Sharon Van Nevel, Nan Zhang, Zhaofeng Xu, Manon Blauwblomme, Elke Vandewalle, Gabriele Holtappels, Natalie De Ruyck, Filip Van Nieuwerburgh, Stijn Vanhee, Philippe Gevaert, Claus Bachert
Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally characterized by tissue-infiltrating eosinophils. Various biologic treatments, targeting the inflammation, have demonstrated efficacy in reducing nasal polyp size and symptoms. However, their specific impact on granulocyte populations within polyps remains largely unclear. This study explores how different biological treatments modulate local nasal polyp inflammation by assessing changes in granulocyte presence and recruitment before and after treatment.
Methods
Type 2-high CRSwNP patients received treatment with mepolizumab, benralizumab, omalizumab, or dupilumab. Immunohistochemistry and protein measurements were performed on their nasal polyp tissue. Bulk RNA-sequencing was conducted on pre- and post-treatment nasal samples, identifying differentially expressed genes. These results were integrated with single-cell data from CRSwNP patients.
Results
Nasal polyp tissue from type 2-high patients exhibited substantial eosinophil infiltration and limited neutrophils present. All tested biologics reduced eosinophil-related proteins and genes in nasal tissue. However, our data suggest that benralizumab, mepolizumab and omalizumab could induce a concurrent upregulation of neutrophilic markers. In these patients, chemoattractant genes for neutrophils primarily originated from the epithelial cell cluster, whereas receptors for these biologics were expressed by plasma cells, dendritic cells, and mast cells.
Conclusion
Biological treatments effectively reduced eosinophilic inflammation in nasal polyps. However, most biologics could induce an eosinophil-to-neutrophil shift, indicating that solely targeting eosinophils may be insufficient as a treatment approach. Understanding these secondary effects on local immune pathways is critical for optimizing CRSwNP treatment strategies.
{"title":"Distinct Effects of Biological Treatments on Eosinophils and Neutrophils in Chronic Rhinosinusitis With Nasal Polyp Patients","authors":"Sharon Van Nevel, Nan Zhang, Zhaofeng Xu, Manon Blauwblomme, Elke Vandewalle, Gabriele Holtappels, Natalie De Ruyck, Filip Van Nieuwerburgh, Stijn Vanhee, Philippe Gevaert, Claus Bachert","doi":"10.1002/clt2.70117","DOIUrl":"https://doi.org/10.1002/clt2.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally characterized by tissue-infiltrating eosinophils. Various biologic treatments, targeting the inflammation, have demonstrated efficacy in reducing nasal polyp size and symptoms. However, their specific impact on granulocyte populations within polyps remains largely unclear. This study explores how different biological treatments modulate local nasal polyp inflammation by assessing changes in granulocyte presence and recruitment before and after treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Type 2-high CRSwNP patients received treatment with mepolizumab, benralizumab, omalizumab, or dupilumab. Immunohistochemistry and protein measurements were performed on their nasal polyp tissue. Bulk RNA-sequencing was conducted on pre- and post-treatment nasal samples, identifying differentially expressed genes. These results were integrated with single-cell data from CRSwNP patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nasal polyp tissue from type 2-high patients exhibited substantial eosinophil infiltration and limited neutrophils present. All tested biologics reduced eosinophil-related proteins and genes in nasal tissue. However, our data suggest that benralizumab, mepolizumab and omalizumab could induce a concurrent upregulation of neutrophilic markers. In these patients, chemoattractant genes for neutrophils primarily originated from the epithelial cell cluster, whereas receptors for these biologics were expressed by plasma cells, dendritic cells, and mast cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Biological treatments effectively reduced eosinophilic inflammation in nasal polyps. However, most biologics could induce an eosinophil-to-neutrophil shift, indicating that solely targeting eosinophils may be insufficient as a treatment approach. Understanding these secondary effects on local immune pathways is critical for optimizing CRSwNP treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Zhang, Yu Song, Xu Zhang, Jingyun Li, Zengxiao Zhang, Lin Xi, Luo Zhang, Yuan Zhang
Background
Nasal allergen challenge (NAC) is currently the only available test to confirm nasal responsiveness to allergens and is a core diagnostic tool for allergic rhinitis. NAC is currently diagnosed by combining existing subjective measures and objective assessment methods in pairs to assess outcomes, based on a strong positive result for a single item or a moderately positive result for a combination of two items. However, there are few data on the diagnostic outcomes and characteristics of its various diagnostic combinations.
