Advances in replacement therapy with clotting factor (F) VIII or FIX product have contributed greatly to reducing the incidence of hemophilic arthropathy and improving quality of life (QOL) in patients with hemophilia. However, frequent intravenous administration of clotting factor products, blood access, and development of alloantibodies (inhibitors) have been important issues. Clinical studies aimed at addressing these issues have been conducted in Japan as well, including a multicenter study to determine factors involved in inhibitor development. Drug development has also progressed: several clotting factor products with extended half-life and non-clotting factor therapies have been introduced in quick succession. Anti-FIX/FX bispecific antibody in particular has a long half-life when administered subcutaneously and controls bleeding in patients with hemophilia A. Anti-antithrombin therapy and anti-TFPI monoclonal antibody products that work by rebalancing coagulation have also been developed. In addition, gene therapy has been approved for adults in U.S. and Europe, where improved vectors and codon optimization have enabled protein expression up to the near-therapeutic hemostatic range. Recent significant developments in hemophilia treatment are expected to overcome long-standing problems and further improve QOL.
"},{"@language":"ja","@value":"血友病医療において，血液凝固第VIII（IX）因子製剤の補充療法の進歩は，血友病性関節症発症を抑制させ，血友病患者のQOL向上に大きく貢献させた。しかし，製剤の頻回の静脈投与とblood access，同種抗体（インヒビター）出現は重要な課題であった。これらの克服を目指し，本邦もインヒビター発生要因に関する多施設共同研究などの臨床研究も実施されてきた。製剤開発では，半減期延長型製剤や非凝固因子治療薬が相次いで登場してきた。特に，抗第IX因子/第X因子バイスペシフィック抗体は皮下投与で長い半減期を有し，血友病A患者に出血抑制効果を示す。‘Rebalance coagulation’機序の抗アンチトロンビン製剤と抗TFPI抗体製剤も開発された。また，ベクター改良やコドン最適化により止血治療域までの蛋白発現が可能となった遺伝子治療は欧米では成人に対して承認されている。血友病医療の最近の著しい発展は，長年の課題を克服させ，さらなるQOL向上が期待される。
"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410583170580530944","@type":"Researcher","foaf:name":[{"@language":"en","@value":"NOGAMI Keiji"},{"@language":"ja","@value":"野上 恵嗣"}],"jpcoar:affiliationName":[{"@language":"ja","@value":"奈良県立医科大学 小児科"},{"@language":"en","@value":"Department of Pediatrics, Nara Medical University"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"04851439"},{"@type":"LISSN","@value":"04851439"},{"@type":"EISSN","@value":"18820824"},{"@type":"NDL_BIB_ID","@value":"000000024253"},{"@type":"ISSN","@value":"04851439"},{"@type":"NCID","@value":"AN00252940"}],"prism:publicationName":[{"@language":"en","@value":"Rinsho Ketsueki"},{"@language":"ja","@value":"臨床血液"},{"@language":"en","@value":"Rinsho Ketsueki"},{"@language":"en","@value":"Jpn. J. Clin. Hematol."},{"@language":"en","@value":"The Japanese Journal of Clinical Hematology"},{"@language":"ja","@value":"臨床血液"}],"dc:publisher":[{"@language":"en","@value":"The Japanese Society of Hematology"},{"@language":"ja","@value":"一般社団法人 日本血液学会"}],"prism:publicationDate":"2024","prism:volume":"65","prism:number":"9","prism:startingPage":"1087","prism:endingPage":"1093"},"url":[{"@id":"http://id.ndl.go.jp/bib/033752879"},{"@id":"https://ndlsearch.ndl.go.jp/books/R000000004-I033752879"},{"@id":"https://search.jamas.or.jp/link/ui/2025016420"}],"availableAt":"2024","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Hemophilia","dc:title":"Hemophilia"},{"@id":"https://cir.nii.ac.jp/all?q=Inhibitor","dc:title":"Inhibitor"},{"@id":"https://cir.nii.ac.jp/all?q=Non-clotting%20factor%20product","dc:title":"Non-clotting factor product"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20therapy","dc:title":"Gene therapy"},{"@id":"https://cir.nii.ac.jp/all?q=Hemophilia","dc:title":"Hemophilia"},{"@id":"https://cir.nii.ac.jp/all?q=Inhibitor","dc:title":"Inhibitor"},{"@id":"https://cir.nii.ac.jp/all?q=Non-clotting%20factor%20product","dc:title":"Non-clotting factor product"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20therapy","dc:title":"Gene therapy"}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:2013386498"},{"@type":"NDL_SEARCH","@value":"oai:ndlsearch.ndl.go.jp:R000000004-I033752879"},{"@type":"PUBMED","@value":"39358264"}]}