Contributions
Abstract: P1194
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In CARE-MS II (NCT00548405), alemtuzumab significantly improved clinical outcomes versus SC IFNB-1a over 2 years (y) in patients (pts) with active RRMS and inadequate response to prior therapy. In a completed extension (NCT00930553), SC IFNB-1a-treated pts discontinued that therapy and initiated alemtuzumab 12 mg (2 courses: baseline, 5 days; 12 months later, 3 days), which demonstrated durable efficacy in the absence of continuous treatment. In the extension, pts could receive as-needed alemtuzumab retreatment (12 mg/day on 3 consecutive days ≥12 months after previous course for relapse/MRI activity) or other disease-modifying therapy (DMT; per investigator discretion). Pts completing ≥48 months of extension could enrol in TOPAZ, a 5-y, phase 3b/4 study (NCT02255656), for further evaluation.
Goal: Evaluate alemtuzumab efficacy and safety 5 y after switching from SC IFNB-1a.
Methods: In TOPAZ, pts can receive alemtuzumab retreatment (≥12 months apart) or other DMT at any time point (both per investigator discretion, no criteria); MRI scans were annual. Assessments: annualised relapse rate (ARR); 6-month confirmed disability worsening (CDW); 6-month confirmed disability improvement (CDI); no evidence of disease activity (NEDA); adverse events.
Results: Of 175 SC IFNB-1a-treated pts completing CARE-MS II, 143 (82%) received alemtuzumab in the extension study; 123 (86%) of these completed Y4 post-alemtuzumab and entered TOPAZ; 119 (97%) completed Y5 post-alemtuzumab. ARR decreased from 0.52 with SC IFNB-1a (Y0-2) to 0.15 with alemtuzumab (Y0-2) and remained low through Y5 (0.18). Percentage relapse-free increased from 70% in Y2 of SC IFNB-1a to 85% in Y2 post-alemtuzumab and was 83% in Y5. Percentages achieving annual NEDA increased from 32% in Y2 of SC IFNB-1a to 66%, 63%, 59%, and 55% in Y2, Y3, Y4, and Y5 post-alemtuzumab, respectively. Through Y5 of alemtuzumab follow-up, 74% were free of 6-month CDW; 23% had 6-month CDI. 61% received no further treatment after the initial 2 courses. Safety was consistent with core study alemtuzumab-treated pts.
Conclusion: In pts with an inadequate response to prior therapy and an additional 2 y of SC IFNB-1a, subsequent clinical outcomes after alemtuzumab were improved over 5 y. These findings are consistent with core study conclusions and suggest that alemtuzumab may provide a unique treatment approach for RRMS pts treated previously with SC IFNB-1a, with durable efficacy in the absence of continuous treatment.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure:
BvW: Received research and travel grants, honoraria for MS-expert advice, and speaker fees (Bayer-Schering, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva).
ANB: Consulting fees/participated in clinical trials (Bayer, Biogen, Merck Serono, Novartis, Sanofi Aventis, Sanofi Genzyme, and Teva).
DB: Advisory board participant, lecture and travel fees (Bayer, Biogen, Merck, Sanofi Genzyme, and Teva).
DD: Institutional honoraria for advisory board participation and travel grants (Bayer, Merck Serono, Novartis, Sanofi Genzyme, and Teva).
SB: Honoraria for participation in advisory boards (Bayer-Schering, Biogen, Merck Serono, Novartis, and Sanofi Genzyme); conference travel sponsorship (Bayer-Schering, Biogen, Merck Serono, Novartis, and Sanofi Genzyme); speaker honoraria (Biogen and Sanofi Genzyme); and unencumbered research grant (Biogen).
RMMH: Research grants, speaker´s fees, and honoraria for advisory boards (Biogen, Merck, Novartis, Sanofi Genzyme, and Teva).
JL: Travel support and/or lecture honoraria (Biogen, Novartis, Sanofi Genzyme, and Teva); scientific advisory boards (Almirall, Biogen, Novartis, Sanofi Genzyme, and Teva); editorial board of Acta Neurologica Scandinavica; and unconditional research grants (Biogen, Novartis, and Teva).
XM: Consulting and/or speaking fees (Almirall, Bayer, Biogen, EMD Serono, Genentech, Geneuro, Merck, Neurotec, Novartis, Roche, Sanofi, Sanofi Genzyme, and Teva).
BS: Nothing to disclose.
SW: Consultant, principal investigator, and speaker (Bayer, Biogen, EMD Serono, Novartis); consultant and principal investigator (Genentech and Roche); principal investigator (Alkermes); and principal investigator and speaker (Teva).
DHM, ND, and MC: Employees of Sanofi.
HW: Consulting and/or speaking fees, and grant/research support (Bayer, Bayer Schering Pharma, Biogen, Elan Corporation, Lilly, Lundbeck, Merck Serono, Novartis, Novo Nordisk, Sanofi, and Teva Neuroscience).
