Emerging targeted therapies for primary immune thrombocytopenia: novel agents, combination strategies, and future directions

Abstract

An autoimmune disease with notable clinical variability, primary immune thrombocytopenia is typified by immune-mediated platelet underproduction and destruction. Conventional therapies, including glucocorticoids and splenectomy, are limited by adverse effects, high relapse rates, and surgical risks. Recently, with the in-depth study of immune thrombocytopenia, new targeted drugs have emerged rapidly. We conducted a systematic literature search of PubMed, Web of Science, and ClinicalTrials.gov from May 2010 up to May 2026, using search terms related to “immune thrombocytopenia” AND “targeted therapy” OR “novel agents.” Eligible studies included phase I–III clinical trials, prospective observational studies, and high-quality preclinical mechanistic studies evaluating novel ITP therapeutics, while case reports and editorials were excluded. Two independent reviewers screened titles and abstracts, followed by full-text assessment, with discrepancies resolved by consensus. Given the heterogeneous nature of the included evidence, we adopted a narrative synthesis approach, complemented by a clinical evidence-grading framework that stratified emerging agents by the maturity of their supporting data (phase I, phase II, phase III, or preclinical studies), rather than performing a quantitative meta-analysis. This article analyses recent therapeutic trials with Bruton’s tyrosine kinase inhibitors, splenic tyrosine kinase inhibitors, and neonatal Fc receptor antagonists, demonstrating an improvement in platelet counts and patients’ quality of life. Furthermore, combination therapy regimens show great promise in terms of synergistic effects, while cellular therapies, such as chimeric antigen receptor T-cell immunotherapy and mesenchymal stem cell therapy, appear to offer new treatment concepts for patients with persistent, chronic, refractory, or multi-refractory ITP. However, there are still many problems and shortcomings in the diagnosis and treatment of immune thrombocytopenia. In addition, the transition from preliminary evidence to routine clinical application requires larger phase III confirmatory studies, validated biomarker-driven patient selection, and context-adapted treatment algorithms that address resource-limited settings. Future research should prioritize head-to-head comparisons, combination regimens, and real-world effectiveness studies to optimize long-term outcomes for all ITP patients.