Contributions
Abstract: P553
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Alemtuzumab 12 mg showed significantly improved clinical and MRI outcomes versus SC IFNB-1a over 2 years in patients with active RRMS in two phase 3 clinical trials (CARE-MS I and II; NCT00530348; NCT00548405). Alemtuzumab remained efficacious in a 4-year extension (NCT00930553), wherein patients could receive as-needed alemtuzumab retreatment or other disease-modifying therapy (DMT); 56% of patients received no additional alemtuzumab or other DMT. The selective depletion and distinct pattern of repopulation of circulating CD52-expressing T and B lymphocytes that occur after alemtuzumab treatment may account for its effect in MS.
Aims: To examine the association between lymphocyte repopulation patterns during the CARE-MS studies and clinical/MRI disease activity through 6 years.
Methods: Blood cell counts in the CARE-MS studies were carried out monthly. Lymphocytes were phenotyped by flow cytometry quarterly and at Months 1 and 13 (ie, 1 month after receiving Courses 1 and 2 of alemtuzumab, respectively), and lymphocyte counts from the CARE-MS I and II studies were pooled for analysis. Pharmacodynamic assessments included total cell counts for the following cell types: lymphocytes, CD3+/CD4+/CD8+ T cells, and CD19+ B cells, as well as subset analyses for CD4+/CD8+ T cells (naïve/memory/regulatory [Treg]) and CD19+ B cells (immature/mature/memory). Further analyses examined ratios of CD19+ (total/immature/memory) to Treg (CD4+/CD8+) cells. The relationship between lymphocyte repopulation patterns over the 2-year core studies and efficacy over 6 years (core and extension studies combined) was assessed in patients who did or did not experience relapses, 6-month confirmed disability worsening (CDW; ≥1.0-point EDSS score increase [≥1.5 points if baseline EDSS=0]), or MRI disease activity (new gadolinium-enhancing lesions or new/enlarging T2 lesions).
Results: Lymphocyte subset repopulation kinetics over 2 years did not differ in patients with or without relapses, 6-month CDW, or MRI disease activity through 6 years. No correlation was observed between any CD19+/Treg cell count ratio and relapse, CDW, or MRI disease activity.
Conclusions: Based on these analyses, lymphocyte repopulation kinetics were not associated with return of disease activity and likely cannot be used to predict need for treatment beyond Course 2.
Disclosure: HW: Consulting and/or speaking fees, and grant/research support (Bayer, Bayer-Schering Pharma, Biogen, Elan Corporation, Lilly, Lundbeck, Merck Serono, Novartis, Novo Nordisk, Sanofi, and Teva Neuroscience). DB: Speaker panels (Biogen, Genentech, Mallinckrodt, Novartis, Sanofi, Teva) and research support (Mallinckrodt, Novartis). MC: Speaking and consulting fees, and advisory honoraria (Biogen, Genzyme, and Mallinckrodt). GC: Consulting fees (Actelion, Bayer, Merck Serono, Novartis, Sanofi, and Teva) and lecture fees (Bayer, Biogen Dompé, Merck Serono, Novartis, Sanofi, Serono, Symposia International Foundation, and Teva). YM-D: Consulting fees and/or grant support (Acorda, Bayer, Biogen, Celgene, Chugai, EMD Serono, Genzyme, Novartis, Questor, and Teva Neuroscience); grant support (NIH NIAID Autoimmune Center of Excellence: UM1-AIII0557; NIH NINDO R01-NS080821). GI: Speaking and advisory fees (Almirall, Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva). HJK: Consulting and/or speaking fees (Bayer, Biogen, Celltrion, Eisai, Genzyme, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Teva-Handok, and UCB); research support (Genzyme, Merck Serono, Ministry of Science & ICT, Teva-Handok, and UCB); steering committee member (MedImmune); co-editor (Multiple Sclerosis Journal - Experimental, Translational, and Clinical); and associate editor (Journal of Clinical Neurology). SGM: Honoraria for lecturing, travel expenses for attending meetings, and financial research support (Almirall, Amicus Therapeutics Germany, Bayer, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, and ONO). GP: Speaking and advisory fees (Bayer, Biogen, EMD Serono, Genentech, Novartis, Sanofi, and Teva). BS: Research and travel grants, honoraria for expert advice on MS, and speaking fees (Biogen, Merck, Novartis, Roche, Sanofi, and Teva). CT: Honoraria for attending advisory boards and research funding (Bayer, Biogen, Novartis, and Sanofi). TZ: Consulting or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva) and grant/research support (Biogen, Novartis, Sanofi, and Teva). AJ, LC, and ND: Employees of Sanofi. BVW: Research and travel grants, honoraria for MS-expert advice, and speaking fees (Bayer-Schering, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva). STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.
