Contributions
Abstract: P927
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Alemtuzumab, a therapy for RRMS, has demonstrated a positive benefit-risk profile across clinical trials. In two phase 3 trials (CARE-MS I [NCT00530348]: treatment-naive; CARE-MS II [NCT00548405]: inadequate response to prior therapy), patients had significantly improved efficacy and quality-of-life (QoL) outcomes with alemtuzumab vs SC IFNB-1a over 2 years (y). Efficacy was maintained through 4 y in an extension (NCT00930553), in which 81% of pooled CARE-MS I/II patients remained on study from core study baseline until end of Y6 in the absence of continuous treatment. The safety profile of alemtuzumab is well known and includes the risk of autoimmune thyroid adverse events (AEs).
Aims: Examine the impact of thyroid AEs over 6 y on multiple domains of QoL, as assessed using the Functional Assessment of Multiple Sclerosis (FAMS) questionnaire, in pooled CARE-MS I/II patients.
Methods: Alemtuzumab patients received 2 treatment courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) in the core CARE-MS studies, with additional alemtuzumab courses (12 mg/day for 3 days; ≥12 months apart) as needed for disease activity or other disease-modifying therapies in the extension. QoL was assessed using the FAMS questionnaire (44 questions, divided into 6 subscales [emotional well-being, general contentment, mobility, family/social well-being, symptoms, and thinking/fatigue]). Thyroid function testing (baseline and quarterly) was done per comprehensive monitoring program.
Results: Of the 811 pooled CARE-MS I/II alemtuzumab patients, 42% had thyroid AEs, with 83% occurring in the first 2 y after the last alemtuzumab course; 95% (767/811) of patients had no serious thyroid AEs. Thyroid AE incidence peaked in Y3 (16%) and then declined. At Y6, patients with thyroid AEs showed significant improvements from core study baseline in FAMS total score (least-squares mean change from baseline [95% CI]: 4.0 [0.98, 6.92], P< 0.01), and in 4 of 6 subscales (emotional well-being: 0.9 [0.31, 1.49], P< 0.01; general contentment: 1.3 [0.65, 1.88], P< 0.0001; mobility: 0.7 (0.04; 1.27, P< 0.05; thinking/fatigue: 1.4 [0.51, 2.23], P< 0.01). FAMS-assessed QoL improvements were also observed in patients without thyroid AEs.
Conclusion: Over 6 y, thyroid AEs did not impact improvements in multiple aspects of QoL with alemtuzumab, as assessed by the MS-specific FAMS instrument. These findings further support the positive benefit-risk profile of alemtuzumab.
Disclosure: AB: Consulting fees and/or fees for non-CME services (Biogen, Mallinckrodt, Medtronic, Novartis, Sanofi, and Teva). RA: Advisory board participant and speaker (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva). ANB: Consulting fees/participated in clinical trials (Bayer, Biogen, Merck Serono, Novartis, Sanofi, and Teva). SE: Consulting and/or speaking fees (Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva). DG: Advisory board participant and/or speaker (Acorda, EMD Serono, and Genzyme). MMH: Honoraria for consulting and speaking at symposia (Acorda, Biogen, and Sanofi Genzyme). CI: Compensation for advisory board (Sanofi) and research support (Biogen, Roche, and Sanofi). VL: Honoraria for consulting and speaking at symposia (Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva, with approval by the HR-Department, Cologne General Hospital, and University of Cologne). CN: Consultant and speaking fees (Bayer-Schering Pharma, Genzyme, Merck Serono, Novartis, Roche, and Stendhal) and research support (Merck Serono, Novartis, and Roche). CP: Consulting and/or speaking fees, research, and travel grants (Actelion, Biogen, Merck, Novartis, Sanofi, and Teva). JR: Consulting fees for non-CME services (Acorda, Biogen Idec, Genzyme, Mallinckrodt, and Questcor). LS: Compensation for advisory board and speaking fees (Bayer, Biogen, Merck Serono, Novartis, Sanofi, Roche, and Teva). MT: Speaking honoraria and travel expenses for scientific meetings (Amirall, Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Roche, and Teva). LC, ND, CER, and JM: Employees of Sanofi. DR: Consulting fees (Bayer-Schering, Biogen, MedDay, Merck Serono, Novartis, Roche, Sanofi, and Teva Neuroscience) and research support (Biogen, GW Pharma, Merck Serono, Mitsubishi, Novartis, Sanofi, and Teva Neuroscience).STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.
