Contributions
Abstract: 213
Type: Oral
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: In the phase 3 CARE-MS I clinical trial (NCT00530348), alemtuzumab significantly reduced annualised relapse rate (ARR), MRI disease activity, and brain volume loss versus subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting multiple sclerosis (RRMS) who were treatment-naive at baseline (BL). An extension study (NCT00930553) has shown durable efficacy through 5 years in the absence of continuous treatment.
Goal: To evaluate 6-year clinical efficacy and safety of alemtuzumab in patients who were treatment-naive at BL.
Methods: In CARE-MS I, patients received 2 courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days). At the end of Year 2, patients who completed the study could enter the extension, with as-needed alemtuzumab for relapse or MRI activity. Another disease-modifying therapy could be provided per investigator discretion. Assessments: ARR, proportion of patients free from 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] increase [≥1.5-point if BL EDSS=0]), with 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [BL score ≥2.0]), no evidence of disease activity (NEDA), and adverse events (AEs).
Results: Through 6 years, 325/349 (93%) patients who enrolled in the extension remained on study. ARR remained low through the extension (0.12 at Year 6). Through 6 years, 77% of patients were free from 6-month CDW and 34% achieved 6-month CDI. Proportions of patients with stable or improved EDSS remained high through the extension (81% at Year 6); the majority of patients achieved NEDA annually in the extension (57% at Year 6). These efficacy results were achieved with most patients (63%) receiving no additional treatment after their initial 2 courses of alemtuzumab. The overall rate of AEs decreased over time. The rate of thyroid AEs peaked at Year 3 and subsequently declined. Infusion-associated reactions decreased with additional treatment courses. The serious AE rate was low, including the rate of serious infections, which declined throughout the extension.
Conclusion: Clinical efficacy of alemtuzumab was maintained for 6 years in patients who were treatment-naive, despite most receiving no additional treatment since the initial 2 courses of alemtuzumab. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for RRMS patients.
Disclosure:
Study support: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
AJC: Consulting fees, lecture fees, and institutional grant support (Sanofi Genzyme).
ANB: Consulting fees/participated in clinical trials (Bayer, Biogen, Merck Serono, Novartis, Sanofi-Aventis, Sanofi Genzyme, and Teva Pharmaceuticals).
JAC: Consulting and/or speaking fees (Genentech, Novartis, Sanofi Genzyme); and compensation for serving as a journal editor, associate editor, or member of an editorial advisory board (Multiple Sclerosis Journal: Experimental, Translational and Clinical).
JDS: Consulting and/or speaking fees, advisory board, and grant/research support (Sanofi Genzyme).
EJF: Consulting and/or speaking fees, and grant/research support (Acorda, Bayer, Biogen, Chugai, Eli Lilly, EMD Serono, Genentech, Novartis, Opexa, Roche, Sanofi, Sanofi Genzyme, and Teva Pharmaceuticals).
EH: Honoraria and grant support (Actelion, Biogen, Merck Serono, Novartis, Receptos, Roche, Sanofi Genzyme, and Teva) and is supported by Ministry of Education of Czech Republic.
H-PH: Consulting and/or speaking fees (Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme).
JSI: Nothing to disclose.
PM: Consulting and/or speaking fees (Biogen, Novartis, Sanofi-Aventis, and Teva Pharmaceuticals).
KWS: Consulting and/or speaking fees (Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Synthon).
PV: Consulting and/or speaking fees, and research support (Almirall, Bayer, Biogen, GlaxoSmithKline, Merck Serono, Novartis, Sanofi Genzyme, and Teva).
BVW: Received research and travel grants, honoraria for MS-expert advice, and speakers fees (Bayer-Schering, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva).
DHM, KT, and CER: Employees of Sanofi Genzyme.
XM: Consulting and/or speaking fees (Almirall, Bayer, Biogen, EMD, Genentech, Geneuro, Merck, Neurotec, Novartis, Roche, Sanofi, Sanofi Genzyme, and Teva Pharmaceuticals).
