Contributions
Abstract: P690
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Efficacy of cladribine tablets 3.5mg/kg (cumulative dose given in short courses annually for 2 years) has been demonstrated in patients with early MS (ORACLE-MS) and in patients with relapsing-remitting multiple sclerosis (RRMS) in CLARITY/CLARITY Extension studies.
Objective: To evaluate the effect on B and T lymphocyte and natural killer (NK) cell profiles after the first administration of cladribine tablets in the ORACLE-MS, CLARITY and CLARITY Extension studies.
Methods: Longitudinal evaluation of peripheral blood lymphocyte subtypes was conducted for patients receiving the first course of cladribine tablets either as part of the initial 3.5mg/kg active treatment groups (ORACLE-MS and CLARITY) or the placebo switched to active treatment groups (CLARITY Extension). Lymphocytes were immunophenotyped at baseline, and Weeks 5, 13, 24 and 48. Changes in absolute cell numbers and composition of lymphocyte subtypes were evaluated.
Results: The baseline distributions of absolute lymphocyte counts (ALC) were similar across studies. Temporal profiles of CD19+ B lymphocytes and CD4+ and CD8+ T lymphocytes were generally consistent across studies. The most rapid reduction in cell numbers occurred in the CD19+ B cell compartment (approximately 75% at Week 5 in each study). Nadir for CD19+ B cells was reached at Week 13 with an 81%, 84% and 82% median reduction for patients treated with cladribine tablets in CLARITY (N=97), CLARITY Extension (N=136), and ORACLE-MS (N=41). Reconstitution of CD19+ B cells towards baseline occurred from Week 24 to 48. CD4+ and CD8+ T cells were also markedly reduced in numbers, but to a lesser degree than CD19+ B cells (at most 55% at Week 13 for CD4+ cells and 48% at Week 48 for CD8+ cells in patients treated with cladribine tablets in ORACLE-MS). Reductions in T cells were discontinuous but had not fully returned to baseline by week 48. CD16+/CD56+ NK cells were also transiently reduced with cladribine tablets; nadir occurred at Week 13 in ORACLE-MS (44% reduction), with recovery evident at Weeks 24 (29% reduction) and 48
(23% reduction).
Conclusions: Cladribine tablets achieved an early and discontinuous reduction of peripheral blood B cells with a rapid reconstitution to baseline, and a moderate and discontinuous reduction in T cell counts. Treatment with cladribine tablets is associated with early decreases in NK cells followed by rapid recovery.
Disclosure: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
OS: serves on the editorial boards of JAMA Neurology, Multiple Sclerosis Journal, and Therapeutic Advances in Neurological Disorders. He has served on data monitoring committees for Pfizer and TG Therapeutics without monetary compensation. He has advised Genzyme and Novartis, and has participated in a Teva-sponsored meeting. He currently receives grant support from Teva Pharmaceuticals and Opexa Therapeutics. He is funded by a Merit Review grant (federal award document number (FAIN) I01BX001674) from the United States (U.S.) Department of Veterans Affairs, Biomedical Laboratory Research and Development.
PS-S: has served on advisory boards for Biogen, Merck, Novartis, Teva, MedDay Pharmaceuticals, and GSK; on steering committees or independent data monitoring boards in trials sponsored by Merck, Teva, GSK, and Novartis; has received speaker honoraria from Biogen Idec, Merck Serono, Teva, Sanofi-Aventis, Genzyme, and Novartis. His department has received research support from Biogen, Merck, Teva, Novartis, Roche, and Genzyme.
GG: has received speaker honoraria and consulting fees from Abbvie, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec FivePrime, GlaxoSmithKline, GW Pharma, Merck,, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Genzyme, UCB, Vertex Pharmaceuticals, Ironwood, and Novartis; and has received research support unrelated to this study from Biogen Idec, Merck, Novartis, and Ironwood.
TL: has received consultancy fees or clinical research grants from Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer, Teva Neuroscience.
YH, DD and UB are employees of EMD Serono, USA.