Objective
To evaluate the differences and characteristics of various existing diagnostic methods (combinations of subjective and objective indicators) for NAC.
Method
During January 2023–December 2024, patients with history of chronic rhinitis (CR) who experienced nasal symptoms upon exposure to dust, as well as healthy controls, were enrolled. Demographic and clinical data were collected, followed by a NAC with Dermatophagoides farinae (Df). Total nasal symptom score (TNSS), visual analog scales (VAS), acoustic rhinometry (AcRh), Active anterior rhinomanometry (AAR) and 4-phase-rhinomanometry (4PR) were used for assessment before and after NAC. The diagnostic results, minimum NAC concentration at positive trigger, and type of positive response (subjective or objective) were recorded.
Result
A total of 180 patients and 133 healthy controls were enrolled in the study. Significant differences in positive rates were observed across the six diagnostic evaluation combinations (p = 0.001). The combination of subjective TNSS evaluation with objective AAR assessment demonstrated the highest positive rate among patients (55.6%), whereas the combination of subjective VAS evaluation with objective AcRh assessment yielded the lowest positive rate (31.7%). Furthermore, when diagnostic combinations triggered positive results, they favored strong objective positivity.
Conclusion
The diagnostic results derived from pairwise combinations of various subjective measurements and objective assessments exhibit variability, with objective assessments demonstrating a higher propensity to yield positive results compared to subjective measurements.
{"title":"Variability of Diagnostic Outcomes in Nasal Allergen Challenge: The Role of Combined Subjective and Objective Indicators","authors":"Yu Zhang, Yu Song, Xu Zhang, Jingyun Li, Zengxiao Zhang, Lin Xi, Luo Zhang, Yuan Zhang","doi":"10.1002/clt2.70124","DOIUrl":"10.1002/clt2.70124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nasal allergen challenge (NAC) is currently the only available test to confirm nasal responsiveness to allergens and is a core diagnostic tool for allergic rhinitis. NAC is currently diagnosed by combining existing subjective measures and objective assessment methods in pairs to assess outcomes, based on a strong positive result for a single item or a moderately positive result for a combination of two items. However, there are few data on the diagnostic outcomes and characteristics of its various diagnostic combinations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the differences and characteristics of various existing diagnostic methods (combinations of subjective and objective indicators) for NAC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>During January 2023–December 2024, patients with history of chronic rhinitis (CR) who experienced nasal symptoms upon exposure to dust, as well as healthy controls, were enrolled. Demographic and clinical data were collected, followed by a NAC with <i>Dermatophagoides farinae</i> (Df). Total nasal symptom score (TNSS), visual analog scales (VAS), acoustic rhinometry (AcRh), Active anterior rhinomanometry (AAR) and 4-phase-rhinomanometry (4PR) were used for assessment before and after NAC. The diagnostic results, minimum NAC concentration at positive trigger, and type of positive response (subjective or objective) were recorded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>A total of 180 patients and 133 healthy controls were enrolled in the study. Significant differences in positive rates were observed across the six diagnostic evaluation combinations (<i>p</i> = 0.001). The combination of subjective TNSS evaluation with objective