The Lancet Haematology最新文献

{"title":"Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a double-blind, randomised, phase 3 trial","authors":"Jong Wook Lee, Morag Griffin, Jin Seok Kim, Lily Wong Lee Lee, Caroline Piatek, Jun-ichi Nishimura, Cynthia Carrillo Infante, Deepak Jain, Peng Liu, Gleb Filippov, Flore Sicre de Fontbrune, Antonio Risitano, Austin G Kulasekararaj","doi":"10.1016/s2352-3026(23)00315-0","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00315-0","url":null,"abstract":"<h3>Background</h3><p><span><span>Symptoms of anaemia due to clinically significant extravascular haemolysis can affect patients with paroxysmal nocturnal haemoglobinuria (PNH) treated with C5 inhibitors (ravulizumab or eculizumab). The aim of this study was to assess the efficacy and safety of danicopan (ALXN2040), an investigational, first-in-class, oral </span>complement factor D inhibitor, as add-on therapy to </span>ravulizumab<span><span> or eculizumab </span>in patients with PNH and clinically significant extravascular haemolysis.</span></p><h3>Methods</h3><p><span>ALPHA is an ongoing, international, phase 3, randomised, double-blind, placebo-controlled trial evaluating danicopan as add-on therapy to ravulizumab or eculizumab. Eligible patients were adults (age ≥18 years) with PNH and clinically significant extravascular haemolysis (haemoglobin ≤9·5 g/dL; absolute reticulocyte count ≥120 × 10</span>⁹<span><span>/L) on ravulizumab or eculizumab for at least 6 months. Patients were randomly assigned (2:1) to danicopan or placebo added to ravulizumab or eculizumab for 12 weeks using an interactive response technology system. Randomisation was stratified based on transfusion history, haemoglobin, and patients enrolled from Japan. The initial oral danicopan dose was 150 mg three times a day; escalation to 200 mg three times a day was permitted based on clinical response. The infusion dose level of eculizumab (every 2 weeks) ranged from 900 mg to 1500 mg, and for ravulizumab (monthly or every 8 weeks) ranged from 3000 mg to 3600 mg. The primary endpoint was change in haemoglobin concentration from baseline to week 12. Here we present the protocol-prespecified interim analysis, planned when approximately 75% of participants were randomly assigned to </span>treatment and completed or discontinued at 12 weeks. This trial is registered with </span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"8px\" viewbox=\"0 0 8 8\" width=\"8px\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg> (<span>NCT04469465</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"8px\" viewbox=\"0 0 8 8\" width=\"8px\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg>).</p><h3>Findings</h3><p><span><span>Individuals were randomly assigned between Dec 16, 2020, and Aug 29, 2022. At data cutoff (June 28, 2022), 73 individuals were randomly assigned, received treatment, and were analysed for safety (danicopan, n=49; placebo, n=24). The protocol-prespecified interim efficacy analysis set included the first 63 participants (danicopan, n=42; placebo, n=21). At week 12, danicopan plus ravulizumab or eculizumab increased haemoglobin versus placebo plus ravulizumab or eculizumab (least squares mean [LSM] change from baseline: danicopan, 2·94 g/dL [95% CI 2·52 to 3·36]; placebo, 0·50 g/dL [–0·13 to","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"48 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138455936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Life after sickle cell disease, is it really uhuru?","authors":"Lydia H Pecker, Adeseye M Akinsete, C Patrick Carroll, Sophie Lanzkron, Kevin H M Kuo, Monica Hulbert, Elizabeth Stenger, Deepika S Darbari","doi":"10.1016/s2352-3026(23)00306-x","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00306-x","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"48 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138455937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving haematological care for adolescents","authors":"","doi":"10.1016/s2352-3026(23)00341-1","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00341-1","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138455940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of darbepoetin alfa in haemolytic disease of the fetus and newborn","authors":"Ravi M Patel, Robin Ohls","doi":"10.1016/s2352-3026(23)00316-2","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00316-2","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"48 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138455938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}