Contributions
Abstract: P724
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In CARE-MS II (NCT00548405), alemtuzumab significantly improved MRI outcomes, including brain volume loss (BVL), vs 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. 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 MRI efficacy 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). Assessments: annual MRI scored for disease activity (gadolinium [Gd]-enhancing T1 lesions or new/enlarging T2 hyperintense lesions) and brain parenchymal fraction (BPF) change.
Results: Of 175 SC IFNB-1a-treated pts completing CARE-MS II, 143 (82%) received alemtuzumab in the extension; 123 (86%) of these completed Y4 of post-alemtuzumab follow-up and entered TOPAZ; 119 (97%) completed Y5 post-alemtuzumab. Percentages free of Gd-enhancing T1 lesions were 78% in SC IFNB-1a Y2, increasing to 91% in post-alemtuzumab Y2, and 86%-89% in Y3-5. Percentages free of new/enlarging T2 hyperintense lesions were 48% in SC IFNB-1a Y2, 81% in post-alemtuzumab Y2, and 72%-67% in Y3-5. Percentages free of MRI disease activity increased from 47% in SC IFNB-1a Y2 to 81% in post-alemtuzumab Y2, and were 72%-67% in Y3-5. Median yearly BPF percent change decreased post-alemtuzumab (SC IFNB-1a Y2: -0.33%; alemtuzumab Y1-5: 0.02%, -0.04%, -0.15%, -0.14%, -0.08%). 61% received no further treatment after the initial 2 courses.
Conclusion: In pts with inadequate response to prior therapy plus 2 y of SC IFNB-1a treatment, switching to alemtuzumab improved MRI lesion and BVL outcomes 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, offering durable efficacy in the absence of continuous treatment.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure:
DP: Consulting and/or speaking fees (Biogen, Novartis, Roche, Sanofi Genzyme, and Vertex); grant/research support (Biogen).
MB: Institutional support for research, speaking and/or participation in advisory boards (Biogen, Novartis, and Sanofi Genzyme); research consultant (Medical Safety Systems).
AB: Consulting fees and/or fees for non-CME services (Biogen, Mallinckrodt, Medtronic, Novartis, 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).
H-PH: Consulting and/or speaking fees (Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme).
AR: Consulting and/or speaking fees (Bayer, Biogen, Bracco, Novartis, Sanofi Genzyme, and Stendhal).
SSchippling: Consulting and/or speaking fees (Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva); grant/research support (Novartis and Sanofi Genzyme).
BS: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Novartis, Sanofi Genzyme, and Teva); research support (Acorda, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme).
AT: Consulting fees (Biogen, Novartis, Roche, Sanofi Genzyme, Serono, and Teva); grant/research support (Roche and Sanofi Genzyme).
DHM: Employee of Sanofi.
SSantra: Provides statistical support as a paid consultant for Sanofi Genzyme.
KN: Consulting (NeuroRx) and research support (Biogen and Sanofi Genzyme); royalty on licenses (Biogen).
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, GlaxoSmithKline, MedImmune, Merck Serono, MS Society of Canada, NeuroRx Research, Novartis, Opexa Therapeutics, Receptos, Roche, Sanofi, Sanofi Genzyme, and Teva Pharmaceuticals).
Abstract: P724
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In CARE-MS II (NCT00548405), alemtuzumab significantly improved MRI outcomes, including brain volume loss (BVL), vs 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. 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 MRI efficacy 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). Assessments: annual MRI scored for disease activity (gadolinium [Gd]-enhancing T1 lesions or new/enlarging T2 hyperintense lesions) and brain parenchymal fraction (BPF) change.
Results: Of 175 SC IFNB-1a-treated pts completing CARE-MS II, 143 (82%) received alemtuzumab in the extension; 123 (86%) of these completed Y4 of post-alemtuzumab follow-up and entered TOPAZ; 119 (97%) completed Y5 post-alemtuzumab. Percentages free of Gd-enhancing T1 lesions were 78% in SC IFNB-1a Y2, increasing to 91% in post-alemtuzumab Y2, and 86%-89% in Y3-5. Percentages free of new/enlarging T2 hyperintense lesions were 48% in SC IFNB-1a Y2, 81% in post-alemtuzumab Y2, and 72%-67% in Y3-5. Percentages free of MRI disease activity increased from 47% in SC IFNB-1a Y2 to 81% in post-alemtuzumab Y2, and were 72%-67% in Y3-5. Median yearly BPF percent change decreased post-alemtuzumab (SC IFNB-1a Y2: -0.33%; alemtuzumab Y1-5: 0.02%, -0.04%, -0.15%, -0.14%, -0.08%). 61% received no further treatment after the initial 2 courses.
Conclusion: In pts with inadequate response to prior therapy plus 2 y of SC IFNB-1a treatment, switching to alemtuzumab improved MRI lesion and BVL outcomes 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, offering durable efficacy in the absence of continuous treatment.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure:
DP: Consulting and/or speaking fees (Biogen, Novartis, Roche, Sanofi Genzyme, and Vertex); grant/research support (Biogen).
MB: Institutional support for research, speaking and/or participation in advisory boards (Biogen, Novartis, and Sanofi Genzyme); research consultant (Medical Safety Systems).
AB: Consulting fees and/or fees for non-CME services (Biogen, Mallinckrodt, Medtronic, Novartis, 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).
H-PH: Consulting and/or speaking fees (Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme).
AR: Consulting and/or speaking fees (Bayer, Biogen, Bracco, Novartis, Sanofi Genzyme, and Stendhal).
SSchippling: Consulting and/or speaking fees (Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva); grant/research support (Novartis and Sanofi Genzyme).
BS: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Novartis, Sanofi Genzyme, and Teva); research support (Acorda, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme).
AT: Consulting fees (Biogen, Novartis, Roche, Sanofi Genzyme, Serono, and Teva); grant/research support (Roche and Sanofi Genzyme).
DHM: Employee of Sanofi.
SSantra: Provides statistical support as a paid consultant for Sanofi Genzyme.
KN: Consulting (NeuroRx) and research support (Biogen and Sanofi Genzyme); royalty on licenses (Biogen).
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, GlaxoSmithKline, MedImmune, Merck Serono, MS Society of Canada, NeuroRx Research, Novartis, Opexa Therapeutics, Receptos, Roche, Sanofi, Sanofi Genzyme, and Teva Pharmaceuticals).