AAR assessment demonstrated the highest positive rate among patients (55.6%), whereas the combination of subjective VAS evaluation with objective AcRh assessment yielded the lowest positive rate (31.7%). Furthermore, when diagnostic combinations triggered positive results, they favored strong objective positivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The diagnostic results derived from pairwise combinations of various subjective measurements and objective assessments exhibit variability, with objective assessments demonstrating a higher propensity to yield positive results compared to subjective measurements.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12628074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145547627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Zhao, Litao Zhang, Liming Wu, Bin Yang, Jinyan Wang, Yumei Li, Qingchun Diao, Jingyi Li, Qing Sun, Xiaohong Zhu, Xiaoyong Man, Lihua Wang, Yanyan Feng, Tao Cai, Huiming Zeng, Linfeng Li, Jianyun Lu, Hong Ren, Fuqiu Li, Qianjin Lu, Xiaohua Tao, Rong Xiao, Chao Ji, Wenjie Zhao, Wei Chu, Bo Chen, Jianzhong Zhang
<div> <section> <h3> Background</h3> <p>Atopic dermatitis (AD) often coexists with other type 2 inflammatory diseases. Stapokibart, a humanized IgG4 monoclonal antibody targeting interleukin-4 receptor alpha subunit, showed high efficacy and favorable safety in a phase 3 trial. This post-hoc analysis aimed to compare the efficacy and safety of stapokibart in AD patients with and without type 2 comorbidities.</p> </section> <section> <h3> Methods</h3> <p>During 16-week double-blind period, participants were randomly assigned to stapokibart 600 (loading dose)-300 mg (<i>n</i> = 251) or placebo (<i>n</i> = 249) treatment every other week (Q2W). All patients received stapokibart 300 mg Q2W during subsequent 36-week maintenance period. Patients with ≥ 1 of the following conditions were classified into comorbid subgroup: allergic rhinitis, asthma, food allergies, chronic urticaria, or chronic obstructive pulmonary disease. Post-hoc outcomes included response rates of ≥ 75%/90% improvement in Eczema Area and Severity Index score (EASI-75/90), Investigator's Global Assessment score of 0 or 1 (IGA 0/1) with ≥ 2-point reduction, and ≥ 4-point reduction in weekly average of daily peak pruritus numerical rating scale score (PP-NRS4), and the percentage change from baseline in weekly average of daily PP-NRS score. Treatment-emergent adverse events (TEAEs) were also analyzed by subgroups.</p> </section> <section> <h3> Results</h3> <p>Ninety-two patients (36.7%) in stapokibart group and 102 (41.0%) in placebo group had type 2 comorbidities. The demographic characteristics and baseline disease scores were generally comparable across four groups. At week 16, stapokibart demonstrated superior efficacy over placebo in patients with and without type 2 comorbidities. In patients with comorbidities, the response rates of EASI-75, IGA 0/1, and PP-NRS4 in stapokibart and placebo groups were 77.2% versus 26.5%, 55.4% versus 17.6%, and 43.5% versus 12.7%, respectively. In patients without comorbidities, these response rates were 61.0% versus 25.3%, 37.7% versus 15.1%, and 31.4% versus 11.0%, respectively (all <i>p</i> values < 0.0001). All patients showed further improvements in efficacy outcomes during weeks 20–52. TEAEs occurred in 88.8% and 87.7% of comorbid and non-comorbid patients over weeks 0–52. The incidence of conjunctivitis was 5.9% and 5.0%, respectively.</p> </section> <section> <h3> Conclusion</h3> <p>Stapokibart was effective and safe in adults with moderate-to-severe AD both with and without type 2 comorbidities in both short-term and long-term treatment.