Abstract: P690
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Efficacy of cladribine tablets 3.5mg/kg (cumulative dose given in short courses annually for 2 years) has been demonstrated in patients with early MS (ORACLE-MS) and in patients with relapsing-remitting multiple sclerosis (RRMS) in CLARITY/CLARITY Extension studies.
Objective: To evaluate the effect on B and T lymphocyte and natural killer (NK) cell profiles after the first administration of cladribine tablets in the ORACLE-MS, CLARITY and CLARITY Extension studies.
Methods: Longitudinal evaluation of peripheral blood lymphocyte subtypes was conducted for patients receiving the first course of cladribine tablets either as part of the initial 3.5mg/kg active treatment groups (ORACLE-MS and CLARITY) or the placebo switched to active treatment groups (CLARITY Extension). Lymphocytes were immunophenotyped at baseline, and Weeks 5, 13, 24 and 48. Changes in absolute cell numbers and composition of lymphocyte subtypes were evaluated.
Results: The baseline distributions of absolute lymphocyte counts (ALC) were similar across studies. Temporal profiles of CD19+ B lymphocytes and CD4+ and CD8+ T lymphocytes were generally consistent across studies. The most rapid reduction in cell numbers occurred in the CD19+ B cell compartment (approximately 75% at Week 5 in each study). Nadir for CD19+ B cells was reached at Week 13 with an 81%, 84% and 82% median reduction for patients treated with cladribine tablets in CLARITY (N=97), CLARITY Extension (N=136), and ORACLE-MS (N=41). Reconstitution of CD19+ B cells towards baseline occurred from Week 24 to 48. CD4+ and CD8+ T cells were also markedly reduced in numbers, but to a lesser degree than CD19+ B cells (at most 55% at Week 13 for CD4+ cells and 48% at Week 48 for CD8+ cells in patients treated with cladribine tablets in ORACLE-MS). Reductions in T cells were discontinuous but had not fully returned to baseline by week 48. CD16+/CD56+ NK cells were also transiently reduced with cladribine tablets; nadir occurred at Week 13 in ORACLE-MS (44% reduction), with recovery evident at Weeks 24 (29% reduction) and 48
(23% reduction).
Conclusions: Cladribine tablets achieved an early and discontinuous reduction of peripheral blood B cells with a rapid reconstitution to baseline, and a moderate and discontinuous reduction in T cell counts. Treatment with cladribine tablets is associated with early decreases in NK cells followed by rapid recovery.
Disclosure: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
OS: serves on the editorial boards of JAMA Neurology, Multiple Sclerosis Journal, and Therapeutic Advances in Neurological Disorders. He has served on data monitoring committees for Pfizer and TG Therapeutics without monetary compensation. He has advised Genzyme and Novartis, and has participated in a Teva-sponsored meeting. He currently receives grant support from Teva Pharmaceuticals and Opexa Therapeutics. He is funded by a Merit Review grant (federal award document number (FAIN) I01BX001674) from the United States (U.S.) Department of Veterans Affairs, Biomedical Laboratory Research and Development.
PS-S: has served on advisory boards for Biogen, Merck, Novartis, Teva, MedDay Pharmaceuticals, and GSK; on steering committees or independent data monitoring boards in trials sponsored by Merck, Teva, GSK, and Novartis; has received speaker honoraria from Biogen Idec, Merck Serono, Teva, Sanofi-Aventis, Genzyme, and Novartis. His department has received research support from Biogen, Merck, Teva, Novartis, Roche, and Genzyme.
GG: has received speaker honoraria and consulting fees from Abbvie, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec FivePrime, GlaxoSmithKline, GW Pharma, Merck,, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Genzyme, UCB, Vertex Pharmaceuticals, Ironwood, and Novartis; and has received research support unrelated to this study from Biogen Idec, Merck, Novartis, and Ironwood.
TL: has received consultancy fees or clinical research grants from Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer, Teva Neuroscience.
YH, DD and UB are employees of EMD Serono, USA.