Abstract: P927
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Alemtuzumab, a therapy for RRMS, has demonstrated a positive benefit-risk profile across clinical trials. In two phase 3 trials (CARE-MS I [NCT00530348]: treatment-naive; CARE-MS II [NCT00548405]: inadequate response to prior therapy), patients had significantly improved efficacy and quality-of-life (QoL) outcomes with alemtuzumab vs SC IFNB-1a over 2 years (y). Efficacy was maintained through 4 y in an extension (NCT00930553), in which 81% of pooled CARE-MS I/II patients remained on study from core study baseline until end of Y6 in the absence of continuous treatment. The safety profile of alemtuzumab is well known and includes the risk of autoimmune thyroid adverse events (AEs).
Aims: Examine the impact of thyroid AEs over 6 y on multiple domains of QoL, as assessed using the Functional Assessment of Multiple Sclerosis (FAMS) questionnaire, in pooled CARE-MS I/II patients.
Methods: Alemtuzumab patients received 2 treatment courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) in the core CARE-MS studies, with additional alemtuzumab courses (12 mg/day for 3 days; ≥12 months apart) as needed for disease activity or other disease-modifying therapies in the extension. QoL was assessed using the FAMS questionnaire (44 questions, divided into 6 subscales [emotional well-being, general contentment, mobility, family/social well-being, symptoms, and thinking/fatigue]). Thyroid function testing (baseline and quarterly) was done per comprehensive monitoring program.
Results: Of the 811 pooled CARE-MS I/II alemtuzumab patients, 42% had thyroid AEs, with 83% occurring in the first 2 y after the last alemtuzumab course; 95% (767/811) of patients had no serious thyroid AEs. Thyroid AE incidence peaked in Y3 (16%) and then declined. At Y6, patients with thyroid AEs showed significant improvements from core study baseline in FAMS total score (least-squares mean change from baseline [95% CI]: 4.0 [0.98, 6.92], P< 0.01), and in 4 of 6 subscales (emotional well-being: 0.9 [0.31, 1.49], P< 0.01; general contentment: 1.3 [0.65, 1.88], P< 0.0001; mobility: 0.7 (0.04; 1.27, P< 0.05; thinking/fatigue: 1.4 [0.51, 2.23], P< 0.01). FAMS-assessed QoL improvements were also observed in patients without thyroid AEs.
Conclusion: Over 6 y, thyroid AEs did not impact improvements in multiple aspects of QoL with alemtuzumab, as assessed by the MS-specific FAMS instrument. These findings further support the positive benefit-risk profile of alemtuzumab.
Disclosure: AB: Consulting fees and/or fees for non-CME services (Biogen, Mallinckrodt, Medtronic, Novartis, Sanofi, and Teva). RA: Advisory board participant and speaker (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva). ANB: Consulting fees/participated in clinical trials (Bayer, Biogen, Merck Serono, Novartis, Sanofi, and Teva). SE: Consulting and/or speaking fees (Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva). DG: Advisory board participant and/or speaker (Acorda, EMD Serono, and Genzyme). MMH: Honoraria for consulting and speaking at symposia (Acorda, Biogen, and Sanofi Genzyme). CI: Compensation for advisory board (Sanofi) and research support (Biogen, Roche, and Sanofi). VL: Honoraria for consulting and speaking at symposia (Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva, with approval by the HR-Department, Cologne General Hospital, and University of Cologne). CN: Consultant and speaking fees (Bayer-Schering Pharma, Genzyme, Merck Serono, Novartis, Roche, and Stendhal) and research support (Merck Serono, Novartis, and Roche). CP: Consulting and/or speaking fees, research, and travel grants (Actelion, Biogen, Merck, Novartis, Sanofi, and Teva). JR: Consulting fees for non-CME services (Acorda, Biogen Idec, Genzyme, Mallinckrodt, and Questcor). LS: Compensation for advisory board and speaking fees (Bayer, Biogen, Merck Serono, Novartis, Sanofi, Roche, and Teva). MT: Speaking honoraria and travel expenses for scientific meetings (Amirall, Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Roche, and Teva). LC, ND, CER, and JM: Employees of Sanofi. DR: Consulting fees (Bayer-Schering, Biogen, MedDay, Merck Serono, Novartis, Roche, Sanofi, and Teva Neuroscience) and research support (Biogen, GW Pharma, Merck Serono, Mitsubishi, Novartis, Sanofi, and Teva Neuroscience).STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.