[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-detail-435464-en":59,"doc-seo-435464-105":79},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":5,"data":60},{"doc_id":61,"user_id":62,"nickname":63,"user_avatar":64,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":66,"doc_content":67,"file_id":68,"file_url":69,"file_type":70,"file_size":71,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":72,"language_code":73,"site_id":74,"html_lang":73,"table_of_contents":75,"faqs":76,"seo_title":77,"seo_description":66,"update_tm":78,"read_time":24,"preview_page_count":4},435464,962090760608,"Indoniesian Boy","https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Rilzabrutinib in immune thrombocytopenia - a targeted, patient-centered alternative to conventional therapies - Letter to the Editor","Immune thrombocytopenia (ITP) is an autoimmune disorder driven by antibody-mediated platelet destruction and impaired production, leading to bleeding risk, fatigue, hospitalization, and reduced quality of life. Current first-line therapies raise platelet counts temporarily, while second-line options such as rituximab and thrombopoietin receptor agonists face relapse, refractoriness, and safety limitations. Rilzabrutinib, an oral reversible covalent BTK inhibitor, targets Fcγ receptor signaling and autoreactive immune pathways, showing favorable phase 1/2 and phase 3 LUNA3 outcomes. The letter argues rilzabrutinib may function as a disease-modifying, potentially long-term sustainable option for ITP.","Letter to the Editor  \nRilzabrutinib in immune thrombocytopenia: a targeted, patient-centered alternative to conventional therapies  \nHaris Afridi, MBBSa , Khola Qazi, MBBSb , Mariam Adnan Rizvi, MBBSb , Rida Nasir, MBBSb , Raghabendra Kumar Mahato, MBBSc ,*  \nDear Editor,  \nImmune thrombocytopenia (ITP) is an autoimmune disorder marked by antibody-mediated platelet destruction and reduced production, causing thrombocytopenia (platelet count \u003C100 × 109/L) . Patients face risks of bleeding, fatigue, hospitalization, impaired quality of life, and, rarely, fatal hemorrhage. The global prevalence is 10–23per 100 000 and incidence 2–4per 100 000person-years in both adults and children[1]. ITP is usually primary but may be secondary to drugs, autoimmune disease (e.g., systemic lupus erythematosus), malignancies (e.g., chronic lymphocytic leukemia), or infections (e.g., HIV). Autoantibodies, mainly IgG, target platelet glycoproteins (GPIIb/IIIa and GPIb/IX), promoting Fcγ receptor–mediated clearance by splenic and hepatic macrophages. They also impair thrombopoiesis through megakaryocyte apoptosis and T-cell-mediated cytotoxicity[2] . In line with the TITAN 2025 guideline on transparent and structured clinical reporting, it is essential that such insights into ITP pathogenesis and burden are communicated clearly to guide therapeutic decision-making and highlight areas needing further evaluation[3] .  \nFirst-line therapies (glucocorticoids, intravenous immunoglobulin (IVIG), and anti-D) temporarily raise counts but rarely sustain remission. Second-line options (rituximab, thrombopoietin receptor agonists) improve outcomes but are limited by relapse, refractoriness, and long-term safety concerns. Thus, novel targeted treatments are needed.  \nBruton’s tyrosine kinase (BTK) is pivotal in Fcγ receptor signaling, B-cell maturation, and antibody generation. Rilzabrutinib (PRN1008), an oral, potent, reversible covalent BTK inhibitor, offers durable inhibition with low systemic exposure and rapid  \naDepartment of Medicine, Gujranwala Medical College, Gujranwala, Pakistan, bDepartment of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan and cDepartment of Medicine, Gandaki Medical College Teaching Hospital and Research Centre, Pokhara, Nepal  \nSponsorships or competing interests that may be relevant to content are disclosed at the end of this article.  \n*Corresponding author. Address: Gandaki Medical College Teaching Hospital and Research Centre, Pokhara 33700, Nepal. Tel.: +977 9745829807.  \n[E-mail: raghabendra.mahato2024@gmcthrc.edu](E-mail: raghabendra.mahato2024@gmcthrc.edu) (R.K. Mahato).  \nCopyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This isan open access article distributed under the terms of the Creative Commons AttributionNon Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Annals of Medicine & Surgery (2026) 88:1142–1143  \nReceived 20 November 2025; Accepted 27 November 2025  \nPublished online 9 December 2025  \n[http://dx.doi.org/10.1097/MS9.0000000000004546](http://dx.doi.org/10.1097/MS9.0000000000004546)  \nclearance, minimizing off-target toxicity[4] . Unlike first-generation irreversible BTK inhibitors, it binds cysteine 481 covalently but reversibly[5], effectively suppressing downstream pathways (NF-κB, MAPK, and PI3K) and reducing autoreactive immune activation. These features position rilzabrutinib as a promising therapy for immune-mediated diseases, including ITP.  \nClinical studies show promising outcomes in several immunemediated diseases[6] . In ITP, a phase 1/2 trial demonstrated improved platelet counts in patients who were refractory to standard therapies, with a favorable safety profile. Rilzabrutinib is a first-in-class oral reversible BTK inhibitor that provides a directed therapy for ITP. Twice-","cbCaiarFCy0mq50v","https://ap.wps.com/l/cbCaiarFCy0mq50v","pdf",182226,"English","en",105,"# Immune thrombocytopenia: burden and mechanism\n# Limitations of conventional therapies\n# Rilzabrutinib: rationale and pharmacologic targeting\n# Evidence from clinical studies (phase 1/2 and LUNA3)\n# Comparative positioning versus steroids, IVIG, rituximab, and TPO-RAs","[{\"question\":\"What makes immune thrombocytopenia (ITP) clinically challenging for patients?\",\"answer\":\"ITP causes thrombocytopenia through antibody-mediated platelet destruction and reduced production, leading to bleeding risk, fatigue, hospitalization, and impaired quality of life.\"},{\"question\":\"Why are current first-line and second-line ITP therapies considered limited?\",\"answer\":\"First-line treatments such as glucocorticoids and IVIG provide only temporary platelet increases, while second-line options can be constrained by relapse, refractoriness, and long-term safety concerns.\"},{\"question\":\"How does rilzabrutinib work in ITP compared with irreversible BTK inhibitors?\",\"answer\":\"Rilzabrutinib is an oral potent reversible covalent BTK inhibitor that suppresses downstream immune pathways and reduces autoreactive activation, with lower systemic exposure and minimizing off-target toxicity.\"}]","Rilzabrutinib in immune thrombocytopenia - a targeted, patient-centered alternative to conventional therapies - Letter to the Editor | PDF",1790673750,{"code":4,"msg":80,"data":81},"ok",{"site_id":74,"language":73,"slug":82,"title":65,"keywords":83,"description":66,"schema_data":84,"social_meta":138,"head_meta":140,"extra_data":142,"updated_unix":143},"rilzabrutinib-in-immune-thrombocytopenia-a-targeted-patient-centered-alternative-to-conventional-therapies-letter-to-the-editor","",{"@graph":85,"@context":137},[86,100,120],{"@type":87,"itemListElement":88},"BreadcrumbList",[89,93,95,98],{"item":90,"name":91,"@type":92,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":94,"name":9,"@type":92,"position":14},"https://docshare.wps.com/document/",{"item":96,"name":35,"@type":92,"position":97},"https://docshare.wps.com/document/healthcare/",3,{"item":99,"name":65,"@type":92,"position":19},"https://docshare.wps.com/document/rilzabrutinib-in-immune-thrombocytopenia-a-targeted-patient-centered-alternative-to-conventional-therapies-letter-to-the-editor/435464/",{"url":99,"name":65,"@type":101,"image":102,"author":107,"headline":65,"publisher":109,"fileFormat":112,"inLanguage":73,"description":66,"dateModified":113,"datePublished":114,"encodingFormat":112,"isAccessibleForFree":115,"interactionStatistic":116},"DigitalDocument",{"url":103,"@type":104,"width":105,"height":106},"https://docshare.wps.com/thumbnails/rilzabrutinib-in-immune-thrombocytopenia-a-targeted-patient-centered-alternative-to-conventional-therapies-letter-to-the-editor/435464.png","ImageObject",300,407,{"name":63,"@type":108},"Person",{"url":90,"name":110,"@type":111},"DocShare","Organization","application/pdf","2026-10-29","2026-09-29",true,{"@type":117,"interactionType":118,"userInteractionCount":39},"InteractionCounter",{"@type":119},"ViewAction",{"@type":121,"mainEntity":122},"FAQPage",[123,129,133],{"name":124,"@type":125,"acceptedAnswer":126},"What makes immune thrombocytopenia (ITP) clinically challenging for patients?","Question",{"text":127,"@type":128},"ITP causes thrombocytopenia through antibody-mediated platelet destruction and reduced production, leading to bleeding risk, fatigue, hospitalization, and impaired quality of life.","Answer",{"name":130,"@type":125,"acceptedAnswer":131},"Why are current first-line and second-line ITP therapies considered limited?",{"text":132,"@type":128},"First-line treatments such as glucocorticoids and IVIG provide only temporary platelet increases, while second-line options can be constrained by relapse, refractoriness, and long-term safety concerns.",{"name":134,"@type":125,"acceptedAnswer":135},"How does rilzabrutinib work in ITP compared with irreversible BTK inhibitors?",{"text":136,"@type":128},"Rilzabrutinib is an oral potent reversible covalent BTK inhibitor that suppresses downstream immune pathways and reduces autoreactive activation, with lower systemic exposure and minimizing off-target toxicity.","https://schema.org",{"og:url":99,"og:type":139,"og:title":65,"og:site_name":110,"og:description":66},"article",{"robots":141,"canonical":99},"index,follow",{"doc_id":61,"site_id":74},1790734530]