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However, a subset of patients remains refractory to treatment or achieves only transient benefits, underscoring the need for alternative therapeutic approaches. Bruton's tyrosine kinase (BTK) inhibitors have emerged as a promising strategy for autoimmune cytopenias, including ITP, due to their ability to modulate key immune pathways. Rilzabrutinib, an oral, reversible BTK inhibitor, represents a novel therapeutic approach for ITP. Rilzabrutinib, an oral, reversible BTK inhibitor, offers a novel mechanism of action by preserving platelet aggregation while reducing macrophage\u2010mediated platelet clearance, distinguishing it from irreversible BTK inhibitors. This review provides an updated and comprehensive analysis of the Phase 1\/2 LUNA 2 trial and its long\u2010term extension, contextualizing rilzabrutinib within the broader treatment landscape. We also offer a comparative assessment of other BTK inhibitors investigated for ITP and discuss rilzabrutinib's potential positioning relative to existing therapies, including thrombopoietin receptor agonists (TPO\u2010RAs), rituximab, fostamatinib, and immunosuppressants. Results from the phase 1\/2\n                    <jats:styled-content style=\"fixed-case\">LUNA<\/jats:styled-content>\n                    2 trial and its long\u2010term extension demonstrated that Rilzabrutinib induced a durable platelet response in 40% of patients, with a median time to response of 11.5\u2009days. The treatment exhibited a favorable safety profile, with predominantly grade 1 or 2 adverse events and no significant safety concerns commonly associated with\n                    <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content>\n                    inhibitors, such as increased bleeding risk, hepatic toxicity, or cardiac arrhythmias. Preliminary data presented at\n                    <jats:styled-content style=\"fixed-case\">ASH<\/jats:styled-content>\n                    2024 from the ongoing Phase 3\n                    <jats:styled-content style=\"fixed-case\">LUNA<\/jats:styled-content>\n                    3 trial, a randomized, double\u2010blind study, further support rilzabrutinib's efficacy and long\u2010term safety. If confirmed, these findings suggest that rilzabrutinib could represent a valuable therapeutic option for patients with refractory\n                    <jats:styled-content style=\"fixed-case\">ITP<\/jats:styled-content>\n                    , addressing a critical unmet need and potentially redefining treatment paradigms.\n                  <\/jats:p>","DOI":"10.1111\/ejh.14425","type":"journal-article","created":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T21:39:06Z","timestamp":1744580346000},"page":"4-15","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Rilzabrutinib for the Treatment of Immune Thrombocytopenia"],"prefix":"10.1111","volume":"115","author":[{"given":"Caterina","family":"Labanca","sequence":"first","affiliation":[{"name":"Hematology Unit, Azienda Ospedaliera Annunziata  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica 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