FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4379523361> ?p ?o ?g. }

• W4379523361 abstract "<h3>Background</h3> Dazodalibep (DAZ) is a non-antibody biologic antagonist of CD40L. In several autoimmune diseases, the CD40/CD40L pathway is activated on a variety of cell types, including T cells, B Cells, antigen-presenting cells, and activated epithelial cells. DAZ blocks costimulatory signals between T cells and CD40-expressing B cells, disrupting the development of germinal centers, pathogenic B cells, plasma cells, and autoantibodies that are hallmarks of Sjögren’s Syndrome (SS). <h3>Objectives</h3> To evaluate the impact of DAZ on blood biomarkers of B and T cell costimulation in adult SS subjects with moderate-to-high systemic disease activity. <h3>Methods</h3> This was a randomized, double-blind, placebo-controlled, crossover study to evaluate DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity, as defined by a EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score ≥ 5. Subjects were randomized 1:1 to receive intravenous DAZ 1500 mg or placebo (PBO) Q2W x 3 doses, then Q4W x 4 additional doses (Stage 1). Starting on Day 169, subjects initially randomized to DAZ received PBO Q4W x 5 doses and subjects initially randomized to PBO received DAZ Q4W x 5 doses and were then followed for 12 weeks (Stage 2). B cell subsets downstream of T cell stimulation (Ki67+CD27+ memory, CD27 high CD38 high plasmablasts, and CD11c high atypical memory cells) were assayed via FACS throughout the study period. Serum CXCL13 concentrations, a chemokine essential for GC formation produced by activated follicular T cells, and rheumatoid factor (RF) autoantibodies were also measured. <h3>Results</h3> Concomitant with DAZ-related reductions in ESSDAI observed at Stage 1, significant and rapid reductions were observed in Ki67+CD27+ memory B cells, plasmablasts, CD11c^high memory B cells, CXCL13 and RF antibodies from day 15 onwards in subjects who received DAZ as compared to PBO. In Stage 2, similar reductions were found in these biomarkers when PBO-treated subjects were transitioned to DAZ treatment. In DAZ-treated subjects who were transitioned to PBO in stage 2, these biomarkers returned to baseline values while sustained reductions were observed in ESSDAI from baseline through the duration of stage 2. <h3>Conclusion</h3> CD40-CD40L blockade with DAZ in patients with SS reduces systemic disease activity by inhibiting T and B cell costimulation, as evidenced by treatment related reductions in blood biomarkers downstream of these pathways. <h3>Acknowledgements</h3> Funded by Horizon Therapeutics. Medical writing support provided by Brendan Lujan, PhD, an employee of Horizon Therapeutics. <h3>Disclosure of Interests</h3> Michael Smith Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Nanette Mittereder Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Michele Gunsior Shareholder of: Horizon Therapeutics plc, Employee of: Former employee of Horizon Therapeutics plc, Jodi Karnell Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Fanny Legrand Consultant of: Horizon Therapeutics plc, Kenneth Der Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Claire Emson Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, William Rees Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Ilias Alevizos Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, E. William St. Clair Consultant of: Horizon Therapeutics plc, Bristol Myers Squibb, CSL Behring, Resolve Therapeutics, Sonoma Biotherapeutics, and receives royalties from UpToDate." @default.
• W4379523361 created "2023-06-07" @default.
• W4379523361 creator A5002289410 @default.
• W4379523361 creator A5011425648 @default.
• W4379523361 creator A5018841109 @default.
• W4379523361 creator A5031718088 @default.
• W4379523361 creator A5031922621 @default.
• W4379523361 creator A5042747759 @default.
• W4379523361 creator A5054267552 @default.
• W4379523361 creator A5062502639 @default.
• W4379523361 creator A5065517276 @default.
• W4379523361 creator A5081153795 @default.
• W4379523361 creator A5087231670 @default.
• W4379523361 date "2023-05-30" @default.
• W4379523361 modified "2023-10-06" @default.
• W4379523361 title "POS0815 CD40L BLOCKADE WITH DAZODALIBEP (VIB4920/HZN4920) REDUCES BLOOD BIOMARKERS OF T AND B CELL COSTIMULATION IN SUBJECTS WITH SYSTEMIC SJÖGREN’S SYNDROME" @default.
