{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:53:10Z","timestamp":1787313190943,"version":"build-2736575974"},"reference-count":22,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clin Appl Thromb Hemost"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hemophilia A and B are among the most common inherited bleeding disorders in humans with lifelong risk of spontaneous and recurrent bleeding. While prophylaxis with clotting factors has improved outcomes, challenges like inhibitor development and treatment burden persist. We aim for a comparative effectiveness between these agents and traditional therapy with this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Studies were identified through PubMed, Cochrane Central, and ClinicalTrials.gov up to May 30th, 2025. Eligible studies were double-arm RCTs comparing non-clotting factor prophylaxis (emicizumab, fitusiran, concizumab) and on-demand therapy in patients with hemophilia A or B.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Non-clotting factor prophylaxis significantly reduced the annualized bleeding rate (ABR) for all treated bleeds [\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009399, (RR\u2009=\u20090.13; 95% CI: 0.09\u20130.19),\n                      <jats:italic toggle=\"yes\">I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200963.8%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0107], spontaneous bleeds [RR\u2009=\u20090.08; 95% CI: (0.06, 0.11),\n                      <jats:italic toggle=\"yes\">I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.0%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.5933)] and joint bleeds [RR\u2009=\u20090.09; 95% CI: (0.06, 0.14), :\n                      <jats:italic toggle=\"yes\">I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200926.2%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.2468 ]. Haem-A-QoL total score improved with prophylaxis [MD\u2009=\u2009\u221211.08 [\u221216.34, \u22125.83],\n                      <jats:italic toggle=\"yes\">I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200957.5%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0949]. Prophylaxis increased the likelihood of achieving zero treated bleeds [RR\u2009=\u20094.11; 95% CI: (1.48%, 11.45%),\n                      <jats:italic toggle=\"yes\">I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200988.5%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001]. An exploratory network meta-analysis comparing fitusiran, emicizumab, and concizumab reported no statistically significant difference in the ABR for all treated bleeds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Compared to on-demand therapy, non-factor prophylactic therapies significantly reduce bleeding episodes, improve quality of life, and increase the likelihood of zero bleeds in patients with hemophilia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10760296261425039","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:15:25Z","timestamp":1773224125000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative Efficacy and Safety of Non-Clotting Factor Prophylaxis Versus. on-Demand Therapy in Hemophilia: A Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5197-444X","authenticated-orcid":false,"given":"Rehan","family":"Ishaque","sequence":"first","affiliation":[{"name":"Department of Medicine, Liaquat University of Medical Health & Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Subhan","family":"Talpur","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, United Health Service \u2013 Wilson Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4301-0441","authenticated-orcid":false,"given":"Huda","family":"Memon","sequence":"additional","affiliation":[{"name":"Rutgers University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laksh","family":"Ahuja","sequence":"additional","affiliation":[{"name":"Department of Medicine, Chandka Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8768-1943","authenticated-orcid":false,"given":"Fnu","family":"Reya","sequence":"additional","affiliation":[{"name":"Ghulam Muhammad Mahar Medical College Sukkur"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3072-1987","authenticated-orcid":false,"given":"Amna","family":"Ikram","sequence":"additional","affiliation":[{"name":"Fatima Jinnah Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0088-4041","authenticated-orcid":false,"given":"Muhammad Ahsan","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Medicine, Liaquat University of Medical Health & Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manahil","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Medicine, Karachi Medical and 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