Abstract: EP1499
Type: ePoster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: This study tested the hypothesis that Gilenya treatment alters immune homeostasis in favor of an anti-inflammatory, regulatory immune phenotype. Gilenya is an FDA-approved therapy for the treatment of MS whose effects are attributed, at least in part, to limited egress of naïve and central memory lymphocytes from secondary lymphoid organs. Little is known however, about the function of the remaining circulatory cells in patients on this drug treatment. Specifically, what is the functional outcome of Gilenya treatment on the circulating myeloid mononuclear cells and residual B-cells and T-cells?
Methods: This was a single center, non-randomized, open label trial in which blood was collected from patients prior to, and following, treatment with Gilenya as standard of care for either 1, 3, 6 or 12 months. Peripheral blood mononuclear cells were assessed at each time point for their expression of markers of distinct monocyte, B-cell and T-cell sub-populations. Monocytes and B-cells were also simultaneously purified to homogeneity and the relative pro- and anti-inflammatory bias of solutes secreted following specific activation was assessed.
Results: Changes in total T-cell, B-cell and monocyte populations showed the same trends as previously published with the relative size of the monocyte population comprising ~50% of circulating mononuclear cells after 12 months of treatment. Within monocytes the ratio of alternatively activated to conventionally activated cells was significantly increased within the first month of commencing Gilenya and remained elevated through the 12 month study. Though the B-cell population as a whole was reduced on treatment, the proportion of B-cells with a regulatory phenotype increased significantly in the first month on Gilenya and continued to increase month over month. Functional analyses of the monocyte and B-cell populations showed changes consistent with a more anti-inflammatory phenotype. Correlation of secretion patterns and cell-specific phenotype with clinical assessments is ongoing.
Conclusions: Patients treated with Gilenya showed a dramatic alteration in their immune homeostasis in favor of anti-inflammatory mononuclear cell populations. The functional changes associated with these phenotypes were also consistently increased over the 12 months of study. These data describe additional immunomodulatory mechanism of action of Gilenya therapy that may be associated with clinical efficacy.
Disclosure: EEK has received investigator initiated research funding from Novartis Pharmaceuticals Corporation. GA, AL, FG, JA and KP have nothing to disclose. MB has served as a speaker, consultant or advisor for EMD Serono, Acorda, Novartis and Genentech. LA has consulted for Biogen and Genzyme and has investigator initiated grant support from Acorda and Novartis. BTL has received investigator initiated research funding from Novartis Pharmaceuticals Corporation.
Abstract: EP1499
Type: ePoster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: This study tested the hypothesis that Gilenya treatment alters immune homeostasis in favor of an anti-inflammatory, regulatory immune phenotype. Gilenya is an FDA-approved therapy for the treatment of MS whose effects are attributed, at least in part, to limited egress of naïve and central memory lymphocytes from secondary lymphoid organs. Little is known however, about the function of the remaining circulatory cells in patients on this drug treatment. Specifically, what is the functional outcome of Gilenya treatment on the circulating myeloid mononuclear cells and residual B-cells and T-cells?
Methods: This was a single center, non-randomized, open label trial in which blood was collected from patients prior to, and following, treatment with Gilenya as standard of care for either 1, 3, 6 or 12 months. Peripheral blood mononuclear cells were assessed at each time point for their expression of markers of distinct monocyte, B-cell and T-cell sub-populations. Monocytes and B-cells were also simultaneously purified to homogeneity and the relative pro- and anti-inflammatory bias of solutes secreted following specific activation was assessed.
Results: Changes in total T-cell, B-cell and monocyte populations showed the same trends as previously published with the relative size of the monocyte population comprising ~50% of circulating mononuclear cells after 12 months of treatment. Within monocytes the ratio of alternatively activated to conventionally activated cells was significantly increased within the first month of commencing Gilenya and remained elevated through the 12 month study. Though the B-cell population as a whole was reduced on treatment, the proportion of B-cells with a regulatory phenotype increased significantly in the first month on Gilenya and continued to increase month over month. Functional analyses of the monocyte and B-cell populations showed changes consistent with a more anti-inflammatory phenotype. Correlation of secretion patterns and cell-specific phenotype with clinical assessments is ongoing.
Conclusions: Patients treated with Gilenya showed a dramatic alteration in their immune homeostasis in favor of anti-inflammatory mononuclear cell populations. The functional changes associated with these phenotypes were also consistently increased over the 12 months of study. These data describe additional immunomodulatory mechanism of action of Gilenya therapy that may be associated with clinical efficacy.
Disclosure: EEK has received investigator initiated research funding from Novartis Pharmaceuticals Corporation. GA, AL, FG, JA and KP have nothing to disclose. MB has served as a speaker, consultant or advisor for EMD Serono, Acorda, Novartis and Genentech. LA has consulted for Biogen and Genzyme and has investigator initiated grant support from Acorda and Novartis. BTL has received investigator initiated research funding from Novartis Pharmaceuticals Corporation.