Contributions
Abstract: P727
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: Alemtuzumab improved clinical and MRI outcomes in two, 2-year (y), phase 3 trials vs SC IFNB-1a in patients (pts) with active RRMS who were treatment-naive (CARE-MS I; NCT00530348) or had inadequate response to prior therapy (CARE-MS II; NCT00548405). Pts continuing in an extension study (NCT0090553) demonstrated durable efficacy through Y6; 24% of pts from CARE-MS I and 30% of pts from CARE-MS II received 1 alemtuzumab retreatment through Y6.
Goal: Evaluate efficacy of alemtuzumab retreatment in pooled CARE-MS I and II pts who received a third course (C3) due to relapse and/or MRI activity.
Methods: Pts received 2 courses of alemtuzumab 12 mg/d (baseline: 5 d; 12 months (mo) later: 3 d) in CARE-MS I and II. Pts who completed the core studies could enter the extension and receive as-needed alemtuzumab retreatment (for relapse and/or MRI activity) or another DMT (per investigator discretion). Assessments in pts who received C3 during the extension: annualised relapse rate (ARR) 12 mo prior/up to 3 y after C3, change in mean EDSS, improved/stable EDSS (vs core study baseline) 12 mo prior/12 mo after C3, and 6-month confirmed disability improvement (CDI) 12 mo prior/12 mo after C3. Pts who received >3 courses (>1 retreatment) or another DMT during the extension were not included in this analysis.
Results: Through Y6, 669/742 (90%) pooled CARE-MS I and II pts entering the extension remained on study. 198/742 (27%) pooled CARE-MS I and II pts received 1 additional course of alemtuzumab (Y2: 2%, Y3: 31%, Y4: 27%, Y5: 23%, Y6: 17%) without further retreatment or other DMT. Mean time from C2 to C3 was 2.6 y. ARR decreased from 0.74 12 mo prior to C3 to 0.06 12 mo after C3 (rate ratio [95% CI], 0.09 [0.046-0.161]; P< 0.0001]), and remained low (0.08) 3 y after C3. Change in mean EDSS 12 mo after C3 was −0.12. The percentage of pts with stable/improved EDSS was higher 12 mo after C3 vs at the time of C3 administration (71% vs 62%). The percentage of pts with CDI was significantly higher 12 mo after C3 vs 12 mo prior to C3 (17.5% vs 5.0%; P=0.0117).
Conclusion: In CARE-MS pts who received a third course due to relapse and/or MRI activity, alemtuzumab effectively reduced relapses and improved disability without further treatment. These data support administering a third course of alemtuzumab in pts with disease activity to achieve durable disease control.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure:
AT: Consulting and/or speaking fees, and grant/research support (Biogen, Chugai, Roche, Sanofi Genzyme, and Teva).
AB: Consulting fees and/or fees for non-CME services (Biogen, Mallinckrodt, Medtronic, Novartis, Sanofi Genzyme, and Teva).
ADB: Consulting fees/fees for non-CME services from commercial interest or their agents/grant and research support (Biogen, Mallinckrodt, Novartis, Roche-Genentech, Sanofi Genzyme, and Teva Neuroscience).
RB: Advisory boards and consulting (Acorda, Avanir, Bayer, Biogen, Novartis, Questcor, Sanofi Genzyme, and Teva).
GC: Consulting fees (Actelion, Bayer, Merck Serono, Novartis, Sanofi Genzyme, and Teva); lecture fees (Bayer, Biogen Dompé, Merck Serono, Novartis, Sanofi Genzyme, Serono Symposia International Foundation, and Teva).
OF: Speaking and/or consulting (Allergan, Almirall, Bayer-Schering, Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva); compensation for serving as a journal editor, associate editor, or member of an editorial advisory board (Revista Española de Esclerosis Múltiple); and research support (Hospital Foundation FIMABIS).
HJK: Consulting and/or speaking fees (Bayer, Biogen, Genzyme, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Teva-Handok, and UCB); research support (Genzyme, ICT & Future Planning, Kael-GemVax, Merck Serono, Ministry of Science, Teva-Handok, and UCB); steering committee member (MedImmune); co-editor (Multiple Sclerosis Journal - Experimental, Translational, and Clinical); and associate editor (Journal of Clinical Neurology).
VL: Honoraria for consulting and speaking at symposia (Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi, Sanofi Genzyme, and Teva, with approval by the HR-Department, Cologne General Hospital, and University of Cologne).
JL: Lecture honoraria (Novartis) and unconditional research support (Biogen, Novartis, and Teva).
RALM: Compensation for advisory board and/or speaking fees (Bayer, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva); research support (Biogen, Merck, Novartis, Sanofi Genzyme, and Teva).
BSh: Nothing to disclose.
PV: Consulting fees (Almirall, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva), and/or research support (Biogen, Roche, and Sanofi Genzyme).
HW: Consulting and/or speaking fees (Bayer, Biogen, Behring, EMD Serono, Fresenius Medical Care, Merck Serono, Novartis, Sanofi Genzyme, Roche, and Teva); license fee payments (Huber-Verlag); and grant/research support (Neotope Bioscience, Novartis, and PML Consortium).
TZ: Consulting and/or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva); grant/research support (Biogen, Novartis, Sanofi Genzyme, and Teva).
MM and ND: Employees of Sanofi.
BSi: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Novartis, Sanofi Genzyme, and Teva), and research support (Acorda, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme).
