{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:51:30Z","timestamp":1789480290301,"version":"build-2803163510"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100015990","name":"Sanofi K.K.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015990","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sutimlimab, a complement inhibitor, has recently been approved in Japan for treating cold agglutinin disease (CAD). We report the safety and efficacy of sutimlimab in Japanese patients with CAD who completed a global phase 3 clinical trial (CARDINAL\/CADENZA: 26-week treatment with 1\u20132\u00a0years of open-label extension [OLE] periods) and subsequently participated in the Japanese OLE study. Patients with a recent history of blood transfusion (CARDINAL, n\u2009=\u20093) and those without (CADENZA, n\u2009=\u20094) were analyzed (71.4% female; median [range] baseline age: 70 [46\u201383] years). For CARDINAL\/CADENZA, the treatment duration (median [range]) was 140.9 (104.9\u2013157.3) weeks, and the cessation period was 70 (61\u2013133) weeks. For the Japanese OLE study, the treatment duration was 47.1 (15.1\u201349.1) weeks. Three (42.9%) patients experienced treatment-related and treatment-emergent adverse events (TEAEs): injection site erythema, cystitis bacterial, viral infection, and blood pressure increased during CARDINAL\/CADENZA. One (14.3%) patient experienced one treatment-related TEAE (urinary tract infection) during the Japanese OLE study. One patient died of renal failure, considered unrelated to sutimlimab, that was exacerbated by hepatorenal syndrome due to liver cirrhosis and bacterial peritonitis, in addition to CKD. Hemoglobin and bilirubin levels improved during treatment but deteriorated after withdrawal and recovered on retreatment. Sutimlimab was well tolerated over a median of 3.8\u00a0years, with no new safety concerns identified during retreatment.<\/jats:p>","DOI":"10.1007\/s12185-024-03842-9","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T17:02:19Z","timestamp":1728925339000},"page":"656-664","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Long-term safety profile of sutimlimab in adult Japanese patients with cold agglutinin disease"],"prefix":"10.1007","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4429-7227","authenticated-orcid":false,"given":"Yoshitaka","family":"Miyakawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichi","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Nishimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Tahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"3842_CR1","doi-asserted-by":"publisher","DOI":"10.1097\/hs9.0000000000000879","volume":"7","author":"S Berentsen","year":"2023","unstructured":"Berentsen S. Sutimlimab for the treatment of cold agglutinin disease. Hemasphere. 2023;7:e879. https:\/\/doi.org\/10.1097\/hs9.0000000000000879.","journal-title":"Hemasphere"},{"key":"3842_CR2","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.2217\/imt-2022-0085","volume":"14","author":"S Berentsen","year":"2022","unstructured":"Berentsen S, Barcellini W, D\u2019Sa S, Jilma B. Sutimlimab for treatment of cold agglutinin disease: why, how and for whom? Immunotherapy. 2022;14:1191\u2013204. https:\/\/doi.org\/10.2217\/imt-2022-0085.","journal-title":"Immunotherapy"},{"key":"3842_CR3","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1182\/blood.2019003809","volume":"137","author":"S Berentsen","year":"2021","unstructured":"Berentsen S. How I treat cold agglutinin disease. Blood. 2021;137:1295\u2013303. https:\/\/doi.org\/10.1182\/blood.2019003809.","journal-title":"Blood"},{"key":"3842_CR4","first-page":"460","volume":"91","author":"S Berentsen","year":"2006","unstructured":"Berentsen S, Ulvestad E, Langholm R, et al. Primary chronic cold agglutinin disease: a population based clinical study of 86 patients. Haematologica. 