Abstract: P1194
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In CARE-MS II (NCT00548405), alemtuzumab significantly improved clinical outcomes versus SC IFNB-1a over 2 years (y) in patients (pts) with active RRMS and inadequate response to prior therapy. In a completed extension (NCT00930553), SC IFNB-1a-treated pts discontinued that therapy and initiated alemtuzumab 12 mg (2 courses: baseline, 5 days; 12 months later, 3 days), which demonstrated durable efficacy in the absence of continuous treatment. In the extension, pts could receive as-needed alemtuzumab retreatment (12 mg/day on 3 consecutive days ≥12 months after previous course for relapse/MRI activity) or other disease-modifying therapy (DMT; per investigator discretion). Pts completing ≥48 months of extension could enrol in TOPAZ, a 5-y, phase 3b/4 study (NCT02255656), for further evaluation.
Goal: Evaluate alemtuzumab efficacy and safety 5 y after switching from SC IFNB-1a.
Methods: In TOPAZ, pts can receive alemtuzumab retreatment (≥12 months apart) or other DMT at any time point (both per investigator discretion, no criteria); MRI scans were annual. Assessments: annualised relapse rate (ARR); 6-month confirmed disability worsening (CDW); 6-month confirmed disability improvement (CDI); no evidence of disease activity (NEDA); adverse events.
Results: Of 175 SC IFNB-1a-treated pts completing CARE-MS II, 143 (82%) received alemtuzumab in the extension study; 123 (86%) of these completed Y4 post-alemtuzumab and entered TOPAZ; 119 (97%) completed Y5 post-alemtuzumab. ARR decreased from 0.52 with SC IFNB-1a (Y0-2) to 0.15 with alemtuzumab (Y0-2) and remained low through Y5 (0.18). Percentage relapse-free increased from 70% in Y2 of SC IFNB-1a to 85% in Y2 post-alemtuzumab and was 83% in Y5. Percentages achieving annual NEDA increased from 32% in Y2 of SC IFNB-1a to 66%, 63%, 59%, and 55% in Y2, Y3, Y4, and Y5 post-alemtuzumab, respectively. Through Y5 of alemtuzumab follow-up, 74% were free of 6-month CDW; 23% had 6-month CDI. 61% received no further treatment after the initial 2 courses. Safety was consistent with core study alemtuzumab-treated pts.
Conclusion: In pts with an inadequate response to prior therapy and an additional 2 y of SC IFNB-1a, subsequent clinical outcomes after alemtuzumab were improved over 5 y. These findings are consistent with core study conclusions and suggest that alemtuzumab may provide a unique treatment approach for RRMS pts treated previously with SC IFNB-1a, with durable efficacy in the absence of continuous treatment.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure:
BvW: Received research and travel grants, honoraria for MS-expert advice, and speaker fees (Bayer-Schering, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva).
ANB: Consulting fees/participated in clinical trials (Bayer, Biogen, Merck Serono, Novartis, Sanofi Aventis, Sanofi Genzyme, and Teva).
DB: Advisory board participant, lecture and travel fees (Bayer, Biogen, Merck, Sanofi Genzyme, and Teva).
DD: Institutional honoraria for advisory board participation and travel grants (Bayer, Merck Serono, Novartis, Sanofi Genzyme, and Teva).
SB: Honoraria for participation in advisory boards (Bayer-Schering, Biogen, Merck Serono, Novartis, and Sanofi Genzyme); conference travel sponsorship (Bayer-Schering, Biogen, Merck Serono, Novartis, and Sanofi Genzyme); speaker honoraria (Biogen and Sanofi Genzyme); and unencumbered research grant (Biogen).
RMMH: Research grants, speaker´s fees, and honoraria for advisory boards (Biogen, Merck, Novartis, Sanofi Genzyme, and Teva).
JL: Travel support and/or lecture honoraria (Biogen, Novartis, Sanofi Genzyme, and Teva); scientific advisory boards (Almirall, Biogen, Novartis, Sanofi Genzyme, and Teva); editorial board of Acta Neurologica Scandinavica; and unconditional research grants (Biogen, Novartis, and Teva).
XM: Consulting and/or speaking fees (Almirall, Bayer, Biogen, EMD Serono, Genentech, Geneuro, Merck, Neurotec, Novartis, Roche, Sanofi, Sanofi Genzyme, and Teva).
BS: Nothing to disclose.
SW: Consultant, principal investigator, and speaker (Bayer, Biogen, EMD Serono, Novartis); consultant and principal investigator (Genentech and Roche); principal investigator (Alkermes); and principal investigator and speaker (Teva).
DHM, ND, and MC: Employees of Sanofi.
HW: Consulting and/or speaking fees, and grant/research support (Bayer, Bayer Schering Pharma, Biogen, Elan Corporation, Lilly, Lundbeck, Merck Serono, Novartis, Novo Nordisk, Sanofi, and Teva Neuroscience).