{"title":"日本成年冷凝集素病患者使用 sutimlimab 的长期安全性概况。","authors":"Yoshitaka Miyakawa, Eriko Sato, Yoshiaki Ogawa, Jun-Ichi Nishimura, Masashi Nishimi, Osamu Kawaguchi, Sayaka Tahara, Masaki Yamaguchi","doi":"10.1007/s12185-024-03842-9","DOIUrl":null,"url":null,"abstract":"<p><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 1-2 years of open-label extension [OLE] periods) and subsequently participated in the Japanese OLE study. Patients with a recent history of blood transfusion (CARDINAL, n = 3) and those without (CADENZA, n = 4) were analyzed (71.4% female; median [range] baseline age: 70 [46-83] years). For CARDINAL/CADENZA, the treatment duration (median [range]) was 140.9 (104.9-157.3) weeks, and the cessation period was 70 (61-133) weeks. For the Japanese OLE study, the treatment duration was 47.1 (15.1-49.1) 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 years, with no new safety concerns identified during retreatment.</p>","PeriodicalId":13992,"journal":{"name":"International Journal of Hematology","volume":" ","pages":"656-664"},"PeriodicalIF":1.7000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11588873/pdf/","citationCount":"0","resultStr":"{\"title\":\"Long-term safety profile of sutimlimab in adult Japanese patients with cold agglutinin disease.\",\"authors\":\"Yoshitaka Miyakawa, Eriko Sato, Yoshiaki Ogawa, Jun-Ichi Nishimura, Masashi Nishimi, Osamu Kawaguchi, Sayaka Tahara, Masaki Yamaguchi\",\"doi\":\"10.1007/s12185-024-03842-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><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 1-2 years of open-label extension [OLE] periods) and subsequently participated in the Japanese OLE study. Patients with a recent history of blood transfusion (CARDINAL, n = 3) and those without (CADENZA, n = 4) were analyzed (71.4% female; median [range] baseline age: 70 [46-83] years). For CARDINAL/CADENZA, the treatment duration (median [range]) was 140.9 (104.9-157.3) weeks, and the cessation period was 70 (61-133) weeks. For the Japanese OLE study, the treatment duration was 47.1 (15.1-49.1) 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 years, with no new safety concerns identified during retreatment.</p>\",\"PeriodicalId\":13992,\"journal\":{\"name\":\"International Journal of Hematology\",\"volume\":\" \",\"pages\":\"656-664\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11588873/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Hematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12185-024-03842-9\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12185-024-03842-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/14 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
补体抑制剂 Sutimlimab 最近在日本获批用于治疗冷凝集素病(CAD)。我们报告了苏替米单抗在日本 CAD 患者中的安全性和疗效,这些患者完成了全球 3 期临床试验(CARDINAL/CADENZA:26 周治疗,1-2 年开放标签延长期 [OLE]),随后参加了日本 OLE 研究。研究分析了近期有输血史的患者(CARDINAL,n = 3)和无输血史的患者(CADENZA,n = 4)(71.4% 为女性;中位数[范围]基线年龄:70 [46-83] 岁)。CARDINAL/CADENZA的治疗时间(中位数[范围])为140.9(104.9-157.3)周,停药时间为70(61-133)周。在日本的 OLE 研究中,治疗持续时间为 47.1(15.1-49.1)周。三名(42.9%)患者在使用 CARDINAL/CADENZA 期间出现了治疗相关和治疗突发不良事件(TEAEs):注射部位红斑、细菌性膀胱炎、病毒感染和血压升高。在日本的 OLE 研究中,有一名(14.3%)患者出现了治疗相关的 TEAE(尿路感染)。一名患者死于肾功能衰竭,据认为与 sutimlimab 无关,除了慢性肾功能衰竭外,肝硬化和细菌性腹膜炎导致的肝肾综合征也加剧了肾功能衰竭。治疗期间血红蛋白和胆红素水平有所改善,但停药后病情恶化,再次治疗后病情恢复。Sutimlimab在3.8年的中位治疗期间耐受性良好,再治疗期间未发现新的安全性问题。
Long-term safety profile of sutimlimab in adult Japanese patients with cold agglutinin disease.
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 1-2 years of open-label extension [OLE] periods) and subsequently participated in the Japanese OLE study. Patients with a recent history of blood transfusion (CARDINAL, n = 3) and those without (CADENZA, n = 4) were analyzed (71.4% female; median [range] baseline age: 70 [46-83] years). For CARDINAL/CADENZA, the treatment duration (median [range]) was 140.9 (104.9-157.3) weeks, and the cessation period was 70 (61-133) weeks. For the Japanese OLE study, the treatment duration was 47.1 (15.1-49.1) 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 years, with no new safety concerns identified during retreatment.
期刊介绍:
The International Journal of Hematology, the official journal of the Japanese Society of Hematology, has a long history of publishing leading research in hematology. The journal comprises articles that contribute to progress in research not only in basic hematology but also in clinical hematology, aiming to cover all aspects of this field, namely, erythrocytes, leukocytes and hematopoiesis, hemostasis, thrombosis and vascular biology, hematological malignancies, transplantation, and cell therapy. The expanded [Progress in Hematology] section integrates such relevant fields as the cell biology of stem cells and cancer cells, and clinical research in inflammation, cancer, and thrombosis. Reports on results of clinical trials are also included, thus contributing to the aim of fostering communication among researchers in the growing field of modern hematology. The journal provides the best of up-to-date information on modern hematology, presenting readers with high-impact, original work focusing on pivotal issues.