Pub Date : 2025-11-01DOI: 10.1016/S2352-3026(25)00264-9
Ruben Mesa, Harinder Gill, Lei Zhang, Jie Jin, Keita Kirito, Norio Komatsu, Albert Qin, Zhijian Xiao, Tsewang Tashi, Kazuya Shimoda, Kohshi Ohishi, Suning Chen, Xuelan Zuo, Shuichi Shirane, Yu Hu, Sujiang Zhang, Yi Wang, Katsuto Takenaka, Michiko Ichii, Na Xu, Lee-Yung Shih, Ken-Hong Lim, Sung-Eun Lee, Sung Hwa Bae, Winnie Z Y Teo, Dawn Maze, Stephen T Oh, Prithviraj Bose, Toshiaki Sato, Oleh Zagrijtschuk, Sheena Lin, Weichung Joe Shih, John Mascarenhas, Lucia Masarova
<p><strong>Background: </strong>The initial therapy for high-risk essential thrombocythaemia is usually hydroxyurea, but about a third of patients develop intolerance or resistance. A standard second-line agent has been anagrelide. Ropeginterferon alfa-2b, a new-generation interferon-based therapy, is approved for polycythaemia vera. We aimed to assess efficacy and safety of ropeginterferon alfa-2b compared with anagrelide in patients with essential thrombocythaemia with leukocytosis who are intolerant or resistant to hydroxyurea.</p><p><strong>Methods: </strong>The SURPASS ET open-label, randomised, active-controlled, phase 3 trial was done at 55 clinical sites across China, Japan, Taiwan, Hong Kong, South Korea, the USA, Singapore, and Canada and enrolled patients aged 18 years and older with high-risk (age >60 years with JAK2 Val617Phe or a history of disease-related thrombosis or haemorrhage), hydroxyurea-intolerant or hydroxyurea-resistant essential thrombocythaemia and white blood cell (WBC) count greater than 10 × 10<sup>9</sup> cells/L. Patients were randomly assigned (1:1) to ropeginterferon alfa-2b or anagrelide, stratified by platelet count, symptom score, and country. Ropeginterferon alfa-2b was subcutaneously dosed every 2 weeks, initially at 250 μg, then titrated to 350 μg at week 2, and to 500 μg from week 4 onward. Anagrelide was orally dosed according to the US Food and Drug Administration-approved prescribing information. The primary endpoint was the rate of response at months 9 and 12, as per modified European LeukemiaNet (ELN) criteria. The main planned analysis for the study was done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT04285086 and is completed, and an extension study for collecting long-term data is ongoing.</p><p><strong>Findings: </strong>Between Aug 25, 2020, and Nov 12, 2024, 245 patients were screened and 174 were randomly assigned (91 to ropeginterferon alfa-2b and 83 to anagrelide). The median follow-up was 12·5 months (IQR 11·5-12·9). At baseline, 47 (52%) of 91 participants in the ropeginterferon alfa-2b group and 44 (53%) of 83 participants in the anagrelide group were female. 167 (96%) of 174 participants were Asian and seven (4%) were White. The trial met its primary endpoint, with 39 (43%) of 91 participants in the ropeginterferon alfa-2b group showing durable modified ELN criteria responses at months 9 and 12, compared with five (6%) of 83 participants in the anagrelide group. This difference (36·5%, 95% CI 25·4-47·7) was significant (p=0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 27 (34%) of 80 patients in the anagrelide group and 21 (23%) of 91 patients in the ropeginterferon alfa-2b group. In the ropeginterferon alfa-2b group, the most common grade 3 or worse adverse events were infections and infestations, occurring eight (9%) of 91 patients, compared with five (6%) of 80 patients in the anagrelide group. In the anagrelide group,
{"title":"Ropeginterferon alfa-2b in hydroxyurea-intolerant or hydroxyurea-refractory essential thrombocythaemia (SURPASS ET): a multicentre, open-label, randomised, active-controlled, phase 3 study.","authors":"Ruben Mesa, Harinder Gill, Lei Zhang, Jie Jin, Keita Kirito, Norio Komatsu, Albert Qin, Zhijian Xiao, Tsewang Tashi, Kazuya Shimoda, Kohshi Ohishi, Suning Chen, Xuelan Zuo, Shuichi Shirane, Yu Hu, Sujiang Zhang, Yi Wang, Katsuto Takenaka, Michiko Ichii, Na Xu, Lee-Yung Shih, Ken-Hong Lim, Sung-Eun Lee, Sung Hwa Bae, Winnie Z Y Teo, Dawn Maze, Stephen T Oh, Prithviraj Bose, Toshiaki Sato, Oleh Zagrijtschuk, Sheena Lin, Weichung Joe Shih, John Mascarenhas, Lucia Masarova","doi":"10.1016/S2352-3026(25)00264-9","DOIUrl":"10.1016/S2352-3026(25)00264-9","url":null,"abstract":"<p><strong>Background: </strong>The initial therapy for high-risk essential thrombocythaemia is usually hydroxyurea, but about a third of patients develop intolerance or resistance. A standard second-line agent has been anagrelide. Ropeginterferon alfa-2b, a new-generation interferon-based therapy, is approved for polycythaemia vera. We aimed to assess efficacy and safety of ropeginterferon alfa-2b compared with anagrelide in patients with essential thrombocythaemia with leukocytosis who are intolerant or resistant to hydroxyurea.