{"title":"Vadadustat在慢性肾病相关性贫血患者中的安全性和有效性：日本上市后监测的中期分析","authors":"Masaomi Nangaku, Kazuyo Sasaki, Jing Bi, Kiichiro Ueta, Kenichi Nishimura, Takafumi Hashimoto, Mihoko Hata","doi":"10.1007/s12325-025-03272-x","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat chronic kidney disease (CKD)-related anemia. This interim analysis presents findings from postmarketing surveillance (PMS) conducted in Japan, assessing the safety and effectiveness of vadadustat in real-world clinical practice.</p><h3>Methods</h3><p>This ongoing 2-year observational, multicenter, prospective surveillance collected data from November 2020 to June 2024 to assess adverse drug reactions (ADRs) and hemoglobin (Hb) levels in patients with CKD-related anemia. ADRs of special interest included malignant tumors, thromboembolism, hepatic impairment, hypertension, cardiovascular events excluding thromboembolism, retinal hemorrhage-related ADRs, and the progression of autosomal dominant polycystic kidney disease.</p><h3>Results</h3><p>This interim analysis included 2263 patients enrolled from 420 sites across Japan, with 2191 and 2142 patients analyzed for safety and effectiveness, respectively. The safety analysis population comprised 1429 patients with non-dialysis-dependent (NDD)-CKD, 174 with peritoneal dialysis-dependent (PD)-CKD, and 588 with hemodialysis-dependent (HD)-CKD. The median treatment duration was 365.0 days overall (365.0 days for NDD-CKD and PD-CKD, and 189.0 days for HD-CKD). Treatment with vadadustat was discontinued in approximately half of the patients in each CKD group during the observation period. ADRs and serious ADRs were observed in 14.79% and 6.30% of the patients, respectively. The most common ADRs were nausea (1.19%) and diarrhea (1.14%). ADRs of special interest occurring in more than 1% of patients were malignant tumors (1.14%) and thromboembolism (1.05%).</p><p>The mean changes in Hb levels from baseline to 12 months in patients who switched from erythropoiesis-stimulating agents (ESAs) to vadadustat and in those without prior ESA use were as follows: 0.30 g/dL and 1.12 g/dL for patients with NDD-CKD; 0.30 g/dL and 0.34 g/dL for PD-CKD; and 0.18 g/dL and 0.90 g/dL for HD-CKD, respectively. Across all CKD subgroups, mean Hb levels increased after treatment with vadadustat in patients with baseline Hb levels < 10 g/dL.</p><h3>Conclusion</h3><p>In this interim analysis, we identified no new safety concerns beyond those outlined in the Japanese package insert for vadadustat, which is based on the results from pivotal clinical trials. The ongoing PMS will continue to offer valuable insights into the safety and effectiveness of vadadustat in real-world clinical practice.</p><h3>Trial Registration</h3><p>UMIN000042349.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4486 - 4509"},"PeriodicalIF":4.0000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03272-x.pdf","citationCount":"0","resultStr":"{\"title\":\"Real-World Safety and Effectiveness of Vadadustat in Patients with Chronic Kidney Disease-Related Anemia: Interim Analysis of Postmarketing Surveillance in Japan\",\"authors\":\"Masaomi Nangaku, Kazuyo Sasaki, Jing Bi, Kiichiro Ueta, Kenichi Nishimura, Takafumi Hashimoto, Mihoko Hata\",\"doi\":\"10.1007/s12325-025-03272-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat chronic kidney disease (CKD)-related anemia. This interim analysis presents findings from postmarketing surveillance (PMS) conducted in Japan, assessing the safety and effectiveness of vadadustat in real-world clinical practice.</p><h3>Methods</h3><p>This ongoing 2-year observational, multicenter, prospective surveillance collected data from November 2020 to June 2024 to assess adverse drug reactions (ADRs) and hemoglobin (Hb) levels in patients with CKD-related anemia. ADRs of special interest included malignant tumors, thromboembolism, hepatic impairment, hypertension, cardiovascular events excluding thromboembolism, retinal hemorrhage-related ADRs, and the progression of autosomal dominant polycystic kidney disease.