Lancet Respiratory Medicine最新文献

{"title":"Vanzacaftor–tezacaftor–deutivacaftor for children aged 6–11 years with cystic fibrosis (RIDGELINE Trial VX21-121-105): an analysis from a single-arm, phase 3 trial","authors":"Jordana E Hoppe, Ajay S Kasi, Jessica E Pittman, Renee Jensen, Lena P Thia, Philip Robinson, Pornchai Tirakitsoontorn, Bonnie Ramsey, Marcus A Mall, Jennifer L Taylor-Cousar, Edward F McKone, Elizabeth Tullis, Danieli B Salinas, Jiaqiang Zhu, Yih-Chieh Chen, Violeta Rodriguez-Romero, Patrick R Sosnay, Gwyneth Davies","doi":"10.1016/s2213-2600(24)00407-7","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00407-7","url":null,"abstract":"<h3>Background</h3>In phase 2 trials in people with cystic fibrosis aged 18 years and older, vanzacaftor–tezacaftor–deutivacaftor has been shown to be a safe and effective, once-daily cystic fibrosis transmembrane conductance regulator (CFTR) modulator. Restoring normal CFTR function early in life has the potential to prevent manifestations of cystic fibrosis. We aimed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of vanzacaftor–tezacaftor–deutivacaftor in children with cystic fibrosis aged 6–11 years.<h3>Methods</h3>In this multicentre, single-arm, phase 3 trial (RIDGELINE Trial VX21-121-105), participants were enrolled across 33 clinical sites that care for children with cystic fibrosis in eight countries (Australia, France, Germany, Netherlands, Sweden, Switzerland, the UK, and the USA). Eligible participants were aged 6–11 years with at least one elexacaftor–tezacaftor–ivacaftor-responsive <em>CFTR</em> variant, FEV<sub>1</sub> % predicted of 60% or higher, and stable cystic fibrosis as determined by investigators. Before study treatment, participants were either on stable elexacaftor–tezacaftor–ivacaftor for at least 28 days before screening or received the combination for a 4-week run-in period. Participants then received vanzacaftor–tezacaftor–deutivacaftor (<40 kg bodyweight: vanzacaftor 12 mg, tezacaftor 60 mg, and deutivacaftor 150 mg orally as three fixed-dose combination tablets once daily; ≥40 kg bodyweight: vanzacaftor 20 mg, tezacaftor 100 mg, and deutivacaftor 250 mg orally as two fixed-dose combination tablets once daily (manufactured by Patheon Pharmaceuticals, Cincinnati, OH, USA) from day 1 for 24 weeks. The primary endpoint was safety and tolerability, as measured by adverse events, vital signs, clinical laboratory values, electrocardiograms, and pulse oximetry. Endpoints were analysed in all participants who received at least one dose of vanzacaftor–tezacaftor–deutivacaftor. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT05422222</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and evaluation of the 6–11-year-old cohort is complete.<h3>Findings</h3>Between Feb 6 and May 18, 2023, 83 children were screened, of whom five were not eligible, and 78 children aged 6-11 years received at least one dose of vanzacaftor–tezacaftor–deutivacaftor. Median age was 9·3 years (IQR 7·6–10·4), 34 (44%) of 78 participants were female, 44 (56%) were male, 71 (91%) were White, one (1%) was Black or African American, and one (1%) was of multiple races. The analysis for these data was completed on Dec 15, 2023. Median expos","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"34 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912110","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}

