Contributions
Abstract: P1273
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: Dimethyl fumarate (DMF) alters the composition of circulating immune cells and induces lymphopenia in a subpopulation of treated multiple sclerosis (MS) patients.
Objective: To investigate the relationship between the leukocyte composition in DMF-treated MS patients and their disease activity in the first year of therapy.
Methods: Peripheral blood samples from 91 relapsing-remitting MS patients were immunophenotyped using flow cytometry. The lymphocyte subset analysis included CD3+, CD4+, CD8+, CD19+ and CD56+ subpopulations. We compared untreated MS patients (n=40) with DMF-treated MS patients (n=51) 6 months after treatment onset. Disease activity of DMF-treated patients was then longitudinally assessed and defined as MRI activity and/or clinical relapse in the first year under DMF treatment (mean follow-up 11.5 months).
Results: MS patients without evidence of disease activity showed significantly lower absolute counts of total CD3+ T cells (p< 0.002), including CD4+ (p< 0.032) and CD8+ T cells (p< 0.001), as well as CD19+ B cells (p< 0.021) in comparison to MS patients with disease activity under DMF treatment. In addition, patients without disease activity demonstrated an increased CD4+/CD8+ ratio (p< 0.025) indicating a disproportionate reduction of CD8+ T cells relative to CD4+ T cells. The degree of CD8+ T cell reduction at 6 months after commencement of DMF enabled prediction of the treatment response in the first year (area under the receiver operating characteristic (ROC) curve 0.767 [0.633 - 0.901]).
Conclusion: DMF treatment response is associated with lower circulating T cells and B cells, and particularly characterized by a disproportionate reduction of CD8+ T cells. Changes in the cellular immune profiles during DMF treatment are clinically relevant and might be used to predict clinical response to DMF treatment.
Disclosure: V. Fleischer: nothing to disclose
M. Friedrich: nothing to disclose
A. Rezk: nothing to disclose
U. Bühler: nothing to disclose
E. Witsch: nothing to disclose
T. Uphaus: nothing to disclose
S. Groppa: nothing to disclose
F. Luessi has received travel grants from Teva Pharma and Merck Serono.
S. Bittner has received honoraria for lecturing, travel expenses for attending meetings, and financial research support from Bayer Schering AG, Biogen Idec, Novartis, and TEVA.
A. Bar-Or Scientific Advisory Boards: Diogenix, Advisor, Scientific Board, 2008-Ono Pharmacia, Advisor, Scientific Board, 2008-Receptos, Advisor, Scientific Board, 2011 - Roche, Advisor, Scientific Board, 2008-Novartis, Advisor, Scientific Board, 2012- GSK, Advisor 2012 - Guthy Jackson Greater Good Foundation, Scientific Advisor, 2008-
Funding for Travel or Speaker Honoraria:
Diogenix, Advisor, Scientific Board, 2008- Ono Pharmacia, Advisor, Scientific Board, 2008- Receptos, Advisor, Scientific Board, 2011 - Roche, Advisor, Scientific Board, 2008-Novartis, Advisor, Scientific Board, 2012- GSK, Advisor 2012 -
Editorial Boards:
Neurology, Editorial Board Member, 2008- Clinical and Experimental Neuroimmunology, Editorial BoardMember, 2010 -
Consultancies:
Diogenix, Advisor, Scientific Board, 2008-Ono Pharmacia, Advisor, Scientific Board, 2008-Receptos, Advisor, Scientific Board, 2011 - Roche, Advisor, Scientific Board, 2008-Novartis, Advisor, Scientific Board, 2012- GSK, Advisor 2012 -
Research Support, Commercial Entities: 1. Novartis 2. EMD Serono 3. Genzyme-Sanofi
F. Zipp has received research grants from Teva, Merck Serono, Novartis and Bayer as well as consultation fees from Teva, Merck Serono, Novartis, Bayer Healthcare, Biogen Idec Germany, ONO, Genzyme, Sanofi-Aventis and Octapharma. Her travel compensation has been provided for by the aforementioned companies.