2006;91:460\u20136.","journal-title":"Haematologica"},{"key":"3842_CR5","doi-asserted-by":"publisher","first-page":"95","DOI":"10.2991\/chi.k.200706.001","volume":"2","author":"AP Gabbard","year":"2020","unstructured":"Gabbard AP, Booth GS. Cold agglutinin disease. Clin Hematol Int. 2020;2:95\u2013100. https:\/\/doi.org\/10.2991\/chi.k.200706.001.","journal-title":"Clin Hematol Int"},{"key":"3842_CR6","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1053\/j.seminhematol.2018.04.002","volume":"55","author":"S Berentsen","year":"2018","unstructured":"Berentsen S. Complement activation and inhibition in autoimmune hemolytic anemia: focus on cold agglutinin disease. Semin Hematol. 2018;55:141\u20139. https:\/\/doi.org\/10.1053\/j.seminhematol.2018.04.002.","journal-title":"Semin Hematol"},{"key":"3842_CR7","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.blre.2012.01.002","volume":"26","author":"S Berentsen","year":"2012","unstructured":"Berentsen S, Tj\u00f8nnfjord GE. Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia. Blood Rev. 2012;26:107\u201315. https:\/\/doi.org\/10.1016\/j.blre.2012.01.002.","journal-title":"Blood Rev"},{"key":"3842_CR8","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1182\/blood.2020005674","volume":"136","author":"S Berentsen","year":"2020","unstructured":"Berentsen S, Barcellini W, D\u2019Sa S, et al. Cold agglutinin disease revisited: a multinational, observational study of 232 patients. Blood. 2020;136:480\u20138. https:\/\/doi.org\/10.1182\/blood.2020005674.","journal-title":"Blood"},{"key":"3842_CR9","doi-asserted-by":"publisher","first-page":"E262","DOI":"10.1002\/ajh.26196","volume":"96","author":"DL Hansen","year":"2021","unstructured":"Hansen DL, Berentsen S, Fattizzo B, Hansen PL, Barcellini W, Frederiksen H. Seasonal variation in the incidence of cold agglutinin disease in Norway, Denmark, and Italy. Am J Hematol. 2021;96:E262\u20135. https:\/\/doi.org\/10.1002\/ajh.26196.","journal-title":"Am J Hematol"},{"key":"3842_CR10","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/trf.16765","volume":"62","author":"CJ Patriquin","year":"2022","unstructured":"Patriquin CJ, Pavenski K. O, wind, if winter comes \u2026 will symptoms be far behind?: Exploring the seasonality (or lack thereof) and management of cold agglutinin disease. Transfusion. 2022;62:2\u201310. https:\/\/doi.org\/10.1111\/trf.16765.","journal-title":"Transfusion"},{"key":"3842_CR11","doi-asserted-by":"publisher","unstructured":"Lyckholm LJ, Edmond MB. Images in clinical medicine. Seasonal hemolysis due to cold-agglutinin syndrome. N Engl J Med 1996;334:437. https:\/\/doi.org\/10.1056\/nejm199602153340705.","DOI":"10.1056\/nejm199602153340705"},{"key":"3842_CR12","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/trf.16745","volume":"62","author":"A R\u00f6th","year":"2022","unstructured":"R\u00f6th A, Fryzek J, Jiang X, et al. Complement-mediated hemolysis persists year round in patients with cold agglutinin disease. Transfusion. 2022;62:51\u20139. https:\/\/doi.org\/10.1111\/trf.16745.","journal-title":"Transfusion"},{"key":"3842_CR13","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1111\/ejh.13903","volume":"110","author":"A R\u00f6th","year":"2023","unstructured":"R\u00f6th A, Broome CM, Barcellini W, et al. Sutimlimab provides clinically meaningful improvements in patient-reported outcomes in patients with cold agglutinin disease: Results from the randomised, placebo-controlled, Phase 3 CADENZA study. Eur J Haematol. 