{"title":"Vanzacaftor–tezacaftor–deutivacaftor versus elexacaftor–tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials","authors":"Claire Keating, Lael M Yonker, François Vermeulen, Dario Prais, Rachel W Linnemann, Aaron Trimble, Tom Kotsimbos, Joel Mermis, Andrew T Braun, Mark O'Carroll, Sivagurunathan Sutharsan, Bonnie Ramsey, Marcus A Mall, Jennifer L Taylor-Cousar, Edward F McKone, Elizabeth Tullis, Tim Floreth, Peter Michelson, Patrick R Sosnay, Nitin Nair, Alexander Horsley","doi":"10.1016/s2213-2600(24)00411-9","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00411-9","url":null,"abstract":"<h3>Background</h3>The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor–tezacaftor–deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor–tezacaftor–deutivacaftor compared with standard of care elexacaftor–tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years and older.<h3>Methods</h3>In two randomised, active-controlled, double-blind, phase 3 trials, individuals aged 12 years and older with stable cystic fibrosis with <em>F508del</em>-minimal function (SKYLINE Trial VX20-121-102) or with <em>F508del-F508del, F508del</em>-residual function, <em>F508del</em>-gating, or elexacaftor–tezacaftor–ivacaftor-responsive-non-<em>F508del</em> genotypes (SKYLINE Trial VX20-121-103) were enrolled at 126 and 159 international sites, respectively. Eligible individuals were entered into a 4-week run-in period, during which they received elexacaftor (200 mg once daily), tezacaftor (100 mg once daily), and ivacaftor (150 mg once every 12 h) as two fixed-dose combination tablets in the morning and one ivacaftor tablet in the evening. They were then randomly assigned (1:1) to either elexacaftor (200 mg once daily), tezacaftor (100 mg once daily), and ivacaftor (150 mg once every 12 h) as two fixed-dose combination tablets in the morning and one ivacaftor tablet in the evening, or vanzacaftor (20 mg once daily), tezacaftor (100 mg once daily), and deutivacaftor (250 mg once daily) as two fixed-dose combination tablets in the morning, for the 52-week treatment period. All participants received matching placebo tablets to maintain the treatment blinding. Randomisation was done using an interactive web-response system and stratified by age, FEV<sub>1</sub> % predicted, sweat chloride concentration, and previous CFTR modulator use, and also by genotype for Trial VX20-121-103. The primary endpoint for both trials was absolute change in FEV<sub>1</sub> % predicted from baseline (most recent value before treatment on day 1) through week 24 (with non-inferiority of vanzacaftor–tezacaftor–deutivacaftor shown if the lower bound of the 95% CI for the primary endpoint was –3·0 or higher). Efficacy was assessed in all participants with the intended <em>CFTR</em> genotype who were randomly assigned to treatment and received at least one dose of study treatment during the treatment period. Safety was assessed in all participants who received at least one dose of study drug during the treatment period. These trials are registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"58 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912109","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}

{"title":"Navigating uncertainty: asthma biologics during pregnancy.","authors":"Imran Howell, Aleksandra Howell, Ian Pavord","doi":"10.1016/S2213-2600(24)00248-0","DOIUrl":"10.1016/S2213-2600(24)00248-0","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"10-11"},"PeriodicalIF":38.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114578","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}

{"title":"An international consensus on the use of asthma biologics in pregnancy.","authors":"Jennifer Naftel, David J Jackson, Matthew Coleman, Grainne d'Ancona, Liam G Heaney, Paddy Dennison, Apostolos Bossios, Hitasha Rupani","doi":"10.1016/S2213-2600(24)00174-7","DOIUrl":"10.1016/S2213-2600(24)00174-7","url":null,"abstract":"<p><p>Uncontrolled asthma is associated with an increased risk of adverse perinatal outcomes. Asthma biologics reduce exacerbation frequency, are steroid sparing, and improve quality of life in people with severe asthma. However, evidence for the use and safety of asthma biologics during pregnancy is scarce, largely because pregnant women were excluded from clinical trials. To help to support clinical teams, we conducted an international modified Delphi study. 141 panellists from 32 countries who were involved in the care of people with severe asthma completed two rounds of online surveys covering key areas surrounding the use of asthma biologics in pregnancy. The results from this international Delphi study emphasise risk versus benefit discussions and shared clinical decision making, with consensus among panellists that asthma biologics can be used during conception and throughout pregnancy, initiated during pregnancy in line with prescribing criteria for non-pregnant people, and initiated or continued during breastfeeding. Collating data through international registries remains essential to inform clinical guidelines.</p>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"80-91"},"PeriodicalIF":38.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114575","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}

{"title":"Collateral caring","authors":"Hemmings Wu","doi":"10.1016/s2213-2600(24)00421-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00421-1","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"46 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857696","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}

{"title":"The UK Tobacco and Vapes Bill: a historic opportunity","authors":"","doi":"10.1016/s2213-2600(24)00419-3","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00419-3","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"146 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849117","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}

{"title":"On the front lines of the sepsis crisis: hurdles faced by sepsis researchers, survivors, and family advocates","authors":"Jackie Duda","doi":"10.1016/s2213-2600(24)00420-x","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00420-x","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"42 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841168","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}

{"title":"Incorrect interpretation of the role of COVID-19 vaccination boosters in saving lives – Authors' reply","authors":"Margaux M I Meslé, Jeremy Brown, Marc-Alain Widdowson, Richard G Pebody","doi":"10.1016/s2213-2600(24)00363-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00363-1","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"148 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815920","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}

{"title":"Incorrect interpretation of the role of COVID-19 vaccination boosters in saving lives","authors":"Tijl De Bie","doi":"10.1016/s2213-2600(24)00334-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00334-5","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"35 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815921","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}

{"title":"Caring for our interlocutors on the threshold of life and death","authors":"Magdalena Zegarra Chiappori","doi":"10.1016/s2213-2600(24)00414-4","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00414-4","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"39 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804601","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}