Contributions
Abstract: EP1495
Type: ePoster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and a favourable benefit‐risk profile in relapsing multiple sclerosis clinical trials; mean absolute lymphocyte count (ALC) decreased by ~30% in the first yr of treatment. The impact of DMF on lymphocyte subsets is not well understood.
Objectives: Investigate the impact of DMF on ALC and CD4+ and CD8+ T-cells in pts taking DMF for ≥6 mos.
Methods: In this retrospective, observational study, longitudinal data were collected (21 Jul 2015-29 Feb 2016) via a single time point medical chart abstraction. The full data cohort will include ~490 pts. Key inclusion criteria: ≥6 mos continuous DMF use and ALC, CD4+, and CD8+ count at baseline and ≥1 subsequent time point while on DMF. Primary endpoints: change from baseline in ALC, CD4+, and CD8+ count at 6‐mo intervals within 1 yr after initiation of DMF, based on a repeated measures mixed model. Subgroup analysis based on prior natalizumab (NAT) use is reported at 6 and 12 mos. Interim data (as of 6 Nov 2015) are reported; final data will be presented.
Results: Interim data are available for 240 pts (76% female; mean age: 48 yrs). Estimated adjusted mean change from baseline in ALC was ~41% and ~47% at 6 and 12 mos (mean baseline: 2.316 x109/L). Sixty-six (28%) pts had prior NAT treatment, which was associated with increased mean baseline ALC compared with pts with no prior NAT (3.009 x109/L vs 2.053 x109/L) and greater percentage decrease in mean ALC at 6 mos (~46% vs ~32%), which stabilized thereafter. At 6 and 12 mos, mean CD4+ counts decreased by ~42% and ~47% in pts with prior NAT (mean baseline: 1.262 x109/L) and by ~32% and ~37% in pts with no prior NAT (mean baseline: 1.017 x109/L); mean CD8+ counts decreased by ~53% and ~62% (prior NAT; mean baseline: 0.666 x109/L) and by ~41% and ~50% (no prior NAT; mean baseline: 0.467 x109/L). Safety outcomes will be presented.
Conclusions: These real-world longitudinal data on ALC, CD4+, and CD8+ dynamics over the first yr of DMF treatment are generally consistent with clinical trial observations. Decrease in mean ALC correlates with decreases in mean CD4+ and CD8+ counts. Prior NAT use within 6 mos prior to initiation of DMF appears to influence the change in ALC, CD4+, and CD8+ count over the first 6 mos. These data support per-label ALC monitoring guidelines as an effective strategy to identify pts with prolonged lymphopenia over the first yr of DMF treatment.
Disclosure:
Supported by: Biogen
Guy Buckle: consultant and speaker for Biogen, EMD-Serono, Genentech, Genzyme-Sanofi, Novartis, Teva, and Mallinckrodt Pharmaceuticals; research support from Biogen.
Daniel Bandari: speakers" bureau and consultant for Biogen, Teva, Genzyme, Serono, Mallinckrodt, and Accorda; research support from Biogen, Genentech, Genzyme, and Allergan.
Jeffrey Greenstein: research support from Biogen.
Mark Gudesblatt: speakers" bureau for Teva, Biogen, Novartis, EMD Serono, and Genzyme/Sanofi; consultant for Biogen, Novartis, EMD Serono, and Genzyme/Sanofi; served as PI on studies sponsored by Biogen, Novartis, Acorda, Teva, Genzyme-Sanofi, Adamas, and Roche.
Bhupendra Khatri: compensation from Biogen, Serono, Teva, Genzyme, Novartis, Pfizer, Mallinkrodt, Terumo, Genentech, and Acorda.
Mariko Kita: speakers" bureau for Biogen; participated in advisory boards for Biogen and Novartis; served as Principal Investigator on studies sponsored by Biogen, Novartis, Acorda, and Serono.
Pavle Repovic: consultant for Biogen, Teva, EMD Serono, Genzyme/Sanofi, and Novartis; speakers" bureau of Biogen, EMD Serono, Novartis, Pfizer, and Teva; research support from Novartis.
Emily Riser: speakers" bureau for Biogen, Teva Neuroscience, Mallinckrodt, Genzyme, and Novartis; served as PI on studies sponsored by Biogen, Novartis, Mallinckrodt, and Accorda.
Bianca Weinstock-Guttman: participated in speakers" bureaus and served as a consultant for Biogen, Teva Neuroscience, EMD Serono, Novartis, Genzyme & Sanofi and Genentech; received grant/research support from the agencies listed in the previous sentence as well as Mallinckrodt Pharmaceuticals, Inc; serves in the editorial board for BMJ Neurology, Journal of International MS and CNS Drugs.
James Potts: employee of and holds stock/stock options in Biogen.
Nicholas Everage: employee of and holds stock/stock options in Biogen.
Christian von Hehn: employee of and holds stock/stock options in Biogen.
Monica Mann: employee of and holds stock/stock options in Biogen.