Abstract: P727
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: Alemtuzumab improved clinical and MRI outcomes in two, 2-year (y), phase 3 trials vs SC IFNB-1a in patients (pts) with active RRMS who were treatment-naive (CARE-MS I; NCT00530348) or had inadequate response to prior therapy (CARE-MS II; NCT00548405). Pts continuing in an extension study (NCT0090553) demonstrated durable efficacy through Y6; 24% of pts from CARE-MS I and 30% of pts from CARE-MS II received 1 alemtuzumab retreatment through Y6.
Goal: Evaluate efficacy of alemtuzumab retreatment in pooled CARE-MS I and II pts who received a third course (C3) due to relapse and/or MRI activity.
Methods: Pts received 2 courses of alemtuzumab 12 mg/d (baseline: 5 d; 12 months (mo) later: 3 d) in CARE-MS I and II. Pts who completed the core studies could enter the extension and receive as-needed alemtuzumab retreatment (for relapse and/or MRI activity) or another DMT (per investigator discretion). Assessments in pts who received C3 during the extension: annualised relapse rate (ARR) 12 mo prior/up to 3 y after C3, change in mean EDSS, improved/stable EDSS (vs core study baseline) 12 mo prior/12 mo after C3, and 6-month confirmed disability improvement (CDI) 12 mo prior/12 mo after C3. Pts who received >3 courses (>1 retreatment) or another DMT during the extension were not included in this analysis.
Results: Through Y6, 669/742 (90%) pooled CARE-MS I and II pts entering the extension remained on study. 198/742 (27%) pooled CARE-MS I and II pts received 1 additional course of alemtuzumab (Y2: 2%, Y3: 31%, Y4: 27%, Y5: 23%, Y6: 17%) without further retreatment or other DMT. Mean time from C2 to C3 was 2.6 y. ARR decreased from 0.74 12 mo prior to C3 to 0.06 12 mo after C3 (rate ratio [95% CI], 0.09 [0.046-0.161]; P< 0.0001]), and remained low (0.08) 3 y after C3. Change in mean EDSS 12 mo after C3 was −0.12. The percentage of pts with stable/improved EDSS was higher 12 mo after C3 vs at the time of C3 administration (71% vs 62%). The percentage of pts with CDI was significantly higher 12 mo after C3 vs 12 mo prior to C3 (17.5% vs 5.0%; P=0.0117).
Conclusion: In CARE-MS pts who received a third course due to relapse and/or MRI activity, alemtuzumab effectively reduced relapses and improved disability without further treatment. These data support administering a third course of alemtuzumab in pts with disease activity to achieve durable disease control.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure:
AT: Consulting and/or speaking fees, and grant/research support (Biogen, Chugai, Roche, Sanofi Genzyme, and Teva).
AB: Consulting fees and/or fees for non-CME services (Biogen, Mallinckrodt, Medtronic, Novartis, Sanofi Genzyme, and Teva).
ADB: Consulting fees/fees for non-CME services from commercial interest or their agents/grant and research support (Biogen, Mallinckrodt, Novartis, Roche-Genentech, Sanofi Genzyme, and Teva Neuroscience).
RB: Advisory boards and consulting (Acorda, Avanir, Bayer, Biogen, Novartis, Questcor, Sanofi Genzyme, and Teva).
GC: Consulting fees (Actelion, Bayer, Merck Serono, Novartis, Sanofi Genzyme, and Teva); lecture fees (Bayer, Biogen Dompé, Merck Serono, Novartis, Sanofi Genzyme, Serono Symposia International Foundation, and Teva).
OF: Speaking and/or consulting (Allergan, Almirall, Bayer-Schering, Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva); compensation for serving as a journal editor, associate editor, or member of an editorial advisory board (Revista Española de Esclerosis Múltiple); and research support (Hospital Foundation FIMABIS).
HJK: Consulting and/or speaking fees (Bayer, Biogen, Genzyme, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Teva-Handok, and UCB); research support (Genzyme, ICT & Future Planning, Kael-GemVax, Merck Serono, Ministry of Science, Teva-Handok, and UCB); steering committee member (MedImmune); co-editor (Multiple Sclerosis Journal - Experimental, Translational, and Clinical); and associate editor (Journal of Clinical Neurology).
VL: Honoraria for consulting and speaking at symposia (Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi, Sanofi Genzyme, and Teva, with approval by the HR-Department, Cologne General Hospital, and University of Cologne).
JL: Lecture honoraria (Novartis) and unconditional research support (Biogen, Novartis, and Teva).
RALM: Compensation for advisory board and/or speaking fees (Bayer, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva); research support (Biogen, Merck, Novartis, Sanofi Genzyme, and Teva).
BSh: Nothing to disclose.
PV: Consulting fees (Almirall, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva), and/or research support (Biogen, Roche, and Sanofi Genzyme).
HW: Consulting and/or speaking fees (Bayer, Biogen, Behring, EMD Serono, Fresenius Medical Care, Merck Serono, Novartis, Sanofi Genzyme, Roche, and Teva); license fee payments (Huber-Verlag); and grant/research support (Neotope Bioscience, Novartis, and PML Consortium).
TZ: Consulting and/or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva); grant/research support (Biogen, Novartis, Sanofi Genzyme, and Teva).
MM and ND: Employees of Sanofi.
BSi: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Novartis, Sanofi Genzyme, and Teva), and research support (Acorda, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme).