Pub Date : 2025-01-10DOI: 10.1016/s2213-2600(24)00364-3
Jin-Fu Xu, Hui-Zhen Zheng, Hai-Wen Lu, Ling-Wei Wang, Bin Wu, Xiao-Dong Lv, Hong Luo, Jian Feng, Yuan-Yuan Li, Lin Liu, Jin-Guang Jia, Wei-Qiang Mo, Hong-Yan Gu, Jing-Bo Jiang, Dao-Xin Wang, Bin Wang, Li Li, Zhi Yuan, Wen Li, Min Xie, Min Zhang
<h3>Background</h3>Bronchiectasis is a disease with a global impact, but most published data come from high-income countries. We aimed to describe the clinical characteristics of patients with bronchiectasis in China.<h3>Methods</h3>The Chinese Bronchiectasis Registry (BE-China) is a prospective, observational cohort enrolling patients from 111 hospitals in China. Data on demographics, comorbidities, and aetiological testing results were collected from adult patients with bronchiectasis at baseline and annual follow-up. Patients who met the inclusion criteria (age ≥18 years; received chest high-resolution CT in the past year showing bronchiectasis affecting one or more lung lobes; and clinical history consistent with bronchiectasis, including chronic cough, daily sputum production, and history of exacerbations) were included. Patients with known cystic fibrosis were excluded. To investigate variations according to different economic regions, two groups were compared based on whether per capita disposable income of residents was greater than US$5553. Clinical characteristics were compared with the European (EMBARC) registry and other national registries.<h3>Findings</h3>Between Jan 10, 2020, and March 31, 2024, 10 324 patients from 97 centres were included in the study. Among 9501 participants with available data, the most common cause of bronchiectasis was post-infective disease (4101 [43·2%] patients), followed by idiopathic (2809 [29·6%] patients). 6676 (70·0%) of 9541 patients with available data had at least one exacerbation in the year before enrolment and 5427 (57·2%) of 9489 patients with available data were hospitalised at least once due to exacerbations. Treatments commonly used in high-income countries, such as inhaled antibiotics and macrolides, were infrequently used in China. Implementation of airway clearance in China was scarce, with only 1177 (12·2%) of 9647 patients having used at least one method of airway clearance. Compared with upper-middle-income regions, patients from lower-middle-income regions were younger (61·0 years [SD 14·0] <em>vs</em> 63·9 years [14·2]) with a higher proportion of pulmonary comorbidities (521 [17·8%] of 2922 patients <em>vs</em> 639 [8·6%] of 7402 with chronic obstructive pulmonary disease and 194 [6·6%] of 2922 patients <em>vs</em> 364 [4·9%] of 7402 patients with asthma), a higher tuberculosis burden (442 [16·0%] of 2768 patients <em>vs</em> 715 [10·6%] of 6733 patients), more severe radiological involvement (1160 [42·4%] of 2736 patients <em>vs</em> 2415 [35·4%] of 6816 patients with cystic bronchiectasis), more exacerbations (median 1·4 [IQR 0–2] in both groups; mean 1·4 [SD 1·6] <em>vs</em> 1·2 [1·4] in the previous year) and hospitalisations (1662 [60·6%] of 2743 patients <em>vs</em> 3765 [55·8%] of 6746 patients hospitalised at least once in the previous year), and poorer quality of life (median 57·4 [IQR 53·5–63·1] <em>vs</em> 58·7 [54·8–64·8] assessed by the Bronchiectasis Health Questionnai
{"title":"Baseline characteristics of patients in the Chinese Bronchiectasis Registry (BE-China): a multicentre prospective cohort study","authors":"Jin-Fu Xu, Hui-Zhen Zheng, Hai-Wen Lu, Ling-Wei Wang, Bin Wu, Xiao-Dong Lv, Hong Luo, Jian Feng, Yuan-Yuan Li, Lin Liu, Jin-Guang Jia, Wei-Qiang Mo, Hong-Yan Gu, Jing-Bo Jiang, Dao-Xin Wang, Bin Wang, Li Li, Zhi Yuan, Wen Li, Min Xie, Min Zhang","doi":"10.1016/s2213-2600(24)00364-3","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00364-3","url":null,"abstract":"<h3>Background</h3>Bronchiectasis is a disease with a global impact, but most published data come from high-income countries. We aimed to describe the clinical characteristics of patients with bronchiectasis in China.