Contributions
Abstract: P701
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Teriflunomide, a drug approved for treatment of relapsing-remitting multiple sclerosis (MS) acts on highly proliferating cells, such as activated lymphocytes, inhibiting enzyme dihydroorotate dehydrogenase, involved in de novo pyrimidine biosynthesis, without impacting on protective immunity. Clinical trials in MS showed that teriflunomide can cause a mean decrease in leukocyte counts of approximately 15 % during the first months of treatment, but its effect on immune cell subpopulations is not clearly understood. We have therefore studied the immunomodulatory effect of this drug on innate and adaptive immune cell populations. Blood lymphocytes were isolated from 10 MS patients before and after 3 or 12 months of treatment. Adaptive and innate immune cell subsets were analyzed by flow cytometry, as follows: B cells (memory, regulatory and mature subsets), T cells (effector and regulatory subsets) and natural killer (NK) cells (CD56dim and CD56bright subsets). Our results show that teriflunomide impacts B-cell subsets, significantly reducing absolute counts of total CD19+ B cells, and mature and regulatory B-cell subsets. T cells were affected to a lesser extent, with a trend in reduction of absolute counts for both T effector CD4+ cells (Th1, Th17 and Th1/17) and T regulatory CD8+ and CD4+ cells. Teriflunomide had no detectable impact on NK-cell numbers. In conclusion our data showed that, in a small studied cohort of patients, teriflunomide treatment impacts mainly and significantly on B-cell numbers, while having a milder effect on T-cell numbers. Larger cohorts are necessary to confirm these findings and understand the impact of teriflunomide on the functionality of these cells.
Disclosure: F. Ivaldi, N. Kerlero de Rosbo, F. Benvenuto have no conflict of interest to disclose. I. Gandoglia has received funding for travel from Biogen Idec, Novartis, and Genzyme and honoraria from Amirall. A. Laroni has received consulting honoraria and/or speaker fees from Novartis, Genzyme, Biogen, Merck-Serono and Teva. G. Mancardi has received honoraria, travel expenses, and financial support for research from Biogen Idec, Bayer Schering, Sanofi Aventis, Teva, Merck Serono and Novartis. A. Uccelli has received consulting honoraria and/or speaker fees from Genentech, Roche, Biogen, Genzyme, Teva, Novartis and Merck-Serono. CS has served on advisory boards of Biogen Idec, Merck Serono. He received speaking honoraria from Bayer Schering, Biogen Idec, Merck Serono, Almirall, Teva, and Genzyme.
Abstract: P701
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Teriflunomide, a drug approved for treatment of relapsing-remitting multiple sclerosis (MS) acts on highly proliferating cells, such as activated lymphocytes, inhibiting enzyme dihydroorotate dehydrogenase, involved in de novo pyrimidine biosynthesis, without impacting on protective immunity. Clinical trials in MS showed that teriflunomide can cause a mean decrease in leukocyte counts of approximately 15 % during the first months of treatment, but its effect on immune cell subpopulations is not clearly understood. We have therefore studied the immunomodulatory effect of this drug on innate and adaptive immune cell populations. Blood lymphocytes were isolated from 10 MS patients before and after 3 or 12 months of treatment. Adaptive and innate immune cell subsets were analyzed by flow cytometry, as follows: B cells (memory, regulatory and mature subsets), T cells (effector and regulatory subsets) and natural killer (NK) cells (CD56dim and CD56bright subsets). Our results show that teriflunomide impacts B-cell subsets, significantly reducing absolute counts of total CD19+ B cells, and mature and regulatory B-cell subsets. T cells were affected to a lesser extent, with a trend in reduction of absolute counts for both T effector CD4+ cells (Th1, Th17 and Th1/17) and T regulatory CD8+ and CD4+ cells. Teriflunomide had no detectable impact on NK-cell numbers. In conclusion our data showed that, in a small studied cohort of patients, teriflunomide treatment impacts mainly and significantly on B-cell numbers, while having a milder effect on T-cell numbers. Larger cohorts are necessary to confirm these findings and understand the impact of teriflunomide on the functionality of these cells.
Disclosure: F. Ivaldi, N. Kerlero de Rosbo, F. Benvenuto have no conflict of interest to disclose. I. Gandoglia has received funding for travel from Biogen Idec, Novartis, and Genzyme and honoraria from Amirall. A. Laroni has received consulting honoraria and/or speaker fees from Novartis, Genzyme, Biogen, Merck-Serono and Teva. G. Mancardi has received honoraria, travel expenses, and financial support for research from Biogen Idec, Bayer Schering, Sanofi Aventis, Teva, Merck Serono and Novartis. A. Uccelli has received consulting honoraria and/or speaker fees from Genentech, Roche, Biogen, Genzyme, Teva, Novartis and Merck-Serono. CS has served on advisory boards of Biogen Idec, Merck Serono. He received speaking honoraria from Bayer Schering, Biogen Idec, Merck Serono, Almirall, Teva, and Genzyme.