</p><h3>Results</h3><p>This interim analysis included 2263 patients enrolled from 420 sites across Japan, with 2191 and 2142 patients analyzed for safety and effectiveness, respectively. The safety analysis population comprised 1429 patients with non-dialysis-dependent (NDD)-CKD, 174 with peritoneal dialysis-dependent (PD)-CKD, and 588 with hemodialysis-dependent (HD)-CKD. The median treatment duration was 365.0 days overall (365.0 days for NDD-CKD and PD-CKD, and 189.0 days for HD-CKD). Treatment with vadadustat was discontinued in approximately half of the patients in each CKD group during the observation period. ADRs and serious ADRs were observed in 14.79% and 6.30% of the patients, respectively. The most common ADRs were nausea (1.19%) and diarrhea (1.14%). ADRs of special interest occurring in more than 1% of patients were malignant tumors (1.14%) and thromboembolism (1.05%).</p><p>The mean changes in Hb levels from baseline to 12 months in patients who switched from erythropoiesis-stimulating agents (ESAs) to vadadustat and in those without prior ESA use were as follows: 0.30 g/dL and 1.12 g/dL for patients with NDD-CKD; 0.30 g/dL and 0.34 g/dL for PD-CKD; and 0.18 g/dL and 0.90 g/dL for HD-CKD, respectively. Across all CKD subgroups, mean Hb levels increased after treatment with vadadustat in patients with baseline Hb levels < 10 g/dL.</p><h3>Conclusion</h3><p>In this interim analysis, we identified no new safety concerns beyond those outlined in the Japanese package insert for vadadustat, which is based on the results from pivotal clinical trials. The ongoing PMS will continue to offer valuable insights into the safety and effectiveness of vadadustat in real-world clinical practice.</p><h3>Trial Registration</h3><p>UMIN000042349.</p></div>\",\"PeriodicalId\":7482,\"journal\":{\"name\":\"Advances in Therapy\",\"volume\":\"42 9\",\"pages\":\"4486 - 4509\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s12325-025-03272-x.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12325-025-03272-x\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Therapy","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12325-025-03272-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Real-World Safety and Effectiveness of Vadadustat in Patients with Chronic Kidney Disease-Related Anemia: Interim Analysis of Postmarketing Surveillance in Japan
Introduction
Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat chronic kidney disease (CKD)-related anemia. This interim analysis presents findings from postmarketing surveillance (PMS) conducted in Japan, assessing the safety and effectiveness of vadadustat in real-world clinical practice.
Methods
This ongoing 2-year observational, multicenter, prospective surveillance collected data from November 2020 to June 2024 to assess adverse drug reactions (ADRs) and hemoglobin (Hb) levels in patients with CKD-related anemia. ADRs of special interest included malignant tumors, thromboembolism, hepatic impairment, hypertension, cardiovascular events excluding thromboembolism, retinal hemorrhage-related ADRs, and the progression of autosomal dominant polycystic kidney disease.
Results
This interim analysis included 2263 patients enrolled from 420 sites across Japan, with 2191 and 2142 patients analyzed for safety and effectiveness, respectively. The safety analysis population comprised 1429 patients with non-dialysis-dependent (NDD)-CKD, 174 with peritoneal dialysis-dependent (PD)-CKD, and 588 with hemodialysis-dependent (HD)-CKD. The median treatment duration was 365.0 days overall (365.0 days for NDD-CKD and PD-CKD, and 189.0 days for HD-CKD). Treatment with vadadustat was discontinued in approximately half of the patients in each CKD group during the observation period. ADRs and serious ADRs were observed in 14.79% and 6.30% of the patients, respectively. The most common ADRs were nausea (1.19%) and diarrhea (1.14%). ADRs of special interest occurring in more than 1% of patients were malignant tumors (1.14%) and thromboembolism (1.05%).
The mean changes in Hb levels from baseline to 12 months in patients who switched from erythropoiesis-stimulating agents (ESAs) to vadadustat and in those without prior ESA use were as follows: 0.30 g/dL and 1.12 g/dL for patients with NDD-CKD; 0.30 g/dL and 0.34 g/dL for PD-CKD; and 0.18 g/dL and 0.90 g/dL for HD-CKD, respectively. Across all CKD subgroups, mean Hb levels increased after treatment with vadadustat in patients with baseline Hb levels < 10 g/dL.
Conclusion
In this interim analysis, we identified no new safety concerns beyond those outlined in the Japanese package insert for vadadustat, which is based on the results from pivotal clinical trials. The ongoing PMS will continue to offer valuable insights into the safety and effectiveness of vadadustat in real-world clinical practice.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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