Contributions
Abstract: P559
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Teriflunomide is a disease modifying treatment approved for multiple sclerosis (MS). It inhibits reversibly dihydro-orotate dehydrogenase, a mitochondrial enzyme involved in de-novo pyrimidine biosynthesis, and down-regulates proliferation of activated lymphocytes.
Objectives: We further studied the impact of this drug on the lymphocyte profile of MS patients.
Methods: 55 patients with relapsing-remitting MS who initiated teriflunomide treatment were included in the study. We studied peripheral blood mononuclear cells obtained before and six months after treatment initiation and explored effector, memory and regulatory cells by flow cytometry. Wilcoxon matched pair tests were used to assess differences. p values below 0.05 after correction by Bonferroni test were considered as significant.
Results: When explored effector T and B cell subsets, we observed a decrease in the percentages of terminally differentiated CD4+ T cells (p=0.001) and plasmablasts (p< 0.0001) after 6 months of treatment. These results were confirmed with the total cell numbers (p< 0.0001 in both cases). When studied regulatory cells, we observed a clear increase of monocytes expressing programmed death-ligand 1 (PDL-1) (p=0.005), that was also confirmed with total cell numbers (p=0.01). It correlated negatively with all effector CD8+ T cell subsets. We also observed an increase in the percentage of CD8+ T cells (p=0.028) and monocytes (p=0.04) producing IL-10.
Conclusions: Teriflunomide induces a change in the abnormal immune response taking place in MS, with a specific reduction in effector T and B cells and an increase in regulatory cells. Particularly, this drug can produce a switch in the innate immune response to a tolerogenic profile.
Disclosure: S. Medina: Nothing to disclose. S. Sainz de la Maza: received payment for lecturing from Novartis, Biogen, Roche and Merck. N. Villarrubia: Nothing to disclose. R. Álvarez- Lafuente: received payment for lecturing or research from Merck, Biogen, Novartis, Sanofi-Genzyme, Teva and Roche. J.C. Álvarez-Cermeño: received payment for lecturing or research grants from Merck, Novartis, Biogen, Roche, Bayer, Teva, and Sanofi-Genzyme. R. Arroyo: received payment for lecturing or research grants from Merck, Teva, Sanofi-Aventis, Genzyme, Novartis, Biogen, Roche and Bayer. E. Monreal: Nothing to disclose. A. Tejeda-Velarde: Nothing to disclose. E. Rodríguez-Martín: Nothing to disclose. E. Roldán: Nothing to disclose. L. Costa-Frossard: received payment for lecturing from Novartis, Biogen, Roche, Bayer and Sanofi- Genzyme. L. M. Villar: received payment for lecturing or research grants from Merck, Novartis, Biogen, Roche and Sanofi- Genzyme.
Funding: FIS-PI15/00513 and RD16/0015/0001.
Abstract: P559
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Teriflunomide is a disease modifying treatment approved for multiple sclerosis (MS). It inhibits reversibly dihydro-orotate dehydrogenase, a mitochondrial enzyme involved in de-novo pyrimidine biosynthesis, and down-regulates proliferation of activated lymphocytes.
Objectives: We further studied the impact of this drug on the lymphocyte profile of MS patients.
Methods: 55 patients with relapsing-remitting MS who initiated teriflunomide treatment were included in the study. We studied peripheral blood mononuclear cells obtained before and six months after treatment initiation and explored effector, memory and regulatory cells by flow cytometry. Wilcoxon matched pair tests were used to assess differences. p values below 0.05 after correction by Bonferroni test were considered as significant.
Results: When explored effector T and B cell subsets, we observed a decrease in the percentages of terminally differentiated CD4+ T cells (p=0.001) and plasmablasts (p< 0.0001) after 6 months of treatment. These results were confirmed with the total cell numbers (p< 0.0001 in both cases). When studied regulatory cells, we observed a clear increase of monocytes expressing programmed death-ligand 1 (PDL-1) (p=0.005), that was also confirmed with total cell numbers (p=0.01). It correlated negatively with all effector CD8+ T cell subsets. We also observed an increase in the percentage of CD8+ T cells (p=0.028) and monocytes (p=0.04) producing IL-10.
Conclusions: Teriflunomide induces a change in the abnormal immune response taking place in MS, with a specific reduction in effector T and B cells and an increase in regulatory cells. Particularly, this drug can produce a switch in the innate immune response to a tolerogenic profile.
Disclosure: S. Medina: Nothing to disclose. S. Sainz de la Maza: received payment for lecturing from Novartis, Biogen, Roche and Merck. N. Villarrubia: Nothing to disclose. R. Álvarez- Lafuente: received payment for lecturing or research from Merck, Biogen, Novartis, Sanofi-Genzyme, Teva and Roche. J.C. Álvarez-Cermeño: received payment for lecturing or research grants from Merck, Novartis, Biogen, Roche, Bayer, Teva, and Sanofi-Genzyme. R. Arroyo: received payment for lecturing or research grants from Merck, Teva, Sanofi-Aventis, Genzyme, Novartis, Biogen, Roche and Bayer. E. Monreal: Nothing to disclose. A. Tejeda-Velarde: Nothing to disclose. E. Rodríguez-Martín: Nothing to disclose. E. Roldán: Nothing to disclose. L. Costa-Frossard: received payment for lecturing from Novartis, Biogen, Roche, Bayer and Sanofi- Genzyme. L. M. Villar: received payment for lecturing or research grants from Merck, Novartis, Biogen, Roche and Sanofi- Genzyme.
Funding: FIS-PI15/00513 and RD16/0015/0001.