Abstract: P553
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Alemtuzumab 12 mg showed significantly improved clinical and MRI outcomes versus SC IFNB-1a over 2 years in patients with active RRMS in two phase 3 clinical trials (CARE-MS I and II; NCT00530348; NCT00548405). Alemtuzumab remained efficacious in a 4-year extension (NCT00930553), wherein patients could receive as-needed alemtuzumab retreatment or other disease-modifying therapy (DMT); 56% of patients received no additional alemtuzumab or other DMT. The selective depletion and distinct pattern of repopulation of circulating CD52-expressing T and B lymphocytes that occur after alemtuzumab treatment may account for its effect in MS.
Aims: To examine the association between lymphocyte repopulation patterns during the CARE-MS studies and clinical/MRI disease activity through 6 years.
Methods: Blood cell counts in the CARE-MS studies were carried out monthly. Lymphocytes were phenotyped by flow cytometry quarterly and at Months 1 and 13 (ie, 1 month after receiving Courses 1 and 2 of alemtuzumab, respectively), and lymphocyte counts from the CARE-MS I and II studies were pooled for analysis. Pharmacodynamic assessments included total cell counts for the following cell types: lymphocytes, CD3+/CD4+/CD8+ T cells, and CD19+ B cells, as well as subset analyses for CD4+/CD8+ T cells (naïve/memory/regulatory [Treg]) and CD19+ B cells (immature/mature/memory). Further analyses examined ratios of CD19+ (total/immature/memory) to Treg (CD4+/CD8+) cells. The relationship between lymphocyte repopulation patterns over the 2-year core studies and efficacy over 6 years (core and extension studies combined) was assessed in patients who did or did not experience relapses, 6-month confirmed disability worsening (CDW; ≥1.0-point EDSS score increase [≥1.5 points if baseline EDSS=0]), or MRI disease activity (new gadolinium-enhancing lesions or new/enlarging T2 lesions).
Results: Lymphocyte subset repopulation kinetics over 2 years did not differ in patients with or without relapses, 6-month CDW, or MRI disease activity through 6 years. No correlation was observed between any CD19+/Treg cell count ratio and relapse, CDW, or MRI disease activity.
Conclusions: Based on these analyses, lymphocyte repopulation kinetics were not associated with return of disease activity and likely cannot be used to predict need for treatment beyond Course 2.
Disclosure: HW: Consulting and/or speaking fees, and grant/research support (Bayer, Bayer-Schering Pharma, Biogen, Elan Corporation, Lilly, Lundbeck, Merck Serono, Novartis, Novo Nordisk, Sanofi, and Teva Neuroscience). DB: Speaker panels (Biogen, Genentech, Mallinckrodt, Novartis, Sanofi, Teva) and research support (Mallinckrodt, Novartis). MC: Speaking and consulting fees, and advisory honoraria (Biogen, Genzyme, and Mallinckrodt). GC: Consulting fees (Actelion, Bayer, Merck Serono, Novartis, Sanofi, and Teva) and lecture fees (Bayer, Biogen Dompé, Merck Serono, Novartis, Sanofi, Serono, Symposia International Foundation, and Teva). YM-D: Consulting fees and/or grant support (Acorda, Bayer, Biogen, Celgene, Chugai, EMD Serono, Genzyme, Novartis, Questor, and Teva Neuroscience); grant support (NIH NIAID Autoimmune Center of Excellence: UM1-AIII0557; NIH NINDO R01-NS080821). GI: Speaking and advisory fees (Almirall, Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva). HJK: Consulting and/or speaking fees (Bayer, Biogen, Celltrion, Eisai, Genzyme, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Teva-Handok, and UCB); research support (Genzyme, Merck Serono, Ministry of Science & ICT, Teva-Handok, and UCB); steering committee member (MedImmune); co-editor (Multiple Sclerosis Journal - Experimental, Translational, and Clinical); and associate editor (Journal of Clinical Neurology). SGM: Honoraria for lecturing, travel expenses for attending meetings, and financial research support (Almirall, Amicus Therapeutics Germany, Bayer, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, and ONO). GP: Speaking and advisory fees (Bayer, Biogen, EMD Serono, Genentech, Novartis, Sanofi, and Teva). BS: Research and travel grants, honoraria for expert advice on MS, and speaking fees (Biogen, Merck, Novartis, Roche, Sanofi, and Teva). CT: Honoraria for attending advisory boards and research funding (Bayer, Biogen, Novartis, and Sanofi). TZ: Consulting or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva) and grant/research support (Biogen, Novartis, Sanofi, and Teva). AJ, LC, and ND: Employees of Sanofi. BVW: Research and travel grants, honoraria for MS-expert advice, and speaking fees (Bayer-Schering, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva). STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.