Evolving Paradigms in the Management of Primary Immune Thrombocytopenia in Adults: From Corticosteroids to Targeted Therapies.

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia (platelet count <100 × 109/L) in the absence of another explanatory cause. Bleeding risk has traditionally anchored clinical management, yet patient-reported data show that fatigue and impaired quality of life represent an equally prominent burden of the disease and are increasingly proposed as a practical, patient-centered axis for personalizing treatment rather than as a secondary consideration. For decades, treatment relied on corticosteroids as first-line therapy, followed by a limited range of second-line options including thrombopoietin receptor agonists (TPO-RAs), rituximab, splenectomy, and, more recently, fostamatinib. Growing understanding of the immune mechanisms underlying both accelerated platelet destruction and impaired platelet production has expanded the therapeutic landscape to include mechanism-directed agents targeting Bruton tyrosine kinase, BAFF-receptor-dependent B-cell biology, the neonatal Fc receptor, and plasma-cell compartments, together with emerging clinical interest in combining agents that act on complementary mechanistic nodes. This narrative review focuses on primary ITP in adults and examines how fatigue and other patient-reported symptoms, alongside platelet counts, can inform personalized selection among established and emerging targeted therapies. Particular attention is given to distinguishing approved therapies from investigational agents by region and date, interpreting heterogeneous trial endpoints with appropriate caution, and integrating disease features, safety considerations, and patient preferences into treatment selection. Although recent phase II and III studies support the biological and clinical promise of several targeted agents, the optimal sequencing and combination of these therapies remain to be defined.