{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:28:50Z","timestamp":1782991730211,"version":"3.54.5"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The thrombopoietin receptor agonist (TPO-RA) romiplostim has been shown to be efficacious in the treatment of aplastic anemia (AA) refractory to immunosuppressive therapy. However, there are few reports on predictors of TPO-RA efficacy. We analyzed patient clinical and baseline laboratory data from two clinical trials that enrolled patients with refractory AA, a phase 2 dose-finding study (NCT02094417) and a phase 2\/3 study (NCT02773290), to determine predictors of romiplostim efficacy. Data from 66 patients (35 from the phase 2 dose-finding study and 31 from the phase 2\/3 study), median age 47.0 (range 20\u201378) years, were analyzed. Of these, 51.5% (34\/66) had non-severe AA, 86.4% (57\/66) had received prior therapy with anti-thymocyte globulin plus cyclosporine, and 80.3% (53\/66) were transfusion-dependent. At 27\u00a0weeks, no patients achieved a complete response, 57.4% (35\/61) achieved a partial response, 49.0% (24\/49) became red blood cell transfusion-independent, and 56.8% (21\/37) became platelet transfusion-independent. Univariate logistic regression analysis identified duration from diagnosis (<jats:italic>P<\/jats:italic>\u2009=\u20090.040), baseline reticulocyte count (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), and platelet count (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) as predictors of response to romiplostim at 27\u00a0weeks. Receiver operating characteristic curve analysis identified a cutoff value of 30.77\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L at baseline as the threshold reticulocyte count to predict response to romiplostim in patients with refractory AA (sensitivity: 82.9%, specificity: 73.1%). Of note, the initial dose included in this analysis was lower than that used in real-world clinical practice, as data from the phase 2 dose-finding study were used. This study identified factors predicting response to romiplostim at 27\u00a0weeks.<\/jats:p>\n          <jats:p>Trial registration: ClinicalTrials.gov NCT02094417 and NCT02773290.<\/jats:p>","DOI":"10.1007\/s00277-025-06337-7","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T15:14:47Z","timestamp":1751382887000},"page":"4003-4011","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Predictive factors of romiplostim response in patients with refractory aplastic anemia: data from two clinical trials"],"prefix":"10.1007","volume":"104","author":[{"given":"Jun Ho","family":"Jang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinuko","family":"Mitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Tomiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Nagafuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Usuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Uoshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Fujisaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kosugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Kizaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Sawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michihiro","family":"Hidaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ichikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Yonemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Murotani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiya","family":"Ozawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Nakao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Wook","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"6337_CR1","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1056\/nejmra1413485","volume":"379","author":"NS Young","year":"2018","unstructured":"Young NS (2018) Aplastic anemia. N Engl J Med 379:1643\u20131656. https:\/\/doi.org\/10.1056\/nejmra1413485","journal-title":"N Engl J Med"},{"key":"6337_CR2","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1007\/s12185-015-1787-z","volume":"101","author":"M Miano","year":"2015","unstructured":"Miano M, Dufour C (2015) The diagnosis and treatment of aplastic anemia: a review. Int J Hematol 101:527\u2013535. https:\/\/doi.org\/10.1007\/s12185-015-1787-z","journal-title":"Int J Hematol"},{"key":"6337_CR3","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1111\/ejh.13182","volume":"102","author":"PC