Abstract: P1273
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: Dimethyl fumarate (DMF) alters the composition of circulating immune cells and induces lymphopenia in a subpopulation of treated multiple sclerosis (MS) patients.
Objective: To investigate the relationship between the leukocyte composition in DMF-treated MS patients and their disease activity in the first year of therapy.
Methods: Peripheral blood samples from 91 relapsing-remitting MS patients were immunophenotyped using flow cytometry. The lymphocyte subset analysis included CD3+, CD4+, CD8+, CD19+ and CD56+ subpopulations. We compared untreated MS patients (n=40) with DMF-treated MS patients (n=51) 6 months after treatment onset. Disease activity of DMF-treated patients was then longitudinally assessed and defined as MRI activity and/or clinical relapse in the first year under DMF treatment (mean follow-up 11.5 months).
Results: MS patients without evidence of disease activity showed significantly lower absolute counts of total CD3+ T cells (p< 0.002), including CD4+ (p< 0.032) and CD8+ T cells (p< 0.001), as well as CD19+ B cells (p< 0.021) in comparison to MS patients with disease activity under DMF treatment. In addition, patients without disease activity demonstrated an increased CD4+/CD8+ ratio (p< 0.025) indicating a disproportionate reduction of CD8+ T cells relative to CD4+ T cells. The degree of CD8+ T cell reduction at 6 months after commencement of DMF enabled prediction of the treatment response in the first year (area under the receiver operating characteristic (ROC) curve 0.767 [0.633 - 0.901]).
Conclusion: DMF treatment response is associated with lower circulating T cells and B cells, and particularly characterized by a disproportionate reduction of CD8+ T cells. Changes in the cellular immune profiles during DMF treatment are clinically relevant and might be used to predict clinical response to DMF treatment.
Disclosure: V. Fleischer: nothing to disclose
M. Friedrich: nothing to disclose
A. Rezk: nothing to disclose
U. Bühler: nothing to disclose
E. Witsch: nothing to disclose
T. Uphaus: nothing to disclose
S. Groppa: nothing to disclose
F. Luessi has received travel grants from Teva Pharma and Merck Serono.
S. Bittner has received honoraria for lecturing, travel expenses for attending meetings, and financial research support from Bayer Schering AG, Biogen Idec, Novartis, and TEVA.
A. Bar-Or Scientific Advisory Boards: Diogenix, Advisor, Scientific Board, 2008-Ono Pharmacia, Advisor, Scientific Board, 2008-Receptos, Advisor, Scientific Board, 2011 - Roche, Advisor, Scientific Board, 2008-Novartis, Advisor, Scientific Board, 2012- GSK, Advisor 2012 - Guthy Jackson Greater Good Foundation, Scientific Advisor, 2008-
Funding for Travel or Speaker Honoraria:
Diogenix, Advisor, Scientific Board, 2008- Ono Pharmacia, Advisor, Scientific Board, 2008- Receptos, Advisor, Scientific Board, 2011 - Roche, Advisor, Scientific Board, 2008-Novartis, Advisor, Scientific Board, 2012- GSK, Advisor 2012 -
Editorial Boards:
Neurology, Editorial Board Member, 2008- Clinical and Experimental Neuroimmunology, Editorial BoardMember, 2010 -
Consultancies:
Diogenix, Advisor, Scientific Board, 2008-Ono Pharmacia, Advisor, Scientific Board, 2008-Receptos, Advisor, Scientific Board, 2011 - Roche, Advisor, Scientific Board, 2008-Novartis, Advisor, Scientific Board, 2012- GSK, Advisor 2012 -
Research Support, Commercial Entities: 1. Novartis 2. EMD Serono 3. Genzyme-Sanofi
F. Zipp has received research grants from Teva, Merck Serono, Novartis and Bayer as well as consultation fees from Teva, Merck Serono, Novartis, Bayer Healthcare, Biogen Idec Germany, ONO, Genzyme, Sanofi-Aventis and Octapharma. Her travel compensation has been provided for by the aforementioned companies.