22 Historical aspects of B-cell depletion in SLE

double-hit' single therapies include telitacicept (an anti-BAFF and anti-APRIL agent), ianalumab (which both enhances antibody-dependent cellular cytotoxicity-mediated B-cell depletion and blocks BAFF:BAFF-R signaling), and a novel BCMA-CD19 CAR-T cell therapy that targets both BCMA and CD19. [1]2][3] Newer single hit therapies, which could be used in conjunction with standard of care, are the JAK inhibitors.These agents include upadacitinib a classic JAK 1 inhibitor, deucravacitinib a TYK2 inhibitor and baricitinib a JAK1/2 inhibitor. [4]5][6] These small molecule drugs have the advantage of being oral agents.Both these approaches offer multitarget approaches more appropriate for the heterogenous pathogenic mechanisms' characteristic of SLE.Learning Objectives At the end of this presentation participants will be able to:. Explain the limitations of traditional add-on therapeutic strategies in SLE, specifically recognizing the suboptimal response rates (40-60%) observed in randomized controlled trials, when newer agents are added to failed standard of care .Explain the evolving paradigm in SLE treatment, emphasizing the rationale for earlier, multitargeted therapeutic approaches, whether through single 'double-hit' agents or combination regimens .Identify and describe specific examples of emerging 'doublehit' single therapies for SLE, including telitacicept, ianalumab, and BCMA-CD19 CAR-T cell therapy .Discuss the role of newer oral small molecule kinase inhibitors, such as upadacitinib and deucravacitinib, as potential additions to standard of care in SLE, considering their mechanisms and current developmental status PLENARY III: B-CELL DEPLETION IN SLE -