Contributions
Abstract: P741
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In CARE-MS II (NCT00548405), alemtuzumab significantly improved clinical and MRI outcomes, including brain volume loss (BVL), vs SC IFNB-1a over 2 years (y) in active RRMS patients (pts) with inadequate response to prior therapy. Durable efficacy of alemtuzumab was shown over 6 y in a completed extension study (NCT00930553; 2-y core plus 4-y extension) in the absence of continuous treatment. CARE-MS II pts received 2 courses of alemtuzumab 12 mg/day (baseline: 5 days; 12 months later: 3 days). In the extension, pts could receive as-needed alemtuzumab retreatment (12 mg/day on 3 consecutive days; ≥12 months after previous course for relapse or MRI activity) or other disease-modifying therapy (DMT; per investigator discretion). Pts completing at least 48 months of the extension could enrol in the 5-y TOPAZ study (NCT02255656) for further long-term evaluation.
Goal: Evaluate the effect of alemtuzumab on MRI lesion outcomes and BVL over 7 y in pts who received alemtuzumab in CARE-MS II.
Methods: In TOPAZ, pts can receive alemtuzumab retreatment ≥12 months after previous course or other DMT at any time point (both per investigator discretion; no criteria). Assessments: Annual MRI scored for proportions of pts with no evidence of MRI disease activity (no new Gd-enhancing lesions; no new/enlarging T2 lesions); new T1 hypointense lesions; and BVL, derived by relative change in brain parenchymal fraction (BPF).
Results: 338 of 393 (86%) CARE-MS II pts who entered the extension remained on study until the end of Y6 and then entered TOPAZ; 317 (94%) remained on study through Y7. At Y7, 67% of pts each remained free of MRI disease activity and new/enlarging T2 lesions. 90% were free of new Gd-enhancing lesions and 88% were free of new T1 hypointense lesions. Alemtuzumab consistently slowed median yearly BPF change over 2 y, remaining low in Y3-7 (Y1: -0.48%, Y2: -0.22%, Y3: -0.10%, Y4: -0.19%, Y5: -0.07%, Y6: -0.10%, Y7: -0.14%). These results were achieved with 47% of pts receiving no alemtuzumab retreatment or another DMT.
Conclusion: Alemtuzumab durably reduced MRI disease activity and slowed BVL over 7 y in pts with inadequate response to prior therapy, despite 47% receiving no additional treatment after the initial 2 courses of alemtuzumab. These findings suggest alemtuzumab may provide a unique treatment approach for RRMS pts, offering durable efficacy in the absence of continuous treatment.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure:
DP: Consulting and/or speaking fees and grant/research support (Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Vertex).
AT: Consulting and/or speaking fees and grant/research support (Biogen, Chugai, Roche, Sanofi Genzyme, and Teva).
MB: Institutional support for research, speaking, and/or 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); lecture fees (Bayer Schering, Biogen Dompé, Merck Serono, Novartis, Sanofi, Serono Symposia International Foundation, and Teva).
JDS: Consulting and/or speaking fees, advisory board, and grant/research support (Sanofi Genzyme).
AR: Consulting and/or speaking fees (Bayer, Biogen, Bracco, Novartis, Sanofi Genzyme, and Stendhal).
SS: Consulting and/or speaking fees and grant/research support (Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva).
DHM: Employee of Sanofi.
SSa: Provides statistical support as a paid consultant for Sanofi.
KN: Speaking fees and research support (Biogen and Sanofi Genzyme); royalty fees for licences (Biogen).
DLA: Compensation for serving as a speaker, consultant, 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).
Abstract: P741
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In CARE-MS II (NCT00548405), alemtuzumab significantly improved clinical and MRI outcomes, including brain volume loss (BVL), vs SC IFNB-1a over 2 years (y) in active RRMS patients (pts) with inadequate response to prior therapy. Durable efficacy of alemtuzumab was shown over 6 y in a completed extension study (NCT00930553; 2-y core plus 4-y extension) in the absence of continuous treatment. CARE-MS II pts received 2 courses of alemtuzumab 12 mg/day (baseline: 5 days; 12 months later: 3 days). In the extension, pts could receive as-needed alemtuzumab retreatment (12 mg/day on 3 consecutive days; ≥12 months after previous course for relapse or MRI activity) or other disease-modifying therapy (DMT; per investigator discretion). Pts completing at least 48 months of the extension could enrol in the 5-y TOPAZ study (NCT02255656) for further long-term evaluation.
Goal: Evaluate the effect of alemtuzumab on MRI lesion outcomes and BVL over 7 y in pts who received alemtuzumab in CARE-MS II.
Methods: In TOPAZ, pts can receive alemtuzumab retreatment ≥12 months after previous course or other DMT at any time point (both per investigator discretion; no criteria). Assessments: Annual MRI scored for proportions of pts with no evidence of MRI disease activity (no new Gd-enhancing lesions; no new/enlarging T2 lesions); new T1 hypointense lesions; and BVL, derived by relative change in brain parenchymal fraction (BPF).
Results: 338 of 393 (86%) CARE-MS II pts who entered the extension remained on study until the end of Y6 and then entered TOPAZ; 317 (94%) remained on study through Y7. At Y7, 67% of pts each remained free of MRI disease activity and new/enlarging T2 lesions. 90% were free of new Gd-enhancing lesions and 88% were free of new T1 hypointense lesions. Alemtuzumab consistently slowed median yearly BPF change over 2 y, remaining low in Y3-7 (Y1: -0.48%, Y2: -0.22%, Y3: -0.10%, Y4: -0.19%, Y5: -0.07%, Y6: -0.10%, Y7: -0.14%). These results were achieved with 47% of pts receiving no alemtuzumab retreatment or another DMT.
Conclusion: Alemtuzumab durably reduced MRI disease activity and slowed BVL over 7 y in pts with inadequate response to prior therapy, despite 47% receiving no additional treatment after the initial 2 courses of alemtuzumab. These findings suggest alemtuzumab may provide a unique treatment approach for RRMS pts, offering durable efficacy in the absence of continuous treatment.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure:
DP: Consulting and/or speaking fees and grant/research support (Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Vertex).
AT: Consulting and/or speaking fees and grant/research support (Biogen, Chugai, Roche, Sanofi Genzyme, and Teva).
MB: Institutional support for research, speaking, and/or 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); lecture fees (Bayer Schering, Biogen Dompé, Merck Serono, Novartis, Sanofi, Serono Symposia International Foundation, and Teva).
JDS: Consulting and/or speaking fees, advisory board, and grant/research support (Sanofi Genzyme).
AR: Consulting and/or speaking fees (Bayer, Biogen, Bracco, Novartis, Sanofi Genzyme, and Stendhal).
SS: Consulting and/or speaking fees and grant/research support (Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva).
DHM: Employee of Sanofi.
SSa: Provides statistical support as a paid consultant for Sanofi.
KN: Speaking fees and research support (Biogen and Sanofi Genzyme); royalty fees for licences (Biogen).
DLA: Compensation for serving as a speaker, consultant, 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).