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Abstract Details

Immunomodulatory Effects of DMF Treatment on the Peripheral Lymphocyte Compartment: A Focus on Older MS Patients
Multiple Sclerosis
P6 - Poster Session 6 (12:00 PM-1:00 PM)
9-011

Treatment with DMF, an oral therapy approved for relapsing forms of multiple sclerosis (RMS), leads to pleiotropic immune changes, which are not well-described in older patients.

Describe the impact of delayed-release dimethyl fumarate (DMF) treatment over 2 years on the immune cell compartment in patients < and ≥50 years old.

PROCLAIM (EudraCT 20015-001973-42) is an open-label, 96-week (W96) study of patients aged 18-65 years with RMS (N=218) treated with DMF 240mg twice-daily. Absolute lymphocyte count (ALC) and lymphocyte subset changes were assessed longitudinally by complete blood count and flow cytometry, respectively. The relationship between age and peripheral immune cell compartments changes after DMF treatment was evaluated.

The mean (SD) age was 42 (11) years; 59/218 (27%) patients were ≥50 years old. Baseline CD4+ T cell compartment composition was similar for patients <50 and ≥50 (38% vs 36% naïve, 42% vs 44% central memory, 19% vs 19% effector memory) but differed among the CD8+ T cells (39% vs 28% naïve, 12% vs 18% central memory, and 20% vs 25% effector memory). Regardless of age, relative proportion of naïve CD4+ and CD8+ T cells increased and central and effector memory CD4+ and CD8+ T cells decreased at W96. Similarly, from baseline to W96, relative proportion of naïve B cells increased <50 and ≥50 (baseline: 63% vs 68%, W96 75% vs 80%) and transitional B cells increased (baseline: 5% vs 4%, W96 11% vs 12%). SAE incidence was similar, 13% (<50) vs 10% (≥50).

Immune cell changes with DMF treatment were similar in patients <50 to ≥50 years old apart from the CD8+ compartment where age impacted the proportion of naïve and activated cells. Otherwise, for all age groups, memory populations were selectively reduced, while the naïve compartment increased. SAEs did not increase with age.

Support: Biogen

Authors/Disclosures
Fabrizio Giuliani, MD (University of Alberta)
PRESENTER
No disclosure on file
Erin Longbrake, MD, PhD, FAAN (Yale University) Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Longbrake has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Longbrake has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Longbrake has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Longbrake has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ACTRIMS. Dr. Longbrake has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of Neurology. The institution of Dr. Longbrake has received research support from Genentech. The institution of Dr. Longbrake has received research support from Race to Erase MS. The institution of Dr. Longbrake has received research support from NINDS K23. The institution of Dr. Longbrake has received research support from Robert Patterson Leet Trust. The institution of Dr. Longbrake has received research support from Biogen. The institution of Dr. Longbrake has received research support from National MS Society. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with Department of Defense (CDMRP). Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Programmatic Review with Department of Defense (CDMRP). Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with National Institute of Health .
Yang Mao-Draayer, MD (University of Michigan, Department of Neurology) Dr. Mao-Draayer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen Idec. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme-Sanofi. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Mao-Draayer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizone . Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme-Sanofi. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizone. Dr. Mao-Draayer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen Idec. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. The institution of Dr. Mao-Draayer has received research support from NIH . The institution of Dr. Mao-Draayer has received research support from Genzyme-Sanofi. The institution of Dr. Mao-Draayer has received research support from Novartis. The institution of Dr. Mao-Draayer has received research support from Genentech.
Derrick Robertson, MD Dr. Robertson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Greenwich Biosciences. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Janssen. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi Genzyme. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. Dr. Robertson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mallinckrodt. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Robertson has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Robertson has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Genentech. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for PRIME CME. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Janssen. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Horizon. Dr. Robertson has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for TG Therapeutics. Dr. Robertson has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for McVeigh. Dr. Robertson has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Mccumber. Dr. Robertson has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Goodis. The institution of Dr. Robertson has received research support from Biogen. The institution of Dr. Robertson has received research support from EMD Serono. The institution of Dr. Robertson has received research support from Jansenn. The institution of Dr. Robertson has received research support from Genentech. The institution of Dr. Robertson has received research support from Patient-Centered Outcomes Research Institute. The institution of Dr. Robertson has received research support from Novartis. The institution of Dr. Robertson has received research support from Sanofi Genzyme. The institution of Dr. Robertson has received research support from TG Therapeutics. The institution of Dr. Robertson has received research support from Prime. The institution of Dr. Robertson has received research support from Greenwich Biosciences. The institution of Dr. Robertson has received research support from Atara Biotherapeutics. The institution of Dr. Robertson has received research support from CorEvitas. The institution of Dr. Robertson has received research support from Anokion. Dr. Robertson has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Consortium of Multiple Sclerosis Centers. Dr. Robertson has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Multiple Sclerosis Association of America.
Amit Bar-Or, MD, FRCPC (University of Pennsylvania) Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen/Actelion. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atara Biotherapeutics. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech. The institution of Dr. Bar-Or has received research support from Merck/EMD Serono.
Oksana Mokliatchouk Oksana Mokliatchouk has received personal compensation for serving as an employee of Biogen. Oksana Mokliatchouk has received stock or an ownership interest from Biogen.
Eris Bame No disclosure on file
Dongxia Xing No disclosure on file
Becky J. Parks, MD (Blueprint Medicines) Dr. Parks has received personal compensation for serving as an employee of Alexion Pharmaceuticals. An immediate family member of Dr. Parks has received personal compensation for serving as an employee of Massachusetts General Hospital. Dr. Parks has stock in Biogen. Dr. Parks has stock in Illumina. An immediate family member of Dr. Parks has stock in Regeneron. Dr. Parks has stock in Blueprint Medicines. Dr. Parks has stock in Sanofi. An immediate family member of Dr. Parks has stock in Vertex. Dr. Parks has stock in AstraZeneca. The institution of an immediate family member of Dr. Parks has received research support from NIH/NCI. The institution of an immediate family member of Dr. Parks has received research support from Leukemia & Lymphoma Society. The institution of an immediate family member of Dr. Parks has received research support from AstraZeneca Scholar Award.
Chongshu Chen Chongshu Chen has received personal compensation for serving as an employee of Alnylam Pharmaceuticals. Chongshu Chen has stock in Alnylam Pharmaceuticals.
Catherine Miller Catherine Miller has received personal compensation for serving as an employee of Biogen. Catherine Miller has received stock or an ownership interest from Biogen.