{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:38:35Z","timestamp":1789166315237,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pediatric primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia and an increased risk of bleeding. Conventional therapies, while effective in some cases, are often limited by suboptimal response rates and significant adverse effects with prolonged use. Thrombopoietin receptor agonists (TPO-RAs), including recombinant human thrombopoietin (rhTPO), romiplostim, and eltrombopag, have emerged as promising therapeutic alternatives for pediatric ITP. However, a comprehensive comparison of their efficacy and safety profiles remains lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To conduct a systematic review and network meta-analysis to evaluate and compare the efficacy and safety of rhTPO, romiplostim, and eltrombopag in the treatment of pediatric ITP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature search was performed across PubMed, Embase, Cochrane Library, and other relevant databases. Seven randomized controlled trials (RCTs) involving a total of 375 pediatric ITP patients were included. Direct meta-analysis and Bayesian network meta-analysis were employed to assess overall response rates (ORR) and the incidence of serious adverse events (SAEs). The Surface Under the Cumulative Ranking Curve (SUCRA) was utilized to rank the interventions based on their efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Direct meta-analysis demonstrated that romiplostim (OR = 17.57, 95% CI: 4.90\u201363.03), eltrombopag (OR = 5.34, 95% CI: 2.50\u201311.39), and rhTPO (OR = 5.32, 95% CI: 2.03\u201313.96) were all significantly more effective than placebo in achieving ORR (P &amp;lt; 0.001). In terms of SAEs, romiplostim was associated with a higher risk (OR = 3.79, 95% CI: 0.66\u201321.85), whereas eltrombopag (OR = 0.68, 95% CI: 0.23\u20132.03) and rhTPO (OR = 0.28, 95% CI: 0.01\u20137.17) exhibited more favorable safety profiles. Network meta-analysis ranked romiplostim (SUCRA = 0.96) as the most efficacious intervention, followed by eltrombopag (0.52) and rhTPO (0.52). For safety, rhTPO (SUCRA = 0.78) ranked highest, followed by eltrombopag (0.66), while romiplostim (0.12) was associated with the highest risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Romiplostim exhibits superior efficacy in the management of pediatric ITP but necessitates vigilant monitoring for potential adverse effects, including bone marrow fibrosis. rhTPO, with its favorable safety profile, is particularly well-suited for acute bleeding scenarios. Eltrombopag offers a balanced combination of oral convenience and safety, making it an optimal choice for long-term therapy. Clinical decision-making should be guided by individual patient factors, including bleeding risk, treatment adherence, and drug accessibility. Future research should prioritize head-to-head comparative trials and long-term follow-up studies to further refine therapeutic strategies and optimize outcomes in pediatric ITP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1595774","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T01:23:48Z","timestamp":1749173028000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparative efficacy and safety of rhTPO, romiplostim, and eltrombopag in the treatment of pediatric primary immune thrombocytopenia: a systematic review and network meta-analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaofang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-019-03155-4","article-title":"Immune thrombocytopenia in children: consensus and controversies","volume":"87","author":"Singh","year":"2020","journal-title":"Indian J Pediatr"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2021.1903315","article-title":"Update on diagnosis and treatment of immune thrombocytopenia","volume":"14","author":"Sandal","year":"2021","journal-title":"Expert Rev Clin Pharmacol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006480","article-title":"An update on pediatric ITP: differentiating primary ITP, IPD, and PID","volume":"140","author":"Grace","year":"2022","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000599","article-title":"Treatment of primary and secondary immune thrombocytopenia","volume":"31","author":"Kado","year":"2019","journal-title":"Curr Opin Rheumatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2019.05.024","article-title":"Sequence of splenectomy and rituximab for the treatment of steroid-refractory immune thrombocytopenia: does it matter","volume":"94","author":"Hammond","year":"2019","journal-title":"Mayo Clin Proc"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1160\/TH16-12-0911","article-title":"Platelet receptors as therapeutic targets: Past, present and future","volume":"117","author":"Jamasbi","year":"2017","journal-title":"Thromb Haemost"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01553-7","article-title":"Thrombopoietin receptor agonists (TPO-RAs): drug class considerations for pharmacists","volume":"81","author":"Gilreath","year":"2021","journal-title":"Drugs"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002346","article-title":"Switching between eltrombopag and recombinant human thrombopoietin in patients with immune thrombocytopenia: an observational study","volume":"135","author":"Cai","year":"2022","journal-title":"Chin Med J (Engl)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.212845","article-title":"Thrombopoietin receptor agonists: ten years later","volume":"104","author":"Ghanima","year":"2019","journal-title":"Haematologica"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1055\/a-2247-4209","article-title":"Update on the use of thrombopoietin-receptor agonists in pediatrics","volume":"44","author":"Gebetsberger","year":"2024","journal-title":"Hamostaseologie"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017010660","article-title":"Eltrombopag for use in children with immune thrombocytopenia","volume":"2","author":"Kim","year":"2018","journal-title":"Blood Adv"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2165\/11208260-000000000-00000","article-title":"Romiplostim: a review of its use in immune