</p><p><strong>Methods: </strong>The SURPASS ET open-label, randomised, active-controlled, phase 3 trial was done at 55 clinical sites across China, Japan, Taiwan, Hong Kong, South Korea, the USA, Singapore, and Canada and enrolled patients aged 18 years and older with high-risk (age >60 years with JAK2 Val617Phe or a history of disease-related thrombosis or haemorrhage), hydroxyurea-intolerant or hydroxyurea-resistant essential thrombocythaemia and white blood cell (WBC) count greater than 10 × 10<sup>9</sup> cells/L. Patients were randomly assigned (1:1) to ropeginterferon alfa-2b or anagrelide, stratified by platelet count, symptom score, and country. Ropeginterferon alfa-2b was subcutaneously dosed every 2 weeks, initially at 250 μg, then titrated to 350 μg at week 2, and to 500 μg from week 4 onward. Anagrelide was orally dosed according to the US Food and Drug Administration-approved prescribing information. The primary endpoint was the rate of response at months 9 and 12, as per modified European LeukemiaNet (ELN) criteria. The main planned analysis for the study was done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT04285086 and is completed, and an extension study for collecting long-term data is ongoing.</p><p><strong>Findings: </strong>Between Aug 25, 2020, and Nov 12, 2024, 245 patients were screened and 174 were randomly assigned (91 to ropeginterferon alfa-2b and 83 to anagrelide). The median follow-up was 12·5 months (IQR 11·5-12·9). At baseline, 47 (52%) of 91 participants in the ropeginterferon alfa-2b group and 44 (53%) of 83 participants in the anagrelide group were female. 167 (96%) of 174 participants were Asian and seven (4%) were White. The trial met its primary endpoint, with 39 (43%) of 91 participants in the ropeginterferon alfa-2b group showing durable modified ELN criteria responses at months 9 and 12, compared with five (6%) of 83 participants in the anagrelide group. This difference (36·5%, 95% CI 25·4-47·7) was significant (p=0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 27 (34%) of 80 patients in the anagrelide group and 21 (23%) of 91 patients in the ropeginterferon alfa-2b group. In the ropeginterferon alfa-2b group, the most common grade 3 or worse adverse events were infections and infestations, occurring eight (9%) of 91 patients, compared with five (6%) of 80 patients in the anagrelide group. In the anagrelide group,","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 11","pages":"e862-e875"},"PeriodicalIF":17.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/S2352-3026(25)00262-5
Omid Seidizadeh, Ferdows Atiq, Nathan T Connell, Parnian Alavi, Giancarlo Castaman, David Lillicrap, Flora Peyvandi
The global population is ageing and this demographic shift has profound effects on haemostasis, notably a progressive tilt towards a hypercoagulable state. A major age-associated change in haemostasis is the increase in von Willebrand factor (VWF), a plasma glycoprotein essential for primary and secondary haemostasis. VWF deficiency causes von Willebrand disease, which is the most common inherited bleeding disorder and affects approximately 1% of the population. Conversely, elevated VWF concentrations are linked to increased thrombotic risk; VWF concentrations increase with age by approximately 10-15 IU/dL per decade. Moreover, longitudinal data indicate that VWF concentrations might normalise over time in individuals initially diagnosed with von Willebrand disease. Understanding the mechanisms underlying age-related increases in VWF is crucial for refining the disease classification and optimising management. Given the strong association between VWF, coagulation factor VIII (which is stabilised and transported by VWF), and thrombotic risk, the interplay between ageing and VWF dynamics has clinical implications. This Review examines age-related changes in VWF synthesis, storage, multimeric structure, and clearance. We also discuss the consequences of rising VWF concentrations in older adults on bleeding symptoms, von Willebrand disease diagnosis and management, and the related risks of thrombosis and cardiovascular complications. Finally, we identify essential knowledge gaps and outline priorities for future research and clinical practice.
