%, Year 4: -0.19%, Year 5: -0.07%, Year 6: -0.10%). These effects were achieved with 63% (CARE-MS I) and 50% (CARE-MS II) of patients receiving no additional treatment after their initial 2 courses of alemtuzumab.
Conclusion: Slowing of BVL with alemtuzumab was maintained over 6 years. Median annual BVL was ≤0.2% in Years 3-6, despite ≥50% of patients receiving no additional treatment since the initial 2 courses of alemtuzumab. Based on these findings, alemtuzumab may provide uniquely durable efficacy in the absence of continuous treatment for RRMS patients.
Disclosure: STUDY SUPPORT: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
AT: Consulting fees (Biogen, Novartis, Roche, Sanofi Genzyme, Serono, and Teva); grant/research support (Roche and Sanofi Genzyme). MB: Research support (Biogen, Novartis, and Sanofi Genzyme); speaking fees and participation in advisory boards (Biogen, Novartis, and Sanofi Genzyme); research consultant (Medical Safety Systems). GC: Consulting fees (Actelion, Bayer Schering, Merck Serono, Novartis, Sanofi, and Teva Pharmaceuticals Ind. Ltd), lecture fees (Bayer Schering, Biogen Dompé, Merck Serono, Novartis, Sanofi, Serono Symposia International Foundation, and Teva Pharmaceuticals Ind. Ltd). CL: Compensation for consulting (Acorda Therapeutics, Bayer, Biogen, Cephalon, EMD Serono, Novartis, Pfizer, Questcor, Sanofi Genzyme, Strativa, Teva, and UCB). DP: Consulting and/or speaking fees (Biogen, EMD Serono, Novartis, Roche, Sanofi Genzyme, and Vertex); grant/research support (Biogen). AR: Consulting and/or speaking fees (Bayer, Biogen, Bracco, Novartis, Sanofi Genzyme, and Stendhal). SS: Consulting and/or speaking fees (Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva); grant/research support (Novartis, Sanofi Genzyme). DHM and KT: Employees of Sanofi Genzyme. KN: Consulting (NeuroRx); research support (Biogen, Sanofi Genzyme). DLA: Compensation for serving as a speaker, consulting, and advisory board participant, and receiving research support (Acorda, Bayer, Biogen, Canadian Institutes of Health Research, Eli Lilly, EMD Serono, Genentech, GlaxoSmith Kline, MedImmune, Merck Serono, MS Society of Canada, NeuroRX Research, Novartis, Opexa Therapeutics, Receptos, Roche, Sanofi Genzyme, and Teva).
Abstract: P1181
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Brain volume loss (BVL, which is a measure of brain atrophy) occurs more rapidly in patients with relapsing-remitting multiple sclerosis (RRMS) (0.5%-1.35% per year) than in healthy individuals (0.1%-0.3% per year). Patients with active RRMS who were treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response (≥1 relapse) to prior therapy at baseline (BL) (CARE-MS II; NCT00548405) demonstrated improved clinical and MRI efficacy outcomes following treatment with alemtuzumab versus subcutaneous interferon beta-1a over 2 years. MRI efficacy outcomes included significant slowing of BVL. An extension study (NCT00930553) has shown durable efficacy through 5 years in the absence of continuous treatment.
Goal: To evaluate the effect of alemtuzumab on BVL over 6 years.
Methods: In the CARE-MS studies, patients received 2 courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days). Patients who completed the studies could enter the extension study, with as-needed alemtuzumab for relapse or MRI activity. Alternate disease-modifying therapy could be provided per investigator discretion. MRI scans were performed at BL and annually thereafter. BVL was derived by relative change in brain parenchymal fraction.
Results: 349 (95%) CARE-MS I and 393 (93%) CARE-MS II alemtuzumab-treated patients entered the extension study. Through 6 years, 325/349 (93%) CARE-MS I and 344/393 (88%) CARE-MS II remained on study. In patients who were treatment-naïve (CARE-MS I), alemtuzumab consistently slowed median yearly BVL over 4 years, with BVL remaining low in Years 5 and 6 (Year 1: -0.59%, Year 2: -0.25%, Year 3: -0.19%, Year 4: -0.14%, Year 5: -0.20%, Year 6: -0.17%). In patients who had an inadequate response to therapy prior to BL (CARE-MS II), median yearly BVL progressively decreased over 3 years and remained low in Years 4, 5, and 6 (Year 1: -0.48%, Year 2: -0.22%, Year 3: -0.10%, Year 4: -0.19%, Year 5: -0.07%, Year 6: -0.10%). These effects were achieved with 63% (CARE-MS I) and 50% (CARE-MS II) of patients receiving no additional treatment after their initial 2 courses of alemtuzumab.
Conclusion: Slowing of BVL with alemtuzumab was maintained over 6 years. Median annual BVL was ≤0.2% in Years 3-6, despite ≥50% of patients receiving no additional treatment since the initial 2 courses of alemtuzumab. Based on these findings, alemtuzumab may provide uniquely durable efficacy in the absence of continuous treatment for RRMS patients.
Disclosure: STUDY SUPPORT: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
AT: Consulting fees (Biogen, Novartis, Roche, Sanofi Genzyme, Serono, and Teva); grant/research support (Roche and Sanofi Genzyme). MB: Research support (Biogen, Novartis, and Sanofi Genzyme); speaking fees and participation in advisory boards (Biogen, Novartis, and Sanofi Genzyme); research consultant (Medical Safety Systems). GC: Consulting fees (Actelion, Bayer Schering, Merck Serono, Novartis, Sanofi, and Teva Pharmaceuticals Ind. Ltd), lecture fees (Bayer Schering, Biogen Dompé, Merck Serono, Novartis, Sanofi, Serono Symposia International Foundation, and Teva Pharmaceuticals Ind. Ltd). CL: Compensation for consulting (Acorda Therapeutics, Bayer, Biogen, Cephalon, EMD Serono, Novartis, Pfizer, Questcor, Sanofi Genzyme, Strativa, Teva, and UCB). DP: Consulting and/or speaking fees (Biogen, EMD Serono, Novartis, Roche, Sanofi Genzyme, and Vertex); grant/research support (Biogen). AR: Consulting and/or speaking fees (Bayer, Biogen, Bracco, Novartis, Sanofi Genzyme, and Stendhal). SS: Consulting and/or speaking fees (Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva); grant/research support (Novartis, Sanofi Genzyme). DHM and KT: Employees of Sanofi Genzyme. KN: Consulting (NeuroRx); research support (Biogen, Sanofi Genzyme). DLA: Compensation for serving as a speaker, consulting, and advisory board participant, and receiving research support (Acorda, Bayer, Biogen, Canadian Institutes of Health Research, Eli Lilly, EMD Serono, Genentech, GlaxoSmith Kline, MedImmune, Merck Serono, MS Society of Canada, NeuroRX Research, Novartis, Opexa Therapeutics, Receptos, Roche, Sanofi Genzyme, and Teva).