• W4379523361 doi "https://doi.org/10.1136/annrheumdis-2023-eular.881" @default.
• W4379523361 hasPublicationYear "2023" @default.
• W4379523361 type Work @default.
• W4379523361 citedByCount "0" @default.
• W4379523361 crossrefType "proceedings-article" @default.
• W4379523361 hasAuthorship W4379523361A5002289410 @default.
• W4379523361 hasAuthorship W4379523361A5011425648 @default.
• W4379523361 hasAuthorship W4379523361A5018841109 @default.
• W4379523361 hasAuthorship W4379523361A5031718088 @default.
• W4379523361 hasAuthorship W4379523361A5031922621 @default.
• W4379523361 hasAuthorship W4379523361A5042747759 @default.
• W4379523361 hasAuthorship W4379523361A5054267552 @default.
• W4379523361 hasAuthorship W4379523361A5062502639 @default.
• W4379523361 hasAuthorship W4379523361A5065517276 @default.
• W4379523361 hasAuthorship W4379523361A5081153795 @default.
• W4379523361 hasAuthorship W4379523361A5087231670 @default.
• W4379523361 hasBestOaLocation W43795233611 @default.
• W4379523361 hasConcept C126322002 @default.
• W4379523361 hasConcept C154317977 @default.
• W4379523361 hasConcept C159654299 @default.
• W4379523361 hasConcept C200180986 @default.
• W4379523361 hasConcept C202751555 @default.
• W4379523361 hasConcept C203014093 @default.
• W4379523361 hasConcept C2776090121 @default.
• W4379523361 hasConcept C2777537477 @default.
• W4379523361 hasConcept C2778453870 @default.
• W4379523361 hasConcept C39347974 @default.
• W4379523361 hasConcept C55493867 @default.
• W4379523361 hasConcept C67662055 @default.
• W4379523361 hasConcept C71924100 @default.
• W4379523361 hasConcept C86803240 @default.
• W4379523361 hasConcept C8891405 @default.
• W4379523361 hasConcept C96926380 @default.
• W4379523361 hasConceptScore W4379523361C126322002 @default.
• W4379523361 hasConceptScore W4379523361C154317977 @default.
• W4379523361 hasConceptScore W4379523361C159654299 @default.
• W4379523361 hasConceptScore W4379523361C200180986 @default.
• W4379523361 hasConceptScore W4379523361C202751555 @default.
• W4379523361 hasConceptScore W4379523361C203014093 @default.
• W4379523361 hasConceptScore W4379523361C2776090121 @default.
• W4379523361 hasConceptScore W4379523361C2777537477 @default.
• W4379523361 hasConceptScore W4379523361C2778453870 @default.
• W4379523361 hasConceptScore W4379523361C39347974 @default.
• W4379523361 hasConceptScore W4379523361C55493867 @default.
• W4379523361 hasConceptScore W4379523361C67662055 @default.
• W4379523361 hasConceptScore W4379523361C71924100 @default.
• W4379523361 hasConceptScore W4379523361C86803240 @default.
• W4379523361 hasConceptScore W4379523361C8891405 @default.
• W4379523361 hasConceptScore W4379523361C96926380 @default.
• W4379523361 hasLocation W43795233611 @default.
• W4379523361 hasOpenAccess W4379523361 @default.
• W4379523361 hasPrimaryLocation W43795233611 @default.
• W4379523361 hasRelatedWork W1601035513 @default.
• W4379523361 hasRelatedWork W174135683 @default.
• W4379523361 hasRelatedWork W1877571168 @default.
• W4379523361 hasRelatedWork W1975420246 @default.
• W4379523361 hasRelatedWork W1994031217 @default.
• W4379523361 hasRelatedWork W2007314562 @default.
• W4379523361 hasRelatedWork W207300376 @default.
• W4379523361 hasRelatedWork W2595956860 @default.
• W4379523361 hasRelatedWork W2937775576 @default.
• W4379523361 hasRelatedWork W3040048187 @default.
• W4379523361 isParatext "false" @default.
• W4379523361 isRetracted "false" @default.
• W4379523361 workType "article" @default.