{"title":"Von Willebrand factor and von Willebrand disease in ageing: mechanisms, evolving phenotypes, and clinical implications.","authors":"Omid Seidizadeh, Ferdows Atiq, Nathan T Connell, Parnian Alavi, Giancarlo Castaman, David Lillicrap, Flora Peyvandi","doi":"10.1016/S2352-3026(25)00262-5","DOIUrl":"https://doi.org/10.1016/S2352-3026(25)00262-5","url":null,"abstract":"<p><p>The global population is ageing and this demographic shift has profound effects on haemostasis, notably a progressive tilt towards a hypercoagulable state. A major age-associated change in haemostasis is the increase in von Willebrand factor (VWF), a plasma glycoprotein essential for primary and secondary haemostasis. VWF deficiency causes von Willebrand disease, which is the most common inherited bleeding disorder and affects approximately 1% of the population. Conversely, elevated VWF concentrations are linked to increased thrombotic risk; VWF concentrations increase with age by approximately 10-15 IU/dL per decade. Moreover, longitudinal data indicate that VWF concentrations might normalise over time in individuals initially diagnosed with von Willebrand disease. Understanding the mechanisms underlying age-related increases in VWF is crucial for refining the disease classification and optimising management. Given the strong association between VWF, coagulation factor VIII (which is stabilised and transported by VWF), and thrombotic risk, the interplay between ageing and VWF dynamics has clinical implications. This Review examines age-related changes in VWF synthesis, storage, multimeric structure, and clearance. We also discuss the consequences of rising VWF concentrations in older adults on bleeding symptoms, von Willebrand disease diagnosis and management, and the related risks of thrombosis and cardiovascular complications. Finally, we identify essential knowledge gaps and outline priorities for future research and clinical practice.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 11","pages":"e908-e917"},"PeriodicalIF":17.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/S2352-3026(25)00286-8
Barbara Gianesin, Frédéric B Piel, Lucia de Franceschi, Gian Luca Forni
{"title":"Incorporating national disease burden in GBD estimates of haemoglobinopathies in Italy.","authors":"Barbara Gianesin, Frédéric B Piel, Lucia de Franceschi, Gian Luca Forni","doi":"10.1016/S2352-3026(25)00286-8","DOIUrl":"https://doi.org/10.1016/S2352-3026(25)00286-8","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 11","pages":"e857-e859"},"PeriodicalIF":17.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-08-26DOI: 10.1016/S2352-3026(25)00146-2
Sarah H Atkinson, Parminder S Suchdev, Michael Bode, Bianca Carducci, Carla Cerami, Martin N Mwangi, Sorrel Namaste, Pattanee Winichagoon, Sumie Leung, Agnes M Mutua, Kelvin Mokaya Abuga, Imelda Angeles-Agdeppa, Robin Blythe, Natalie Carvalho, Ana Cepeda-Lopez, James H Cross, Saskia de Pee, Erica Di Ruggiero, Jessica Fanzo, Ugo Gentilini, Wanjiku N Gichohi-Wainaina, Clare Glover-Wright, Filomena Gomes, Sonja Hess, Jacinta Holloway-Brown, Fatou Joof, Crystal Karakochuk, Nicholas J Kassebaum, Leila Larson, Sachith Mettananda, John Muthii Muriuki, Martha Mwangome, Eric O Ohuma, Victoria Oliver, Nandita Perumal, Kamija Phiri, Folake Samuel, Sheela Sinharoy, Tinashe Tizifa, Giorgia Valleriani, Kesso Gabrielle van Zutphen-Küffer, Florencia Vasta, Hans Verhoef, Yingying Wang, Kapil Yadav, Zhenyu Yang, Melissa Young, Michael B Zimmermann, Sant-Rayn Pasricha
{"title":"Getting back on track to meet global anaemia reduction targets: a Lancet Haematology Commission.","authors":"Sarah H Atkinson, Parminder S Suchdev, Michael Bode, Bianca Carducci, Carla Cerami, Martin N Mwangi, Sorrel Namaste, Pattanee Winichagoon, Sumie Leung, Agnes M Mutua, Kelvin Mokaya Abuga, Imelda Angeles-Agdeppa, Robin Blythe, Natalie Carvalho, Ana Cepeda-Lopez, James H Cross, Saskia de Pee, Erica Di Ruggiero, Jessica Fanzo, Ugo Gentilini, Wanjiku N Gichohi-Wainaina, Clare Glover-Wright, Filomena Gomes, Sonja Hess, Jacinta Holloway-Brown, Fatou Joof, Crystal Karakochuk, Nicholas J Kassebaum, Leila Larson, Sachith Mettananda, John Muthii Muriuki, Martha Mwangome, Eric O Ohuma, Victoria Oliver, Nandita Perumal, Kamija Phiri, Folake Samuel, Sheela Sinharoy, Tinashe Tizifa, Giorgia Valleriani, Kesso Gabrielle van Zutphen-Küffer, Florencia Vasta, Hans Verhoef, Yingying Wang, Kapil Yadav, Zhenyu Yang, Melissa Young, Michael B Zimmermann, Sant-Rayn Pasricha","doi":"10.1016/S2352-3026(25)00146-2","DOIUrl":"10.1016/S2352-3026(25)00146-2","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e717-e767"},"PeriodicalIF":17.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12774439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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