<h3>Methods</h3>The Chinese Bronchiectasis Registry (BE-China) is a prospective, observational cohort enrolling patients from 111 hospitals in China. Data on demographics, comorbidities, and aetiological testing results were collected from adult patients with bronchiectasis at baseline and annual follow-up. Patients who met the inclusion criteria (age ≥18 years; received chest high-resolution CT in the past year showing bronchiectasis affecting one or more lung lobes; and clinical history consistent with bronchiectasis, including chronic cough, daily sputum production, and history of exacerbations) were included. Patients with known cystic fibrosis were excluded. To investigate variations according to different economic regions, two groups were compared based on whether per capita disposable income of residents was greater than US$5553. Clinical characteristics were compared with the European (EMBARC) registry and other national registries.<h3>Findings</h3>Between Jan 10, 2020, and March 31, 2024, 10 324 patients from 97 centres were included in the study. Among 9501 participants with available data, the most common cause of bronchiectasis was post-infective disease (4101 [43·2%] patients), followed by idiopathic (2809 [29·6%] patients). 6676 (70·0%) of 9541 patients with available data had at least one exacerbation in the year before enrolment and 5427 (57·2%) of 9489 patients with available data were hospitalised at least once due to exacerbations. Treatments commonly used in high-income countries, such as inhaled antibiotics and macrolides, were infrequently used in China. Implementation of airway clearance in China was scarce, with only 1177 (12·2%) of 9647 patients having used at least one method of airway clearance. Compared with upper-middle-income regions, patients from lower-middle-income regions were younger (61·0 years [SD 14·0] <em>vs</em> 63·9 years [14·2]) with a higher proportion of pulmonary comorbidities (521 [17·8%] of 2922 patients <em>vs</em> 639 [8·6%] of 7402 with chronic obstructive pulmonary disease and 194 [6·6%] of 2922 patients <em>vs</em> 364 [4·9%] of 7402 patients with asthma), a higher tuberculosis burden (442 [16·0%] of 2768 patients <em>vs</em> 715 [10·6%] of 6733 patients), more severe radiological involvement (1160 [42·4%] of 2736 patients <em>vs</em> 2415 [35·4%] of 6816 patients with cystic bronchiectasis), more exacerbations (median 1·4 [IQR 0–2] in both groups; mean 1·4 [SD 1·6] <em>vs</em> 1·2 [1·4] in the previous year) and hospitalisations (1662 [60·6%] of 2743 patients <em>vs</em> 3765 [55·8%] of 6746 patients hospitalised at least once in the previous year), and poorer quality of life (median 57·4 [IQR 53·5–63·1] <em>vs</em> 58·7 [54·8–64·8] assessed by the Bronchiectasis Health Questionnai","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"82 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961670","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 : 2025-01-10DOI: 10.1016/s2213-2600(24)00427-2
Kevin W Southern
No Abstract
没有抽象的
{"title":"What does the expanding CFTR modulator programme mean for people with cystic fibrosis?","authors":"Kevin W Southern","doi":"10.1016/s2213-2600(24)00427-2","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00427-2","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"40 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961669","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 : 2025-01-09DOI: 10.1016/s2213-2600(24)00367-9
Sarah F Hak, Valérie D V Sankatsing, Joanne G Wildenbeest, Roderick P Venekamp, Beatrice Casini, Caterina Rizzo, Mathieu Bangert, Daan Van Brusselen, Elizabeth Button, María Garcés-Sánchez, César García Vera, Rolf Kramer, Simon de Lusignan, Marc Raes, Adam Meijer, John Paget, Jojanneke van Summeren