Boddu","year":"2019","unstructured":"Boddu PC, Kadia TM (2019) Molecular pathogenesis of acquired aplastic anemia. Eur J Haematol 102:103\u2013110. https:\/\/doi.org\/10.1111\/ejh.13182","journal-title":"Eur J Haematol"},{"key":"6337_CR4","unstructured":"Yamazaki H, Itagaki M, Usuki K, et al. Reference guide for aplastic anemia treatment, revised edition 2022. Grant-in-Aid for Scientific Research on Health, Labour and Welfare, Intractable Disease Policy Research Project, Research Group on Idiopathic Hematopoietic Disorders. MHLW Science Research Results Database. Accessed 20 October 2024."},{"key":"6337_CR5","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1111\/bjh.19236","volume":"204","author":"A Kulasekararaj","year":"2024","unstructured":"Kulasekararaj A, Cavenagh J, Dokal I, Foukaneli T, Gandhi S, Garg M, Griffin M, Hillmen P, Ireland R, Killick S, Mansour S, Mufti G, Potter V, Snowden J, Stanworth S, Zuha R, Marsh J, Committee BSH (2024) Guidelines for the diagnosis and management of adult aplastic anaemia: a British Society for Haematology Guideline. Br J Haematol 204:784\u2013804. https:\/\/doi.org\/10.1111\/bjh.19236","journal-title":"Br J Haematol"},{"key":"6337_CR6","doi-asserted-by":"publisher","first-page":"e562","DOI":"10.1016\/s2352-3026(19)30153-x","volume":"6","author":"JW Lee","year":"2019","unstructured":"Lee JW, Lee SE, Jung CW, Park S, Keta H, Park SK, Kim JA, Oh IH, Jang JH (2019) Romiplostim in patients with refractory aplastic anaemia previously treated with immunosuppressive therapy: a dose-finding and long-term treatment phase 2 trial. Lancet Haematol 6:e562\u2013572. https:\/\/doi.org\/10.1016\/s2352-3026(19)30153-x","journal-title":"Lancet Haematol"},{"key":"6337_CR7","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/bjh.17190","volume":"192","author":"JH Jang","year":"2021","unstructured":"Jang JH, Tomiyama Y, Miyazaki K et al (2021) Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase II\/III, multicentre, open-label study. Br J Haematol 192:190\u2013199. https:\/\/doi.org\/10.1111\/bjh.17190","journal-title":"Br J Haematol"},{"key":"6337_CR8","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/nejmoa1200931","volume":"367","author":"MJ Olnes","year":"2012","unstructured":"Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, Parikh AR, Soto S, Biancotto A, Feng X, Lozier J, Wu CO, Young NS, Dunbar CE (2012) Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 367:11\u201319. https:\/\/doi.org\/10.1056\/nejmoa1200931","journal-title":"N Engl J Med"},{"key":"6337_CR9","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1182\/blood.2019000478","volume":"133","author":"T Winkler","year":"2019","unstructured":"Winkler T, Fan X, Cooper J, Desmond R, Young DJ, Townsley DM, Scheinberg P, Grasmeder S, Larochelle A, Desierto M, Valdez J, Lotter J, Wu C, Shalhoub RN, Calvo KR, Young NS, Dunbar CE (2019) Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag. Blood 133:2575\u20132585. https:\/\/doi.org\/10.1182\/blood.2019000478","journal-title":"Blood"},{"key":"6337_CR10","doi-asserted-by":"publisher","first-page":"126","DOI":"10.3324\/haematol.2021.278413","volume":"107","author":"Y Zaimoku","year":"2022","unstructured":"Zaimoku Y, Patel BA, Shalhoub R, Groarke EM, Feng X, Wu CO, Young NS (2022) Predicting response of severe aplastic anemia to immunosuppression combined with eltrombopag. Haematologica 107:126\u2013133. https:\/\/doi.org\/10.3324\/haematol.2021.278413","journal-title":"Haematologica"},{"issue":"2","key":"6337_CR11","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/bjh.13853","volume":"172","author":"SB Killick","year":"2016","unstructured":"Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA (2016) Guidelines for the diagnosis and management of adult aplastic anaemia. British J Haematol 172(2):187\u2013207. https:\/\/doi.org\/10.1111\/bjh.13853","journal-title":"British J Haematol"},{"key":"6337_CR12","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/s41375-020-0950-6","volume":"35","author":"K Hosokawa","year":"2021","unstructured":"Hosokawa K, Yamazaki H, Tanabe M, Imi T, Sugimori N, Nakao S (2021) High-dose romiplostim accelerates hematologic recovery in patients with aplastic anemia refractory to eltrombopag. Leukemia 