Abstract: 213
Type: Oral
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: In the phase 3 CARE-MS I clinical trial (NCT00530348), alemtuzumab significantly reduced annualised relapse rate (ARR), MRI disease activity, and brain volume loss versus subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting multiple sclerosis (RRMS) who were treatment-naive at baseline (BL). An extension study (NCT00930553) has shown durable efficacy through 5 years in the absence of continuous treatment.
Goal: To evaluate 6-year clinical efficacy and safety of alemtuzumab in patients who were treatment-naive at BL.
Methods: In CARE-MS I, patients received 2 courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days). At the end of Year 2, patients who completed the study could enter the extension, with as-needed alemtuzumab for relapse or MRI activity. Another disease-modifying therapy could be provided per investigator discretion. Assessments: ARR, proportion of patients free from 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] increase [≥1.5-point if BL EDSS=0]), with 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [BL score ≥2.0]), no evidence of disease activity (NEDA), and adverse events (AEs).
Results: Through 6 years, 325/349 (93%) patients who enrolled in the extension remained on study. ARR remained low through the extension (0.12 at Year 6). Through 6 years, 77% of patients were free from 6-month CDW and 34% achieved 6-month CDI. Proportions of patients with stable or improved EDSS remained high through the extension (81% at Year 6); the majority of patients achieved NEDA annually in the extension (57% at Year 6). These efficacy results were achieved with most patients (63%) receiving no additional treatment after their initial 2 courses of alemtuzumab. The overall rate of AEs decreased over time. The rate of thyroid AEs peaked at Year 3 and subsequently declined. Infusion-associated reactions decreased with additional treatment courses. The serious AE rate was low, including the rate of serious infections, which declined throughout the extension.
Conclusion: Clinical efficacy of alemtuzumab was maintained for 6 years in patients who were treatment-naive, despite most receiving no additional treatment since the initial 2 courses of alemtuzumab. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for RRMS patients.
Disclosure:
Study support: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
AJC: Consulting fees, lecture fees, and institutional grant support (Sanofi Genzyme).
ANB: Consulting fees/participated in clinical trials (Bayer, Biogen, Merck Serono, Novartis, Sanofi-Aventis, Sanofi Genzyme, and Teva Pharmaceuticals).
JAC: Consulting and/or speaking fees (Genentech, Novartis, Sanofi Genzyme); and compensation for serving as a journal editor, associate editor, or member of an editorial advisory board (Multiple Sclerosis Journal: Experimental, Translational and Clinical).
JDS: Consulting and/or speaking fees, advisory board, and grant/research support (Sanofi Genzyme).
EJF: Consulting and/or speaking fees, and grant/research support (Acorda, Bayer, Biogen, Chugai, Eli Lilly, EMD Serono, Genentech, Novartis, Opexa, Roche, Sanofi, Sanofi Genzyme, and Teva Pharmaceuticals).
EH: Honoraria and grant support (Actelion, Biogen, Merck Serono, Novartis, Receptos, Roche, Sanofi Genzyme, and Teva) and is supported by Ministry of Education of Czech Republic.
H-PH: Consulting and/or speaking fees (Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme).
JSI: Nothing to disclose.
PM: Consulting and/or speaking fees (Biogen, Novartis, Sanofi-Aventis, and Teva Pharmaceuticals).
KWS: Consulting and/or speaking fees (Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Synthon).
PV: Consulting and/or speaking fees, and research support (Almirall, Bayer, Biogen, GlaxoSmithKline, Merck Serono, Novartis, Sanofi Genzyme, and Teva).
BVW: Received research and travel grants, honoraria for MS-expert advice, and speakers fees (Bayer-Schering, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva).
DHM, KT, and CER: Employees of Sanofi Genzyme.
XM: Consulting and/or speaking fees (Almirall, Bayer, Biogen, EMD, Genentech, Geneuro, Merck, Neurotec, Novartis, Roche, Sanofi, Sanofi Genzyme, and Teva Pharmaceuticals).