<h3>Background</h3>The majority of respiratory syncytial virus (RSV) infections in young children are managed in primary care, however, the disease burden in this setting remains poorly defined.<h3>Methods</h3>We did a prospective cohort study in primary care settings in Belgium, Italy, Spain, the Netherlands, and the UK during the RSV seasons of 2020–21 (UK only; from Jan 1, 2021), 2021–22, and 2022–23. Children aged younger than 5 years presenting to their general practitioner or primary care paediatrician with symptoms of an acute respiratory tract infection were eligible for RSV testing. Children who tested positive for RSV were consented and followed up for 30 days via a physician clinical report (initial primary care visit on day 1) and two parent-report questionnaires (days 14 and 30). We assessed the burden of RSV in terms of clinical course (symptoms, illness duration, and complications), health-care resource utilisation (primary care visits, emergency department visits, hospitalisation rate, and medication use), and societal impact (daycare or school absence and parental work absence) for the 30-day follow-up period.<h3>Findings</h3>Among 3414 tested children, 1124 (32·9%; 95% CI 31·3–34·5) tested positive for RSV. Among children with data on age, RSV positivity rate was 38·9% (36·1–41·7; n=466 of 1198) in children younger than 1 year and 25·9% (24·0–27·9; n=513 of 1979) in those aged 1 to <5 years. Of the 1124 RSV-positive children, 878 (78·1%) were enrolled and had day 1 data collected (median age 11·1 months [IQR 6·0–22·0]; 446 [50·9%] boys and 431 [49·1%] girls [N=877]). RSV illness lasted a mean of 11·7 days (95% CI 11·2–12·2; n=794). At day 14 and day 30, any remaining symptoms were reported in 451 of 804 (56·1% [95% CI 52·6–59·6]) and 261 of 724 (36·0% [32·6–39·7]) children. The mean number of primary care visits per child ranged from 1·4 (95% CI 1·2–1·6; the Netherlands) to 3·0 (2·8–3·3; Spain), and was higher in children younger than 1 year (2·7 visits [2·4–2·9]) than in those aged 1 to <5 years (2·1 [1·9–2·2]). Prescribed medication use varied, from 25 of 96 children (26·0% [95% CI 17·6–36·0]; the UK) to 228 of 297 children (76·8% [71·5–81·5]; Italy), with bronchodilators and antibiotics being the most commonly prescribed medicines across all countries. Prescribed medication use was reported in 258 of 418 children aged 1 to <5 years (61·7% [56·9–66·4]) and 196 of 394 children younger than 1 year (49·7% [44·7–54·8]). Missed working days by parents due to their child's RSV illness were reported in 340 of 744 cases (45·7% [42·1–49·4]); the mean number of missed workdays ranged from 1·3 days (95% CI 0·5–2·2) in Spain to 4·1 days (3·3–5·0) in Belgium.<h3>Interpretation</h3>RSV infections in children younger than 5 years in primary care are associated with substantial symptomatology, health-care utilisation, and parental work absence. Notable differences in RSV burden existed across countries, likely due to differences in p
{"title":"Burden of RSV infections among young children in primary care: a prospective cohort study in five European countries (2021–23)","authors":"Sarah F Hak, Valérie D V Sankatsing, Joanne G Wildenbeest, Roderick P Venekamp, Beatrice Casini, Caterina Rizzo, Mathieu Bangert, Daan Van Brusselen, Elizabeth Button, María Garcés-Sánchez, César García Vera, Rolf Kramer, Simon de Lusignan, Marc Raes, Adam Meijer, John Paget, Jojanneke van Summeren","doi":"10.1016/s2213-2600(24)00367-9","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00367-9","url":null,"abstract":"<h3>Background</h3>The majority of respiratory syncytial virus (RSV) infections in young children are managed in primary care, however, the disease burden in this setting remains poorly defined.<h3>Methods</h3>We did a prospective cohort study in primary care settings in Belgium, Italy, Spain, the Netherlands, and the UK during the RSV seasons of 2020–21 (UK only; from Jan 1, 2021), 2021–22, and 2022–23. Children aged younger than 5 years presenting to their general practitioner or primary care paediatrician with symptoms of an acute respiratory tract infection were eligible for RSV testing. Children who tested positive for RSV were consented and followed up for 30 days via a physician clinical report (initial primary care visit on day 1) and two parent-report questionnaires (days 14 and 30). We assessed the burden of RSV in terms of clinical course (symptoms, illness duration, and complications), health-care resource utilisation (primary care visits, emergency department visits, hospitalisation rate, and medication use), and societal impact (daycare or school absence and parental work absence) for the 30-day follow-up period.