2023;110:280\u20138. https:\/\/doi.org\/10.1111\/ejh.13903.","journal-title":"Eur J Haematol"},{"key":"3842_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2019.100648","volume":"41","author":"U J\u00e4ger","year":"2020","unstructured":"J\u00e4ger U, Barcellini W, Broome CM, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: recommendations from the First International Consensus Meeting. Blood Rev. 2020;41:100648. https:\/\/doi.org\/10.1016\/j.blre.2019.100648.","journal-title":"Blood Rev"},{"key":"3842_CR15","doi-asserted-by":"publisher","first-page":"4015","DOI":"10.1182\/blood-2014-02-556027","volume":"123","author":"J Shi","year":"2014","unstructured":"Shi J, Rose EL, Singh A, et al. TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins. Blood. 2014;123:4015\u201322. https:\/\/doi.org\/10.1182\/blood-2014-02-556027.","journal-title":"Blood"},{"key":"3842_CR16","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1002\/cpt.1111","volume":"104","author":"J Bartko","year":"2018","unstructured":"Bartko J, Schoergenhofer C, Schwameis M, et al. A randomized, first-in-human, healthy volunteer trial of sutimlimab, a humanized antibody for the specific inhibition of the classical complement pathway. Clin Pharmacol Ther. 2018;104:655\u201363. https:\/\/doi.org\/10.1002\/cpt.1111.","journal-title":"Clin Pharmacol Ther"},{"key":"3842_CR17","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1056\/NEJMoa2027760","volume":"384","author":"A R\u00f6th","year":"2021","unstructured":"R\u00f6th A, Barcellini W, D\u2019Sa S, et al. Sutimlimab in cold agglutinin disease. N Engl J Med. 2021;384:1323\u201334. https:\/\/doi.org\/10.1056\/NEJMoa2027760.","journal-title":"N Engl J Med"},{"key":"3842_CR18","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1182\/blood.2021014955","volume":"140","author":"A R\u00f6th","year":"2022","unstructured":"R\u00f6th A, Berentsen S, Barcellini W, et al. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial. Blood. 2022;140:980\u201391. https:\/\/doi.org\/10.1182\/blood.2021014955.","journal-title":"Blood"},{"key":"3842_CR19","unstructured":"U.S. Food & Drug Administration. FDA approves treatment for adults with rare type of anemia 2022 [updated 02\/04\/2022]. Available from: https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-treatment-adults-rare-type-anemia."},{"key":"3842_CR20","unstructured":"Pharmaceuticals and Medical Devices Agency. Prescribing information: ENJAYMO for I.V. infusion 2022 [updated June 2023]. Available from: https:\/\/www.info.pmda.go.jp\/go\/pack\/6399431A1023_1_02\/."},{"key":"3842_CR21","unstructured":"European Medicines Agency. Enjaymo: EAPR - Product Information 2022 [updated 13 April 2023]. Available from: https:\/\/www.ema.europa.eu\/documents\/product-information\/enjaymo-epar-product-information_en.pdf."},{"key":"3842_CR22","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1002\/ajh.26965","volume":"98","author":"A R\u00f6th","year":"2023","unstructured":"R\u00f6th A, Barcellini W, D\u2019Sa S, et al. Sustained inhibition of complement C1s with sutimlimab over 2 years in patients with cold agglutinin disease. Am J Hematol. 2023;98:1246\u201353. https:\/\/doi.org\/10.1002\/ajh.26965.","journal-title":"Am J Hematol"},{"key":"3842_CR23","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1177\/0961203309346508","volume":"19","author":"R Aggarwal","year":"2010","unstructured":"Aggarwal R, Sestak AL, D'Souza A, Dillon SP, Namjou B, Scofield RH.\u00a0Complete complement deficiency in a large cohort of familial systemic lupus erythematosus. Lupus. 2010;19:52\u20137. https:\/\/doi.org\/10.1177\/0961203309346508.","journal-title":"Lupus"},{"key":"3842_CR24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.791429","volume":"12","author":"B Fattizzo","year":"2021","unstructured":"Fattizzo B, Pasquale R, Bellani V, Barcellini W, Kulasekararaj AG. Complement mediated hemolytic anemias in the COVID-19 era: Case series and review of the literature. Front Immunol. 