35:906\u2013909. https:\/\/doi.org\/10.1038\/s41375-020-0950-6","journal-title":"Leukemia"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-025-06337-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-025-06337-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-025-06337-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T07:48:39Z","timestamp":1757663319000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-025-06337-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":12,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["6337"],"URL":"https:\/\/doi.org\/10.1007\/s00277-025-06337-7","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]},"assertion":[{"value":"12 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In the phase 2 dose-finding study, the ethical considerations were as follows: approval by the Ethics Review Board, adherence to the Declaration of Helsinki, provision of informed consent by all patients at enrollment, and clinical trial registration at ClinicalTrials.gov (NCT02094417). In the phase 2\/3 study, the ethical considerations were as follows: approval by the Institutional Review Board at each center, adherence to the Declaration of Helsinki and International Conference on Harmonisation of Good Clinical Practice guidelines, provision of informed consent by all participants, and clinical trial registration at ClinicalTrials.gov (NCT02773290). Consent for secondary use of the data in this study was also obtained.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"K. Mitani received speakers bureau fees from Celgene K.K.; Otsuka Pharmaceutical Co., Ltd.; Bristol-Myers Squibb K.K.; Novartis Pharma K.K.; and Kyowa Kirin Co., Ltd.; and received research funding from Chugai Pharmaceutical Co., Ltd.; Kyowa Kirin Co., Ltd.; and Takeda Pharmaceutical Co., Ltd. Y.T. received speakers bureau fees from Kyowa Kirin Co., Ltd.; Novartis Pharma K.K.; Kissei Pharmaceutical Co., Ltd.; Sysmex Corporation; Chugai Pharmaceutical Co., Ltd.; and UCB Japan Co., Ltd.; received consultancy fees from Swedish Orphan Biovitrum Japan Co., Ltd.; Medical & Biological Laboratories Co., Ltd.; Kissei Pharmaceutical Co., Ltd.; Novartis Pharma K.K.; and Sysmex Corporation; and had membership on Board of Directors or advisory committees for Novartis Pharma K.K.; Sysmex Corporation; Takeda Pharmaceutical Co., Ltd.; and Argenx Japan K.K. K. Miyazaki received speakers bureau fees from Kyowa Kirin Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Pfizer Japan Inc.; Takeda Pharmaceutical Co., Ltd.; MSD K.K.; Novartis Pharma K.K.; Novo Nordisk Pharma Ltd.; KM Biologics Co., Ltd.; Nihon Pharmaceutical Co., Ltd.; and CSL Behring K.K.; and received research funding from Kyowa Kirin Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Pfizer Japan Inc.; Daiichi Sankyo Co., Ltd.; Astellas Pharma Inc.; and Otsuka Pharmaceutical Co., Ltd. K.N. received speakers bureau fees from Kyowa Kirin Co., Ltd. K.U. received speakers bureau fees from Novartis Pharma K.K.; AbbVie G.K.; Alexion Pharmaceuticals, Inc.; Amgen K.K.; Asahi Kasei Pharma Corporation; AstraZeneca K.K.; Bristol-Myers Squibb K.K.; Chugai Pharmaceutical Co., Ltd.; Eisai Co., Ltd.; Incyte Biosciences Japan G.K.; Kyowa Kirin Co., Ltd.; Meiji Seika Pharma Co., Ltd.; Nippon Shinyaku Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Otsuka Pharmaceutical Co., Ltd.; PharmaEssentia Japan K.K.; Sanofi K.K.; Takeda Pharmaceutical Co., Ltd.; and Janssen Pharmaceutical K.K.; received research funding from Astellas Pharma Inc.; AbbVie G.K.; Alexion Pharmaceuticals, Inc.; Apellis Pharmaceuticals, Inc.; Bristol-Myers Squibb K.K.; Celgene K.K.; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; Eisai Co., Ltd.; Incyte Biosciences Japan G.K.; Kyowa Kirin Co., Ltd.; MSD K.K.; Nippon Shinyaku Co., Ltd.; Novartis Pharma K.K.; Ohara Pharmaceutical Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Otsuka Pharmaceutical Co., Ltd.; Pfizer Japan Inc.; Sanofi K.K.; Takeda Pharmaceutical Co., Ltd.; and Yakult Honsha Co., Ltd.; and received consultancy fees from Alnylam Japan K.K.; Chugai Pharmaceutical Co., Ltd.; Ohara Pharmaceutical Co., Ltd.; and Swedish Orphan Biovitrum Japan Co., Ltd. N.U. received honoraria from Bristol-Myers Squibb K.K.; Janssen Pharmaceutical K.K.; Chugai Pharmaceutical Co., Ltd.; Nippon Shinyaku Co., Ltd.; and Otsuka