thrombocytopenia","volume":"72","author":"Keating","year":"2012","journal-title":"Drugs"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2271568","DOI":"10.1080\/09537104.2023.2271568","article-title":"Efficacy and safety of high dose recombinant human thrombopoietin in the treatment of immune thrombocytopenia","volume":"34","author":"Wang","year":"2023","journal-title":"Platelets"},{"key":"B14","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1182\/blood-2010-10-313908","article-title":"A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia","volume":"118","author":"Bussel","year":"2011","journal-title":"Blood"},{"key":"B15","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/S0140-6736(16)00279-8","article-title":"Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study","volume":"388","author":"Tarantino","year":"2016","journal-title":"Lancet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-011-1172-9","article-title":"Romiplostim in children with chronic refractory ITP: randomized placebo controlled study","volume":"90","author":"Elalfy","year":"2011","journal-title":"Ann Hematol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.v205.6","article-title":"Efficacy and safety of recombinant human thrombopoietin for the treatment of chronic primary immune thrombocytopenia in children and adolescents: A multicentre, randomized, double-blind, placebo-controlled phase III trial","volume":"205","author":"Ma","year":"2024","journal-title":"Br J Haematol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)61107-2","article-title":"Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial","volume":"386","author":"Grainger","year":"2015","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00114-3","article-title":"Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study","volume":"2","author":"Bussel","year":"2015","journal-title":"Lancet Haematol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.7499\/j.issn.1008-8830.2018.07.004","article-title":"Efficacy of recombinant human thrombopoietin combined with high-dose dexamethasone in the treatment of refractory immune thrombocytopenia in children","volume":"20","author":"Lu","year":"2018","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S299591","article-title":"A review of romiplostim mechanism of action and clinical applicability","volume":"15","author":"Bussel","year":"2021","journal-title":"Drug Des Devel Ther"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S192481","article-title":"Romiplostim for the treatment of immune thrombocytopenia: spotlight on patient acceptability and ease of use","volume":"14","author":"Gilbert","year":"2020","journal-title":"Patient Prefer Adherence"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2023.2198089","article-title":"Efficacy and safety of thrombopoietin receptor agonists in children and adults with persistent and chronic immune thrombocytopenia: a meta-analysis","volume":"24","author":"Li","year":"2023","journal-title":"Expert Opin Pharmacother"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2157806","DOI":"10.1080\/09537104.2022.2157806","article-title":"Recombinant human thrombopoietin (rhTPO) of different dosing regimens for refractory\/relapsed primary immune thrombocytopenia: a multicenter, randomized controlled trial and pharmacokinetics study","volume":"34","author":"Liu","year":"2023","journal-title":"Platelets"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4274\/tjh.galenos.2020.2019.03803.1","article-title":"Outcomes of eltrombopag treatment and development of iron deficiency in children with immune thrombocytopenia in Turkey","volume":"37","author":"Koca Yozgat","year":"2020","journal-title":"Turk J Haematol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-225565","article-title":"International consensus report on the investigation and management of primary immune thrombocytopenia","volume":"115","author":"Provan","year":"2010","journal-title":"Blood"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-018-2445-z","article-title":"Chinese guidelines for treatment of adult primary immune thrombocytopenia","volume":"107","author":"Liu","year":"2018","journal-title":"Int J Hematol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1002\/ped4.12305","article-title":"Adapted guideline for the diagnosis and treatment of primary immune thrombocytopenia for Chinese children (2021)","volume":"6","year":"2022","journal-title":"Pediatr Invest"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2014.10.007","article-title":"Development of romiplostim: a novel engineered peptibody","volume":"52","author":"Yang","year":"2015","journal-title":"Semin Hematol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2359028","DOI":"10.1080\/09537104.2024.2359028","article-title":"Molecular insights on Eltrombopag: potential mitogen stimulants, angiogenesis, and therapeutic radioprotectant through TPO-R activation","volume":"35","author":"Subbarayan","year":"2024","journal-title":"Platelets"},{"key":"B31","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1186\/s12879-019-4388-2","article-title":"The effect of recombinant human thrombopoietin (rhTPO) on sepsis patients with acute severe thrombocytopenia: a study protocol for a multicentre randomised controlled trial (RESCUE trial)","volume":"19","author":"Zhou","year":"2019","journal-title":"BMC Infect Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.2019.185.issue-1","article-title":"Health-related quality of life in children with chronic immune thrombocytopenia treated with eltrombopag in the PETIT study","volume":"185","author":"Grainger","year":"2019","journal-title":"Br J Haematol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2016.03.1856","article-title":"Cost-effectiveness of eltrombopag versus romiplostim for the treatment of chronic immune thrombocytopenia in England and Wales","volume":"19","author":"Allen","year":"2016","journal-title":"Value Health"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1595774\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T01:23:50Z","timestamp":1749173030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1595774\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":33,"alternative-id":["10.3389\/fimmu.2025.1595774"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1595774","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,6]]},"article-number":"1595774"}}