Contributions
Abstract: EP1656
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Alemtuzumab, approved in >65 countries for treatment of 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 (pts) had significantly improved efficacy and quality-of-life (QoL) outcomes with alemtuzumab vs SC IFNB-1a over 2 years (y). Efficacy was maintained through Y4 in an extension (NCT00930553), in which 81% of pooled CARE-MS I/II pts 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 among other the risk of autoimmune thyroid adverse events (AEs).
Aims: Examine the impact of thyroid AE occurrence on QoL outcomes over 6 y in pooled CARE-MS I/II pts.
Methods: Alemtuzumab pts received 2 treatment courses (12 mg/day; baseline 5 days; 12 months later: 3 days) in the core CARE-MS studies, with additional courses of alemtuzumab (12 mg/day; ≥12 months apart) as needed for disease activity or other disease-modifying therapies in the extension. QoL assessments: Functional Assessment of Multiple Sclerosis (FAMS); Short-Form 36-Item (SF-36) survey mental component summary (MCS) and physical component summary (PCS); EuroQol 5-dimensions (EQ-5D) visual analogue scale (VAS). Thyroid function testing (baseline and quarterly) was done per comprehensive monitoring program.
Results: Of the pooled CARE-MS I/II alemtuzumab pts (n=811), 42% had thyroid AEs over 6 years. Thyroid AE incidence peaked in Y3 (16%) and then declined. 95% (767/811) of pts had no serious thyroid AEs, and 83% of thyroid AEs occurred in the first 2 y after the last alemtuzumab course. At Y6, pts with thyroid AEs showed significant improvements from core study baseline in FAMS (least-squares mean change from baseline [95% CI], 4.0 [0.98, 6.92]; P< 0.01), SF-36 PCS (1.0 [0.08, 1.94]; P< 0.05), and EQ-5D VAS (2.1 [0.06, 4.09]; P< 0.05) scores; change in SF-36 MCS score was numerically improved but was not statistically significant (1.1 [-0.09, 2.35]). 80% and 78% of pts with thyroid AEs had stable or improved PCS and MCS, respectively, over 6 y. QoL improvements were also observed in pts without thyroid AEs.
Conclusion: Improvements in QoL were observed with alemtuzumab over 6 y, even in pts with thyroid AEs. These findings further support the favourable benefit-risk profile of alemtuzumab.
Disclosure: TZ: Consulting and/or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva) and grant/research support (Biogen, Novartis, Sanofi, and Teva). RA: Advisory board participant and speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva). AB: Consulting fees (Biogen and Genzyme) and lectures fees (Biogen, Merck, Novartis, Roche, Sanofi, and Teva). EC: Advisory boards and/or speaker honoraria (Biogen, Merck, Roche, Novartis, Genzyme, and Teva) and unrestricted research grants (Novartis and Genzyme). GC: Consulting fees (Actelion, Bayer-Schering, Merck Serono, Novartis, Sanofi, and Teva) and lecture fees (Bayer-Schering, Biogen Dompé, Merck Serono, Novartis, Sanofi, Serono Symposia International Foundation, and Teva). EH: Honoraria and grant support (Actelion, Biogen, Merck Serono, Novartis, Receptos, Roche, Sanofi, and Teva) and supported by Ministry of Education of Czech Republic. WDH: Speaker honoraria, consultant fees, and/or participation in clinical trials (Actelion, Alkermes, Biogen Idec, Celgene, EMD Serono, Mallinckrodt, MedImmune, Novartis, Roche, Sanofi, and Teva). GI: Speaking and advisory fees (Almirall, Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva). BK: Consulting and/or speaking fees (Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi, and Teva). TM: Speaking and/or consulting fees (Allergan, Amgen, Biogen, Genentech, Genzyme, Mallinckrodt, Novartis, Sanofi-Aventis and Teva); grant/research support (Alder, Allergan, Biogen, Eli Lilly, EMD Serono, Genentech, Genzyme, Mallinckrodt, Novartis, Sanofi-Aventis, TEVA, and TG Therapeutics). DM: Speaking and/or consulting fees (Amgen, Eli Lily, Genesis Pharma, Novartis, Roche, Sanofi Genzyme, and Teva) and grant research support (Biogen and Sanofi Genzyme). PAS: Consulting and/or speaking fees (Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Novo Nordisk, Sanofi Genzyme, Servier, and Valeant) and grant research support (Novo Nordisk, Prometric, and Servier). BAS: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Pfizer, Novartis, Sanofi, and Teva) and research support (Acorda, Alkermes, Biogen, MedImmune, Novartis, Roche, and Sanofi). LC, ND, CER, and JM: Employees of Sanofi. SFH: Consulting agreements, speaker honoraria, and grant/research financial support (AbbVie, Acorda, Actelion, ADAMAS, Avanir, Bayer, Biogen Idec, Novartis, Osmotica, Questcor, Roche, Sanofi, Synthon, and Teva). STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.
