Contributions
Abstract: P633
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is a twice daily, oral medication approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). DMF is thought to exert its effect through the activation of Nrf2. Given the immuno-modulatory properties of DMF, the effects on immune function, specifically the response to vaccinations in MS patients treated with DMF, was investigated.
Objectives: To evaluate the immune response to tetanus diphtheria toxoids vaccine (Td) and 2 other antigens in DMF-treated compared to non-pegylated interferon (IFN)-treated patients with relapsing forms of MS.
Methods: In this open-label, multicenter study (NCT02097849), patients received 3 vaccinations:
(1) Td (Tenivac®) to test the integrity of the T cell-dependent anamnestic humoral response
(2) Pneumovax® 23 (PPSV23) to assess the mostly T cell-independent humoral response, and
(3) MCV4 (Menveo®) to test the integrity of the T cell-dependent neo-antigen response.
Patients had to be treated with DMF (240 mg BID) for ≥6 months or non-pegylated IFN (with a stable, approved dose) for ≥3 months. In addition, patients had to have received a tetanus vaccination 2-15 years prior to Screening with an anti-tetanus immunoglobulin G (IgG) titer at Screening ≤1/2 the upper limit of detection. Blood samples were taken at Screening, Day 1, and Week 4. The primary endpoint was the proportion of subjects with a ≥2-fold rise in anti-tetanus serum IgG levels from pre-vaccination to 4 weeks after Td vaccination.
Results: A total of 69 patients (38 in DMF group; 33 in IFN group) were enrolled in the study. Mean age was 45 years (range: 27-55); 85.5% were female. As measured by the primary endpoint, the responder rates to Td vaccination are comparable between the DMF and IFN-treated groups. Full results of the response to the 3 different vaccinations will be presented.
Conclusions: Overall, the vaccine response to a recall antigen like Td in DMF-treated patients is comparable to that in IFN-treated patients. This study provides insights into the ability of DMF-treated patients to mount an immune response to a recall, neo-, and T-cell independent antigens.
Disclosure: Supported by: Biogen.
Christian von Hehn: employee of and holds stock/stock options in Biogen
Jonathan Howard: book contract with Demos-Springer publishing, stockholder in ReelDx.com
Shifang Liu: employee of and holds stock/stock options in Biogen
Ven Meka: employee of and holds stock/stock options in Biogen
Joe Pultz: employee of Biogen
Sarah Sheikh: employee of and holds stock/stock options in Biogen
Abstract: P633
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is a twice daily, oral medication approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). DMF is thought to exert its effect through the activation of Nrf2. Given the immuno-modulatory properties of DMF, the effects on immune function, specifically the response to vaccinations in MS patients treated with DMF, was investigated.
Objectives: To evaluate the immune response to tetanus diphtheria toxoids vaccine (Td) and 2 other antigens in DMF-treated compared to non-pegylated interferon (IFN)-treated patients with relapsing forms of MS.
Methods: In this open-label, multicenter study (NCT02097849), patients received 3 vaccinations:
(1) Td (Tenivac®) to test the integrity of the T cell-dependent anamnestic humoral response
(2) Pneumovax® 23 (PPSV23) to assess the mostly T cell-independent humoral response, and
(3) MCV4 (Menveo®) to test the integrity of the T cell-dependent neo-antigen response.
Patients had to be treated with DMF (240 mg BID) for ≥6 months or non-pegylated IFN (with a stable, approved dose) for ≥3 months. In addition, patients had to have received a tetanus vaccination 2-15 years prior to Screening with an anti-tetanus immunoglobulin G (IgG) titer at Screening ≤1/2 the upper limit of detection. Blood samples were taken at Screening, Day 1, and Week 4. The primary endpoint was the proportion of subjects with a ≥2-fold rise in anti-tetanus serum IgG levels from pre-vaccination to 4 weeks after Td vaccination.
Results: A total of 69 patients (38 in DMF group; 33 in IFN group) were enrolled in the study. Mean age was 45 years (range: 27-55); 85.5% were female. As measured by the primary endpoint, the responder rates to Td vaccination are comparable between the DMF and IFN-treated groups. Full results of the response to the 3 different vaccinations will be presented.
Conclusions: Overall, the vaccine response to a recall antigen like Td in DMF-treated patients is comparable to that in IFN-treated patients. This study provides insights into the ability of DMF-treated patients to mount an immune response to a recall, neo-, and T-cell independent antigens.
Disclosure: Supported by: Biogen.
Christian von Hehn: employee of and holds stock/stock options in Biogen
Jonathan Howard: book contract with Demos-Springer publishing, stockholder in ReelDx.com
Shifang Liu: employee of and holds stock/stock options in Biogen
Ven Meka: employee of and holds stock/stock options in Biogen
Joe Pultz: employee of Biogen
Sarah Sheikh: employee of and holds stock/stock options in Biogen