Contributions
Abstract: P1201
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Delayed-release dimethyl fumarate (DMF) has demonstrated a benefit in clinical and radiological outcome measures in clinical trials and real-world analyses. The safety profile of DMF is well-characterized, and data support a positive benefit-risk ratio. Lymphocyte decline is a known pharmacodynamic effect of DMF. Currently, limited data are available to describe post-DMF lymphocyte dynamics in patients who developed lymphopenia; additional real-world data are required.
Objectives: This study characterized lymphocyte count profiles in DMF-treated patients who developed lymphopenia and discontinued treatment with DMF.
Methods: This study included data obtained via retrospective medical record review from 5 US centers from April 2017-March 2018, combined with data sourced from the MSBase registry on 17 November 2017. Key inclusion: treated with DMF 3-24 months as per standard of care and discontinued DMF for any reason; baseline absolute lymphocyte count (ALC) >0.91x109/L, with ≥2 ALC < 0.91x109/L on-treatment, and ≥2 ALC post-DMF, 1 of which was recorded ≥90 days post-DMF. The primary endpoint was the change in ALC measurements over time.
Results: In this analysis, 33 patients met the inclusion criteria (US, 27; MSBase, 6); mean (range) age 51.4 (20-75); median (range) baseline ALC 1.6 (1.0-3.9) x109/L. Patients were treated with DMF for a median (range) 17.8 (4.8-23.9) months. Patients developed lymphopenia (first ALC < 0.91x109/L) 5.3 months (median) after initiating DMF. Median (range) ALC at discontinuation was 0.5 (0.2-1.0). The median ALC was 0.8x109/L >3 months after discontinuation of DMF. Of patients with ≥1 ALC < 0.8x109/L on treatment (n=32), the majority (78%) had ≥1 ALC ≥0.8x109/L post treatment; median time: 4.1 months after discontinuation. ALC >0.8x109/L was generally identified as the point at which physicians reinitiated DMF or another DMT in the present cohort.
Conclusions: These data suggest that among a majority of patients that experience lymphopenia during DMF treatment, meaningful lymphocyte reconstitution occurs after 3 months of treatment discontinuation. However, time to reconstitution estimates depend on visit schedule, and may be evident earlier in patients with more frequent assessments. The present observation underlines the clinical relevance of lymphocyte monitoring in MS patients treated with an immunotherapy and may be informative for clinicians when making DMF treatment decisions.
Supported by: Biogen
Disclosure: John Rose: Research Funding from National Multiple Sclerosis Society, Guthy Jackson Foundation, Western Institute for Biomedical Research, Teva Neuroscience and Biogen.
Enrique Alvarez: consulting fees from Biogen, Celgene, Genentech, Genzyme, Novartis, Teva, and TG Pharmaceuticals; research funding from Acorda, Biogen, Genentech, Novartis, and the Rocky Mountain MS Center.
Darin Okuda: received lecture fees from Acorda Therapeutics, Genentech, Genzyme, and Teva Neuroscience, consulting and advisory board fees from Celgene, EMD Serono, Genentech, Genzyme, and Novartis, and research support from Biogen.
Mark Gudesblatt: principal investigator for studies sponsored by Acorda, Adamas, Biogen, Novartis, Roche, Sanofi-Genzyme, and Teva; speaker bureaus for Biogen, EMD Serono, Novartis, Sanofi-Genzyme, and Teva; consultant for Biogen, EMD Serono, Novartis, and Sanofi-Genzyme.
Emily Riser: principal investigator for studies sponsored by Acorda, Biogen, Mallinckrodt, and Novartis; speaker bureaus for Biogen, Genzyme, Mallinckrodt, Novartis, and Teva Neuroscience.
Tim Spelman: received honoraria for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen; speaker honoraria from Novartis.
Helmut Butzkueven: Compensation for steering committee, advisory board and consultancy fees from Biogen, Merck, Roche, Novartis, Teva, Oxford Pharamgenesis; research support from Novartis, Biogen, Merck, NHMRC Australia, MS Research Australia, UK MS Trust.
Katherine Riester: employee of and holds stock/stock options in Biogen.
Fan Wu: employee of and holds stock/stock options in Biogen.
Sami Fam: employee of and holds stock/stock options in Biogen.
Catherine Miller employee of and holds stock/stock options in Biogen.