<h3>Findings</h3>Among 3414 tested children, 1124 (32·9%; 95% CI 31·3–34·5) tested positive for RSV. Among children with data on age, RSV positivity rate was 38·9% (36·1–41·7; n=466 of 1198) in children younger than 1 year and 25·9% (24·0–27·9; n=513 of 1979) in those aged 1 to <5 years. Of the 1124 RSV-positive children, 878 (78·1%) were enrolled and had day 1 data collected (median age 11·1 months [IQR 6·0–22·0]; 446 [50·9%] boys and 431 [49·1%] girls [N=877]). RSV illness lasted a mean of 11·7 days (95% CI 11·2–12·2; n=794). At day 14 and day 30, any remaining symptoms were reported in 451 of 804 (56·1% [95% CI 52·6–59·6]) and 261 of 724 (36·0% [32·6–39·7]) children. The mean number of primary care visits per child ranged from 1·4 (95% CI 1·2–1·6; the Netherlands) to 3·0 (2·8–3·3; Spain), and was higher in children younger than 1 year (2·7 visits [2·4–2·9]) than in those aged 1 to <5 years (2·1 [1·9–2·2]). Prescribed medication use varied, from 25 of 96 children (26·0% [95% CI 17·6–36·0]; the UK) to 228 of 297 children (76·8% [71·5–81·5]; Italy), with bronchodilators and antibiotics being the most commonly prescribed medicines across all countries. Prescribed medication use was reported in 258 of 418 children aged 1 to <5 years (61·7% [56·9–66·4]) and 196 of 394 children younger than 1 year (49·7% [44·7–54·8]). Missed working days by parents due to their child's RSV illness were reported in 340 of 744 cases (45·7% [42·1–49·4]); the mean number of missed workdays ranged from 1·3 days (95% CI 0·5–2·2) in Spain to 4·1 days (3·3–5·0) in Belgium.<h3>Interpretation</h3>RSV infections in children younger than 5 years in primary care are associated with substantial symptomatology, health-care utilisation, and parental work absence. Notable differences in RSV burden existed across countries, likely due to differences in p","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"6 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939528","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 : 2025-01-09DOI: 10.1016/s2213-2600(24)00402-8
Fatimah S Dawood, Meredith L McMorrow
No Abstract
没有抽象的
{"title":"Elucidating the outpatient burden of RSV disease in children","authors":"Fatimah S Dawood, Meredith L McMorrow","doi":"10.1016/s2213-2600(24)00402-8","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00402-8","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"24 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939506","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 : 2025-01-03DOI: 10.1016/s2213-2600(24)00371-0
Surya P Bhatt, Klaus F Rabe, Dave Singh, Mona Bafadhel, Claus F Vogelmeier
No Abstract
没有抽象的
{"title":"A response to therapy for COPD with dupilumab","authors":"Surya P Bhatt, Klaus F Rabe, Dave Singh, Mona Bafadhel, Claus F Vogelmeier","doi":"10.1016/s2213-2600(24)00371-0","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00371-0","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"97 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924527","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 : 2025-01-02DOI: 10.1016/s2213-2600(24)00407-7
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
<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
{"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}
Pub Date : 2025-01-02DOI: 10.1016/s2213-2600(24)00411-9
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
<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
{"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}
Pub Date : 2025-01-01Epub Date: 2024-08-28DOI: 10.1016/S2213-2600(24)00248-0
Imran Howell, Aleksandra Howell, Ian Pavord
{"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}
Pub Date : 2025-01-01Epub Date: 2024-08-28DOI: 10.1016/S2213-2600(24)00174-7
Jennifer Naftel, David J Jackson, Matthew Coleman, Grainne d'Ancona, Liam G Heaney, Paddy Dennison, Apostolos Bossios, Hitasha Rupani
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.
{"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}
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