2021;12: 791429. https:\/\/doi.org\/10.3389\/fimmu.2021.791429.","journal-title":"Front Immunol"},{"key":"3842_CR25","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1002\/ajh.27234","volume":"99","author":"B Fattizzo","year":"2024","unstructured":"Fattizzo B, R\u00f6th A, Broome CM, et al. COVID-19 vaccine safety and immunogenicity in patients with cold agglutinin disease receiving concomitant sutimlimab. Am J Hematol. 2024;99:789\u201391. https:\/\/doi.org\/10.1002\/ajh.27234.","journal-title":"Am J Hematol"},{"key":"3842_CR26","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1182\/bloodadvances.2019001321","volume":"4","author":"G Gelbenegger","year":"2020","unstructured":"Gelbenegger G, Schoergenhofer C, Derhaschnig U, et al. Inhibition of complement C1s in patients with cold agglutinin disease: lessons learned from a named patient program. Blood Adv. 2020;4:997\u20131005. https:\/\/doi.org\/10.1182\/bloodadvances.2019001321.","journal-title":"Blood Adv"},{"key":"3842_CR27","doi-asserted-by":"publisher","first-page":"e59","DOI":"10.1111\/bjh.18289","volume":"198","author":"G Gelbenegger","year":"2022","unstructured":"Gelbenegger G, Jaeger U, Fillitz M, et al. Sustained sutimlimab response for 3 years in patients with cold agglutinin disease: A phase I, open-label, extension trial. Br J Haematol. 2022;198:e59\u201362. https:\/\/doi.org\/10.1111\/bjh.18289.","journal-title":"Br J Haematol"},{"key":"3842_CR28","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/s0025-7125(16)30345-5","volume":"76","author":"IA Tabbara","year":"1992","unstructured":"Tabbara IA. Hemolytic anemias. Diagnosis and management. Med Clin North Am. 1992;76:649\u201368. https:\/\/doi.org\/10.1016\/s0025-7125(16)30345-5.","journal-title":"Med Clin North Am"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-024-03842-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-024-03842-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-024-03842-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T14:05:47Z","timestamp":1732543547000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-024-03842-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,14]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["3842"],"URL":"https:\/\/doi.org\/10.1007\/s12185-024-03842-9","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,14]]},"assertion":[{"value":"24 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"YM received research grants from Sanofi K.K., Pfizer Japan Inc., Novartis Pharma K.K., Kissei Pharmaceutical Co., Ltd., Argenx Japan K.K., Novo Nordisk Pharma Ltd., CSL Behring K.K., BioMarin Pharmaceutical Japan K.K., Chugai Pharmaceutical Co., Ltd., and Janssen Pharmaceutical K.K. and received lecture fees from Sanofi K.K., Asahi Kasei Medical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Alexion Pharmaceuticals, Inc., Kissei Pharmaceutical Co. Ltd., and Kyowa Kirin Co., Ltd. and participated in advisory boards held by Sanofi K.K. and Pfizer Japan Inc and\u00a0was involved in consultancy for Argenx Japan K.K., Zenyaku Holdings Co., Ltd., and Kissei Pharmaceutical Co., Ltd. YO received research grants from Mochida Pharmaceutical Co., Ltd., Fortrea Japan Inc., Janssen Pharmaceutical K.K., FUJIFILM K.K., AbbVie GK., and Otsuka Pharmaceutical Co., Ltd. and received honoraria\/payment from Novartis Pharma K.K, Chugai Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., AstraZeneca K.K., Daiichi Sankyo Co., Ltd., and AbbVie GK. JN received honoraria or lecture fee from Swedish Orphan Biovitrum Japan K.K, Alexion Pharmaceuticals, Inc., Roche Diagnostics K.K., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., BioCryst Pharmaceuticals, Inc., and Sanofi K.K. MN and OK are employees at Sanofi K.K. and ST was employee at Sanofi K.K at the time when the Japan OLE study was conducted and the data were analyzed. ES and MY have no conflict of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}