Abstract: EP1656
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Alemtuzumab, approved in >65 countries for treatment of 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 (pts) had significantly improved efficacy and quality-of-life (QoL) outcomes with alemtuzumab vs SC IFNB-1a over 2 years (y). Efficacy was maintained through Y4 in an extension (NCT00930553), in which 81% of pooled CARE-MS I/II pts 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 among other the risk of autoimmune thyroid adverse events (AEs).
Aims: Examine the impact of thyroid AE occurrence on QoL outcomes over 6 y in pooled CARE-MS I/II pts.
Methods: Alemtuzumab pts received 2 treatment courses (12 mg/day; baseline 5 days; 12 months later: 3 days) in the core CARE-MS studies, with additional courses of alemtuzumab (12 mg/day; ≥12 months apart) as needed for disease activity or other disease-modifying therapies in the extension. QoL assessments: Functional Assessment of Multiple Sclerosis (FAMS); Short-Form 36-Item (SF-36) survey mental component summary (MCS) and physical component summary (PCS); EuroQol 5-dimensions (EQ-5D) visual analogue scale (VAS). Thyroid function testing (baseline and quarterly) was done per comprehensive monitoring program.
Results: Of the pooled CARE-MS I/II alemtuzumab pts (n=811), 42% had thyroid AEs over 6 years. Thyroid AE incidence peaked in Y3 (16%) and then declined. 95% (767/811) of pts had no serious thyroid AEs, and 83% of thyroid AEs occurred in the first 2 y after the last alemtuzumab course. At Y6, pts with thyroid AEs showed significant improvements from core study baseline in FAMS (least-squares mean change from baseline [95% CI], 4.0 [0.98, 6.92]; P< 0.01), SF-36 PCS (1.0 [0.08, 1.94]; P< 0.05), and EQ-5D VAS (2.1 [0.06, 4.09]; P< 0.05) scores; change in SF-36 MCS score was numerically improved but was not statistically significant (1.1 [-0.09, 2.35]). 80% and 78% of pts with thyroid AEs had stable or improved PCS and MCS, respectively, over 6 y. QoL improvements were also observed in pts without thyroid AEs.
Conclusion: Improvements in QoL were observed with alemtuzumab over 6 y, even in pts with thyroid AEs. These findings further support the favourable benefit-risk profile of alemtuzumab.
Disclosure: TZ: Consulting and/or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva) and grant/research support (Biogen, Novartis, Sanofi, and Teva). RA: Advisory board participant and speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva). AB: Consulting fees (Biogen and Genzyme) and lectures fees (Biogen, Merck, Novartis, Roche, Sanofi, and Teva). EC: Advisory boards and/or speaker honoraria (Biogen, Merck, Roche, Novartis, Genzyme, and Teva) and unrestricted research grants (Novartis and Genzyme). GC: Consulting fees (Actelion, Bayer-Schering, Merck Serono, Novartis, Sanofi, and Teva) and lecture fees (Bayer-Schering, Biogen Dompé, Merck Serono, Novartis, Sanofi, Serono Symposia International Foundation, and Teva). EH: Honoraria and grant support (Actelion, Biogen, Merck Serono, Novartis, Receptos, Roche, Sanofi, and Teva) and supported by Ministry of Education of Czech Republic. WDH: Speaker honoraria, consultant fees, and/or participation in clinical trials (Actelion, Alkermes, Biogen Idec, Celgene, EMD Serono, Mallinckrodt, MedImmune, Novartis, Roche, Sanofi, and Teva). GI: Speaking and advisory fees (Almirall, Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva). BK: Consulting and/or speaking fees (Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi, and Teva). TM: Speaking and/or consulting fees (Allergan, Amgen, Biogen, Genentech, Genzyme, Mallinckrodt, Novartis, Sanofi-Aventis and Teva); grant/research support (Alder, Allergan, Biogen, Eli Lilly, EMD Serono, Genentech, Genzyme, Mallinckrodt, Novartis, Sanofi-Aventis, TEVA, and TG Therapeutics). DM: Speaking and/or consulting fees (Amgen, Eli Lily, Genesis Pharma, Novartis, Roche, Sanofi Genzyme, and Teva) and grant research support (Biogen and Sanofi Genzyme). PAS: Consulting and/or speaking fees (Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Novo Nordisk, Sanofi Genzyme, Servier, and Valeant) and grant research support (Novo Nordisk, Prometric, and Servier). BAS: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Pfizer, Novartis, Sanofi, and Teva) and research support (Acorda, Alkermes, Biogen, MedImmune, Novartis, Roche, and Sanofi). LC, ND, CER, and JM: Employees of Sanofi. SFH: Consulting agreements, speaker honoraria, and grant/research financial support (AbbVie, Acorda, Actelion, ADAMAS, Avanir, Bayer, Biogen Idec, Novartis, Osmotica, Questcor, Roche, Sanofi, Synthon, and Teva). STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.