Contributions
Abstract: P610
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Disability is a primary contributor to the burden of multiple sclerosis (MS); one of the goals of therapy is thus to improve pre-existing disability. To date, few disease-modifying therapies have demonstrated confirmed disability improvement (CDI). In the CARE-MS II study (NCT00548405) in patients with active relapsing-remitting MS (RRMS) and inadequate response (≥1 relapse) to prior therapy at baseline (BL), alemtuzumab significantly increased the proportion of patients with 6-month CDI (≥1-point decrease in EDSS score) and reduced the risk of 6-month confirmed disability worsening (≥1-point EDSS increase [≥1.5-point if BL EDSS=0]), in addition to reducing the annualised relapse rate vs SC IFNB-1a over 2 years. While the EDSS is a widely used measure of disability in MS, it cannot effectively detect some contributors to disability, such as changes in short-range ambulation and upper extremity function.
Goal: To evaluate reduction in pre-existing disability over 2 years with alemtuzumab vs SC IFNB-1a in CARE-MS II using a novel, composite endpoint, CDI-plus, which includes measures of upper extremity function and short-range ambulation.
Methods: In the phase 3 CARE-MS II study, patients with RRMS received 2 courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days) or SC IFNB-1a 44 µg 3×/week. CDI-plus was assessed in patients with BL EDSS ≥2.0, and was defined as achieving ≥1-point EDSS decrease from BL, 20% improvement from BL in the 9-Hole Peg Test (9HPT), or 20% improvement in the Timed 25-Foot Walk (T25FW), confirmed over a 6-month period.
Results: A significantly higher proportion of alemtuzumab-treated patients (41%) achieved CDI-plus vs SC IFNB-1a (24%) (hazard ratio [HR] [95% CI]: 2.06 [1.41, 3.00], P=0.0002). Among the CDI components, significantly higher proportions of alemtuzumab patients achieved confirmed improvements vs SC IFNB-1a in EDSS (29% vs 13%; HR [95% CI]: 2.57 [1.57, 4.20], P=0.0002) and 9HPT (12% vs 5%; HR [95% CI]: 2.41 [1.06, 5.48], P=0.035) over 2 years. A numerically higher proportion achieved improvement in T25FW with alemtuzumab vs SC IFNB-1a (11% vs 9%; HR [95% CI]: 1.26 [0.65, 2.42], P=0.49).
Conclusions: Compared with SC IFNB-1a, a significantly greater proportion of alemtuzumab patients achieved CDI-plus. CDI-plus is a novel composite measure of disability improvement encompassing measures in addition to traditional EDSS scores, and may have utility as an adjunctive treatment outcome metric in MS.
Disclosure:
Study support: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
BS: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Pfizer, Novartis, Sanofi Genzyme, and Teva); research support (Acorda, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme).
JD: Honoraria (Biogen and Sanofi Genzyme).
GI: Speaking and/or advisory board honoraria (Almirall, Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva).
KT and AM: Employees of Sanofi Genzyme.
CP: Speaking and/or consulting (Almirall, Biogen, EMD Serono, Novartis, Sanofi Genzyme, and Teva); research support (Biogen, EMD Serono, Novartis, Sanofi Genzyme, and Teva).
Abstract: P610
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Disability is a primary contributor to the burden of multiple sclerosis (MS); one of the goals of therapy is thus to improve pre-existing disability. To date, few disease-modifying therapies have demonstrated confirmed disability improvement (CDI). In the CARE-MS II study (NCT00548405) in patients with active relapsing-remitting MS (RRMS) and inadequate response (≥1 relapse) to prior therapy at baseline (BL), alemtuzumab significantly increased the proportion of patients with 6-month CDI (≥1-point decrease in EDSS score) and reduced the risk of 6-month confirmed disability worsening (≥1-point EDSS increase [≥1.5-point if BL EDSS=0]), in addition to reducing the annualised relapse rate vs SC IFNB-1a over 2 years. While the EDSS is a widely used measure of disability in MS, it cannot effectively detect some contributors to disability, such as changes in short-range ambulation and upper extremity function.
Goal: To evaluate reduction in pre-existing disability over 2 years with alemtuzumab vs SC IFNB-1a in CARE-MS II using a novel, composite endpoint, CDI-plus, which includes measures of upper extremity function and short-range ambulation.
Methods: In the phase 3 CARE-MS II study, patients with RRMS received 2 courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days) or SC IFNB-1a 44 µg 3×/week. CDI-plus was assessed in patients with BL EDSS ≥2.0, and was defined as achieving ≥1-point EDSS decrease from BL, 20% improvement from BL in the 9-Hole Peg Test (9HPT), or 20% improvement in the Timed 25-Foot Walk (T25FW), confirmed over a 6-month period.
Results: A significantly higher proportion of alemtuzumab-treated patients (41%) achieved CDI-plus vs SC IFNB-1a (24%) (hazard ratio [HR] [95% CI]: 2.06 [1.41, 3.00], P=0.0002). Among the CDI components, significantly higher proportions of alemtuzumab patients achieved confirmed improvements vs SC IFNB-1a in EDSS (29% vs 13%; HR [95% CI]: 2.57 [1.57, 4.20], P=0.0002) and 9HPT (12% vs 5%; HR [95% CI]: 2.41 [1.06, 5.48], P=0.035) over 2 years. A numerically higher proportion achieved improvement in T25FW with alemtuzumab vs SC IFNB-1a (11% vs 9%; HR [95% CI]: 1.26 [0.65, 2.42], P=0.49).
Conclusions: Compared with SC IFNB-1a, a significantly greater proportion of alemtuzumab patients achieved CDI-plus. CDI-plus is a novel composite measure of disability improvement encompassing measures in addition to traditional EDSS scores, and may have utility as an adjunctive treatment outcome metric in MS.
Disclosure:
Study support: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
BS: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Pfizer, Novartis, Sanofi Genzyme, and Teva); research support (Acorda, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme).
JD: Honoraria (Biogen and Sanofi Genzyme).
GI: Speaking and/or advisory board honoraria (Almirall, Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva).
KT and AM: Employees of Sanofi Genzyme.
CP: Speaking and/or consulting (Almirall, Biogen, EMD Serono, Novartis, Sanofi Genzyme, and Teva); research support (Biogen, EMD Serono, Novartis, Sanofi Genzyme, and Teva).