Abstract: EP1495
Type: ePoster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and a favourable benefit‐risk profile in relapsing multiple sclerosis clinical trials; mean absolute lymphocyte count (ALC) decreased by ~30% in the first yr of treatment. The impact of DMF on lymphocyte subsets is not well understood.
Objectives: Investigate the impact of DMF on ALC and CD4+ and CD8+ T-cells in pts taking DMF for ≥6 mos.
Methods: In this retrospective, observational study, longitudinal data were collected (21 Jul 2015-29 Feb 2016) via a single time point medical chart abstraction. The full data cohort will include ~490 pts. Key inclusion criteria: ≥6 mos continuous DMF use and ALC, CD4+, and CD8+ count at baseline and ≥1 subsequent time point while on DMF. Primary endpoints: change from baseline in ALC, CD4+, and CD8+ count at 6‐mo intervals within 1 yr after initiation of DMF, based on a repeated measures mixed model. Subgroup analysis based on prior natalizumab (NAT) use is reported at 6 and 12 mos. Interim data (as of 6 Nov 2015) are reported; final data will be presented.
Results: Interim data are available for 240 pts (76% female; mean age: 48 yrs). Estimated adjusted mean change from baseline in ALC was ~41% and ~47% at 6 and 12 mos (mean baseline: 2.316 x109/L). Sixty-six (28%) pts had prior NAT treatment, which was associated with increased mean baseline ALC compared with pts with no prior NAT (3.009 x109/L vs 2.053 x109/L) and greater percentage decrease in mean ALC at 6 mos (~46% vs ~32%), which stabilized thereafter. At 6 and 12 mos, mean CD4+ counts decreased by ~42% and ~47% in pts with prior NAT (mean baseline: 1.262 x109/L) and by ~32% and ~37% in pts with no prior NAT (mean baseline: 1.017 x109/L); mean CD8+ counts decreased by ~53% and ~62% (prior NAT; mean baseline: 0.666 x109/L) and by ~41% and ~50% (no prior NAT; mean baseline: 0.467 x109/L). Safety outcomes will be presented.
Conclusions: These real-world longitudinal data on ALC, CD4+, and CD8+ dynamics over the first yr of DMF treatment are generally consistent with clinical trial observations. Decrease in mean ALC correlates with decreases in mean CD4+ and CD8+ counts. Prior NAT use within 6 mos prior to initiation of DMF appears to influence the change in ALC, CD4+, and CD8+ count over the first 6 mos. These data support per-label ALC monitoring guidelines as an effective strategy to identify pts with prolonged lymphopenia over the first yr of DMF treatment.
Disclosure:
Supported by: Biogen
Guy Buckle: consultant and speaker for Biogen, EMD-Serono, Genentech, Genzyme-Sanofi, Novartis, Teva, and Mallinckrodt Pharmaceuticals; research support from Biogen.
Daniel Bandari: speakers" bureau and consultant for Biogen, Teva, Genzyme, Serono, Mallinckrodt, and Accorda; research support from Biogen, Genentech, Genzyme, and Allergan.
Jeffrey Greenstein: research support from Biogen.
Mark Gudesblatt: speakers" bureau for Teva, Biogen, Novartis, EMD Serono, and Genzyme/Sanofi; consultant for Biogen, Novartis, EMD Serono, and Genzyme/Sanofi; served as PI on studies sponsored by Biogen, Novartis, Acorda, Teva, Genzyme-Sanofi, Adamas, and Roche.
Bhupendra Khatri: compensation from Biogen, Serono, Teva, Genzyme, Novartis, Pfizer, Mallinkrodt, Terumo, Genentech, and Acorda.
Mariko Kita: speakers" bureau for Biogen; participated in advisory boards for Biogen and Novartis; served as Principal Investigator on studies sponsored by Biogen, Novartis, Acorda, and Serono.
Pavle Repovic: consultant for Biogen, Teva, EMD Serono, Genzyme/Sanofi, and Novartis; speakers" bureau of Biogen, EMD Serono, Novartis, Pfizer, and Teva; research support from Novartis.
Emily Riser: speakers" bureau for Biogen, Teva Neuroscience, Mallinckrodt, Genzyme, and Novartis; served as PI on studies sponsored by Biogen, Novartis, Mallinckrodt, and Accorda.
Bianca Weinstock-Guttman: participated in speakers" bureaus and served as a consultant for Biogen, Teva Neuroscience, EMD Serono, Novartis, Genzyme & Sanofi and Genentech; received grant/research support from the agencies listed in the previous sentence as well as Mallinckrodt Pharmaceuticals, Inc; serves in the editorial board for BMJ Neurology, Journal of International MS and CNS Drugs.
James Potts: employee of and holds stock/stock options in Biogen.
Nicholas Everage: employee of and holds stock/stock options in Biogen.
Christian von Hehn: employee of and holds stock/stock options in Biogen.
Monica Mann: employee of and holds stock/stock options in Biogen.