Abstract: P1201
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Delayed-release dimethyl fumarate (DMF) has demonstrated a benefit in clinical and radiological outcome measures in clinical trials and real-world analyses. The safety profile of DMF is well-characterized, and data support a positive benefit-risk ratio. Lymphocyte decline is a known pharmacodynamic effect of DMF. Currently, limited data are available to describe post-DMF lymphocyte dynamics in patients who developed lymphopenia; additional real-world data are required.
Objectives: This study characterized lymphocyte count profiles in DMF-treated patients who developed lymphopenia and discontinued treatment with DMF.
Methods: This study included data obtained via retrospective medical record review from 5 US centers from April 2017-March 2018, combined with data sourced from the MSBase registry on 17 November 2017. Key inclusion: treated with DMF 3-24 months as per standard of care and discontinued DMF for any reason; baseline absolute lymphocyte count (ALC) >0.91x109/L, with ≥2 ALC < 0.91x109/L on-treatment, and ≥2 ALC post-DMF, 1 of which was recorded ≥90 days post-DMF. The primary endpoint was the change in ALC measurements over time.
Results: In this analysis, 33 patients met the inclusion criteria (US, 27; MSBase, 6); mean (range) age 51.4 (20-75); median (range) baseline ALC 1.6 (1.0-3.9) x109/L. Patients were treated with DMF for a median (range) 17.8 (4.8-23.9) months. Patients developed lymphopenia (first ALC < 0.91x109/L) 5.3 months (median) after initiating DMF. Median (range) ALC at discontinuation was 0.5 (0.2-1.0). The median ALC was 0.8x109/L >3 months after discontinuation of DMF. Of patients with ≥1 ALC < 0.8x109/L on treatment (n=32), the majority (78%) had ≥1 ALC ≥0.8x109/L post treatment; median time: 4.1 months after discontinuation. ALC >0.8x109/L was generally identified as the point at which physicians reinitiated DMF or another DMT in the present cohort.
Conclusions: These data suggest that among a majority of patients that experience lymphopenia during DMF treatment, meaningful lymphocyte reconstitution occurs after 3 months of treatment discontinuation. However, time to reconstitution estimates depend on visit schedule, and may be evident earlier in patients with more frequent assessments. The present observation underlines the clinical relevance of lymphocyte monitoring in MS patients treated with an immunotherapy and may be informative for clinicians when making DMF treatment decisions.
Supported by: Biogen
Disclosure: John Rose: Research Funding from National Multiple Sclerosis Society, Guthy Jackson Foundation, Western Institute for Biomedical Research, Teva Neuroscience and Biogen.
Enrique Alvarez: consulting fees from Biogen, Celgene, Genentech, Genzyme, Novartis, Teva, and TG Pharmaceuticals; research funding from Acorda, Biogen, Genentech, Novartis, and the Rocky Mountain MS Center.
Darin Okuda: received lecture fees from Acorda Therapeutics, Genentech, Genzyme, and Teva Neuroscience, consulting and advisory board fees from Celgene, EMD Serono, Genentech, Genzyme, and Novartis, and research support from Biogen.
Mark Gudesblatt: principal investigator for studies sponsored by Acorda, Adamas, Biogen, Novartis, Roche, Sanofi-Genzyme, and Teva; speaker bureaus for Biogen, EMD Serono, Novartis, Sanofi-Genzyme, and Teva; consultant for Biogen, EMD Serono, Novartis, and Sanofi-Genzyme.
Emily Riser: principal investigator for studies sponsored by Acorda, Biogen, Mallinckrodt, and Novartis; speaker bureaus for Biogen, Genzyme, Mallinckrodt, Novartis, and Teva Neuroscience.
Tim Spelman: received honoraria for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen; speaker honoraria from Novartis.
Helmut Butzkueven: Compensation for steering committee, advisory board and consultancy fees from Biogen, Merck, Roche, Novartis, Teva, Oxford Pharamgenesis; research support from Novartis, Biogen, Merck, NHMRC Australia, MS Research Australia, UK MS Trust.
Katherine Riester: employee of and holds stock/stock options in Biogen.
Fan Wu: employee of and holds stock/stock options in Biogen.
Sami Fam: employee of and holds stock/stock options in Biogen.
Catherine Miller employee of and holds stock/stock options in Biogen.