Contributions
Abstract: P736
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In CARE-MS II (NCT00548405), alemtuzumab significantly improved clinical outcomes vs SC IFNB-1a over 2 years (y) in patients (pts) with active RRMS and inadequate response to prior therapy. Durable efficacy of alemtuzumab was demonstrated over 6 y in a completed extension study (NCT00930553; 2-y core study 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 7-y efficacy/safety of alemtuzumab in CARE-MS II pts who received alemtuzumab.
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); MRI scans were done annually. 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 (AEs).
Results: 338/393 (86%) CARE-MS II pts who entered the extension remained on study until end of Y6 and then entered TOPAZ; 317 (94%) remained on study through Y7. ARR remained low (0.14 at Y7); proportion of pts with stable or improved EDSS remained high (Y7: 73%). Through 7 y, 69% of pts were free from 6-month CDW, 44% achieved 6-month CDI, and the majority achieved NEDA each year. These effects were achieved with 47% of pts receiving no additional treatment (alemtuzumab or other DMT) after their initial 2 courses of alemtuzumab. Incidences of overall AEs, infusion-associated reactions, and infections decreased over time and were reduced vs the 2-y core study. Thyroid AE incidence peaked at Y3 and then declined.
Conclusion: Clinical efficacy of alemtuzumab was maintained for 7 y in pts who had inadequate response to prior therapy, despite 47% receiving no additional treatment since the initial 2 courses of alemtuzumab. 44% of pts also showed improvement in disability. These findings suggest that 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:
BVS: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Pfizer, Novartis, Sanofi Genzyme, and Teva), and research support (Acorda, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme).
RA: Speaker honoria, scientific advisory boards, and research grants (Bayer, Biogen, Biologix, Genpharm, GSK, Lundbeck, Merck Serono, Novartis, and Sanofi Genzyme).
DB: Compensation for advisory board participation, lecture, and travel (Bayer, Biogen, Merck, 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 Genzyme); and unencumbered research grant (Biogen).
H-PH: Consulting and/or speaking fees (Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme).
EH: Honoraria and grant support (Actelion, Biogen, Merck Serono, Novartis, Receptos, Roche, Sanofi Genzyme, and Teva), and supported by Ministry of Education of Czech Republic.
HJK: Consultant and speaking fees (Bayer Schering Pharma, Biogen, Sanofi Genzyme, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Teva-Handok, and UCB); grant and/or research funding (ICT and Future Planning, Kael-GemVax, Merck Serono, Ministry of Science, Sanofi Genzyme, Teva-Handok, and UCB); steering committee member (MedImmune); co-editor/associated editor (MS Journal-Experimental, Translational and Clinical; and Journal of Clinical Neurology).
COG: Speaker honoraria and compensation for consulting services (Alexion, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva).
CP: Consulting and/or speaking fees, research, and travel grants (Actelion, Biogen, Merck, Novartis, Sanofi Genzyme, and Teva).
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).
SW: Consultant, principal investigator, and/or speaker fees (Alkermes, Bayer, Biogen, EMD Serono, Genentech/Roche, Novartis, Sanofi Genzyme, and Teva).
DHM, ND, and MC: Employees of Sanofi.
AJC: Consulting fees, grant support, and lecture fees (Bayer Schering Pharma and Sanofi Genzyme), on behalf of the University of Cambridge; and personal remuneration for lecture fees from July 2014.
Abstract: P736
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In CARE-MS II (NCT00548405), alemtuzumab significantly improved clinical outcomes vs SC IFNB-1a over 2 years (y) in patients (pts) with active RRMS and inadequate response to prior therapy. Durable efficacy of alemtuzumab was demonstrated over 6 y in a completed extension study (NCT00930553; 2-y core study 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 7-y efficacy/safety of alemtuzumab in CARE-MS II pts who received alemtuzumab.
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); MRI scans were done annually. 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 (AEs).
Results: 338/393 (86%) CARE-MS II pts who entered the extension remained on study until end of Y6 and then entered TOPAZ; 317 (94%) remained on study through Y7. ARR remained low (0.14 at Y7); proportion of pts with stable or improved EDSS remained high (Y7: 73%). Through 7 y, 69% of pts were free from 6-month CDW, 44% achieved 6-month CDI, and the majority achieved NEDA each year. These effects were achieved with 47% of pts receiving no additional treatment (alemtuzumab or other DMT) after their initial 2 courses of alemtuzumab. Incidences of overall AEs, infusion-associated reactions, and infections decreased over time and were reduced vs the 2-y core study. Thyroid AE incidence peaked at Y3 and then declined.
Conclusion: Clinical efficacy of alemtuzumab was maintained for 7 y in pts who had inadequate response to prior therapy, despite 47% receiving no additional treatment since the initial 2 courses of alemtuzumab. 44% of pts also showed improvement in disability. These findings suggest that 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:
BVS: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Pfizer, Novartis, Sanofi Genzyme, and Teva), and research support (Acorda, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme).
RA: Speaker honoria, scientific advisory boards, and research grants (Bayer, Biogen, Biologix, Genpharm, GSK, Lundbeck, Merck Serono, Novartis, and Sanofi Genzyme).
DB: Compensation for advisory board participation, lecture, and travel (Bayer, Biogen, Merck, 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 Genzyme); and unencumbered research grant (Biogen).
H-PH: Consulting and/or speaking fees (Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme).
EH: Honoraria and grant support (Actelion, Biogen, Merck Serono, Novartis, Receptos, Roche, Sanofi Genzyme, and Teva), and supported by Ministry of Education of Czech Republic.
HJK: Consultant and speaking fees (Bayer Schering Pharma, Biogen, Sanofi Genzyme, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Teva-Handok, and UCB); grant and/or research funding (ICT and Future Planning, Kael-GemVax, Merck Serono, Ministry of Science, Sanofi Genzyme, Teva-Handok, and UCB); steering committee member (MedImmune); co-editor/associated editor (MS Journal-Experimental, Translational and Clinical; and Journal of Clinical Neurology).
COG: Speaker honoraria and compensation for consulting services (Alexion, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva).
CP: Consulting and/or speaking fees, research, and travel grants (Actelion, Biogen, Merck, Novartis, Sanofi Genzyme, and Teva).
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).
SW: Consultant, principal investigator, and/or speaker fees (Alkermes, Bayer, Biogen, EMD Serono, Genentech/Roche, Novartis, Sanofi Genzyme, and Teva).
DHM, ND, and MC: Employees of Sanofi.
AJC: Consulting fees, grant support, and lecture fees (Bayer Schering Pharma and Sanofi Genzyme), on behalf of the University of Cambridge; and personal remuneration for lecture fees from July 2014.