Pharmaceutical Co., Ltd. T.F. received speakers bureau fees from Kyowa Kirin Co., Ltd.; Novartis Pharma K.K.; AbbVie G.K.; Janssen Pharmaceutical K.K.; Bristol-Myers Squibb K.K.; and Chugai Pharmaceutical Co., Ltd. H.K. received honoraria from Bristol-Myers Squibb K.K.; Celgene K.K.; Chugai Pharmaceutical Co., Ltd.; Janssen Pharmaceutical K.K.; Japan Blood Products Organization; Kyowa Kirin Co., Ltd.; MSD K.K.; Novartis Pharma K.K.; Ono Pharmaceutical Co., Ltd.; Sanofi K.K.; Takeda Pharmaceutical Co., Ltd.; Nippon Shinyaku Co. Ltd.; Novo Nordisk Pharma Ltd.; Kissei Pharmaceutical Co. Ltd.; GlaxoSmithKline K.K.; Daiichi Sankyo Co., Ltd.; and AstraZeneca K.K. I.M. received speakers bureau fees from Sanofi K.K.; Bristol-Myers Squibb K.K.; SymBio Pharmaceuticals Ltd.; AstraZeneca K.K.; Chugai Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Ono Pharmaceutical Co., Ltd.; AbbVie G.K.; Otsuka Pharmaceutical Co., Ltd.; Astellas Pharma Inc.; Pfizer Japan Inc.; Novartis Pharma K.K.; and Janssen Pharmaceutical K.K.; received research funding from Chugai Pharmaceutical Co., Ltd.; Kyowa Kirin Co., Ltd.; Sumitomo Pharma Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma Corporation; Nippon Shinyaku Co., Ltd.; Eisai Co., Ltd.; Asahi Kasei Pharma Corporation; AbbVie G.K.; Taiho Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; Nippon Kayaku Co., Ltd.; CSL Behring K.K.; Ayumi Pharmaceutical Corporation; and Eli Lily Japan K.K.; and received consultancy fees from Otsuka Pharmaceutical Co., Ltd. M.K. received speakers bureau fees from Bristol-Myers Squibb K.K.; Novartis Pharma K.K.; Janssen Pharmaceutical K.K.; Nippon Shinyaku Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; and Ono Pharmaceutical Co., Ltd. M. Sawa received honoraria from GlaxoSmithKline K.K.; Daiichi Sankyo Co., Ltd.; AstraZeneca K.K.; Janssen Pharmaceutical K.K.; SymBio Pharmaceuticals Ltd.; CSL Behring K.K.; AbbVie G.K.; Mundipharma K.K.; Shire Japan K.K.; Mochida Pharmaceutical Co., Ltd.; Celgene K.K.; Sanofi K.K.; Takeda Pharmaceutical Co., Ltd.; Sumitomo Pharma Co., Ltd.; Otsuka Pharmaceutical Co., Ltd.; Eisai Co., Ltd.; Novartis Pharma K.K.; Asahi Kasei Pharma Corporation; Bristol-Myers Squibb K.K.; MSD K.K.; Ono Pharmaceutical Co., Ltd.; Nippon Shinyaku Co., Ltd.; Astellas Pharma Inc.; Pfizer Japan Inc.; Chugai Pharmaceutical Co., Ltd.; and Kyowa Kirin Co., Ltd. M.H. received honoraria from Chugai Pharmaceutical Co., Ltd. and JCR Pharmaceuticals Co., Ltd. S.I. received honoraria from Meiji Seika Pharma Co., Ltd.; and received research funding from AstraZeneca K.K. and Beigene Japan G.K. Y.Y. received honoraria from Alexion Pharmaceuticals Inc. and Novartis Pharma K.K.; and received research funding from Chugai Pharmaceutical Co., Ltd. K. Murotani received honoraria from Kyowa Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Taiho Pharmaceutical Co., Ltd., MSD K.K., Nihon Shinyaku Co., Ltd. and Pfizer Japan Inc. M. Shimizu is currently employed at Kyowa Kirin Co., Ltd. A.M. received honoraria from Chugai Pharmaceutical Co., Ltd.; Alexion Pharmaceuticals Inc.; Nippon Shinyaku Co., Ltd.; Sumitomo Pharma Co., Ltd.; and Novartis Pharma K.K.; and received consultancy fees from Kyowa Kirin Co., Ltd. K.O. received honoraria from Human Life CORD Japan Inc.; Otsuka Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma Corporation; AbbVie G.K.; and Novartis Pharma K.K.; received research funding from Japan Agency for Medical Research and Development; received consultancy fees from Takara Bio Inc. and Human Life CORD Japan Inc.; is a current equity holder in Terumo Corporation; and has a membership on their Board of Directors or advisory committees. S.N. received honoraria from Novartis Pharma K.K. and Kyowa Kirin Co., Ltd.; SymBio Pharmaceuticals Ltd.; Sanofi K.K.; Asahi Kasei Pharma Corporation; Pfizer Japan Inc.; Swedish Orphan Biovitrum Japan Co., Ltd.; Alexion Pharmaceuticals, Inc.; received consultancy fees from SymBio Pharmaceuticals Ltd.; and received research funding from Alexion Pharmaceuticals Inc. J.W.L. received speakers bureau fees and grants from Alexion and AstraZeneca Rare Disease; and received consultancy fees from Kyowa Kirin Co., Ltd., Novartis Pharma K.K., and Sanofi K.K. The remaining authors declare no competing financial interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}