Targeted therapies in immune thrombocytopenia: Current landscape and future directions

Abstract

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia resulting from both increased platelet destruction and impaired platelet production. Historically, treatment strategies have relied on broad immunosuppressive approaches, including corticosteroids, intravenous immunoglobulins, rituximab, and splenectomy. However, growing insights into the complex immunopathogenesis of ITP have revealed the involvement of multiple pathogenic mechanisms, including autoantibody-mediated platelet clearance, T-cell dysregulation, complement activation, abnormal B-cell responses, and defective megakaryopoiesis. These advances have facilitated the development of a range of targeted therapies directed at specific biological pathways involved in disease pathogenesis. Over the last decade, thrombopoietin receptor agonists (TPO-RAs), FcRn inhibitors, anti-CD38 monoclonal antibodies, spleen tyrosine kinase (SYK) inhibitors, Bruton tyrosine kinase (BTK) inhibitors, and BAFF-directed therapies have significantly expanded the therapeutic landscape of ITP. These agents offer distinct mechanisms of action and provide effective treatment options for patients with relapsed or refractory disease, while also supporting a more personalized approach to management. Emerging therapies targeting complement activation and other immune pathways may further broaden future treatment possibilities. Here we summarize the current understanding of the biological rationale underlying targeted therapies in ITP and critically discuss the available evidence from pivotal clinical trials and real-world studies. As the therapeutic armamentarium continues to expand, mechanism-based treatment strategies are expected to play an increasingly important role in optimizing patient outcomes and improving long-term disease control.