{"title":"Efficacy and Safety of Stapokibart in Adults With Moderate-to-Severe Atopic Dermatitis With and Without Type 2 Comorbidities: A Post Hoc Analysis of a Phase 3 Trial","authors":"Yan Zhao, Litao Zhang, Liming Wu, Bin Yang, Jinyan Wang, Yumei Li, Qingchun Diao, Jingyi Li, Qing Sun, Xiaohong Zhu, Xiaoyong Man, Lihua Wang, Yanyan Feng, Tao Cai, Huiming Zeng, Linfeng Li, Jianyun Lu, Hong Ren, Fuqiu Li, Qianjin Lu, Xiaohua Tao, Rong Xiao, Chao Ji, Wenjie Zhao, Wei Chu, Bo Chen, Jianzhong Zhang","doi":"10.1002/clt2.70121","DOIUrl":"10.1002/clt2.70121","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Atopic dermatitis (AD) often coexists with other type 2 inflammatory diseases. Stapokibart, a humanized IgG4 monoclonal antibody targeting interleukin-4 receptor alpha subunit, showed high efficacy and favorable safety in a phase 3 trial. This post-hoc analysis aimed to compare the efficacy and safety of stapokibart in AD patients with and without type 2 comorbidities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>During 16-week double-blind period, participants were randomly assigned to stapokibart 600 (loading dose)-300 mg (<i>n</i> = 251) or placebo (<i>n</i> = 249) treatment every other week (Q2W). All patients received stapokibart 300 mg Q2W during subsequent 36-week maintenance period. Patients with ≥ 1 of the following conditions were classified into comorbid subgroup: allergic rhinitis, asthma, food allergies, chronic urticaria, or chronic obstructive pulmonary disease. Post-hoc outcomes included response rates of ≥ 75%/90% improvement in Eczema Area and Severity Index score (EASI-75/90), Investigator's Global Assessment score of 0 or 1 (IGA 0/1) with ≥ 2-point reduction, and ≥ 4-point reduction in weekly average of daily peak pruritus numerical rating scale score (PP-NRS4), and the percentage change from baseline in weekly average of daily PP-NRS score. Treatment-emergent adverse events (TEAEs) were also analyzed by subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ninety-two patients (36.7%) in stapokibart group and 102 (41.0%) in placebo group had type 2 comorbidities. The demographic characteristics and baseline disease scores were generally comparable across four groups. At week 16, stapokibart demonstrated superior efficacy over placebo in patients with and without type 2 comorbidities. In patients with comorbidities, the response rates of EASI-75, IGA 0/1, and PP-NRS4 in stapokibart and placebo groups were 77.2% versus 26.5%, 55.4% versus 17.6%, and 43.5% versus 12.7%, respectively. In patients without comorbidities, these response rates were 61.0% versus 25.3%, 37.7% versus 15.1%, and 31.4% versus 11.0%, respectively (all <i>p</i> values < 0.0001). All patients showed further improvements in efficacy outcomes during weeks 20–52. TEAEs occurred in 88.8% and 87.7% of comorbid and non-comorbid patients over weeks 0–52. The incidence of conjunctivitis was 5.9% and 5.0%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Stapokibart was effective and safe in adults with moderate-to-severe AD both with and without type 2 comorbidities in both short-term and long-term treatment.","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12628279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Skin is the largest organ of the human body, and acts as a fundamental barrier. Beyond its protective role, it serves as a key immune organ, mediating immune surveillance and regulation. Exposure to environmental factors such as mechanical trauma, detergents, air pollution, and microbial dysbiosis can compromise the skin barrier triggering the release of pro-inflammatory cytokines that contribute to the pathogenesis of allergic diseases including atopic dermatitis (AD). Nutrition profoundly impacts skin health, influencing cell proliferation, tissue repair, and immune functions.
Methods
This review aims to explore the relationship between diet and skin barrier function, with a specific focus on AD.
Results
The evidence on micro- and macronutrients, probiotics, and various dietary patterns, highlighting their potential to enhance or impair skin barrier integrity, provides a comprehensive exploration of how diet may serve as a modifiable factor in supporting skin health and preventing allergic diseases. This review also outlines directions for improving future research.
Conclusion
Diet is an important modifiable factor in preserving skin barrier integrity and may contribute to the prevention and management of AD. However, inconsistent evidence precludes definitive dietary recommendations, highlighting the need for further research.
{"title":"Feeding the Skin Barrier: The Impact of Macro- and Micronutrients on Skin Barrier Function","authors":"Klaudia Ryczaj, Burcin Beken, Cezmi Akdis","doi":"10.1002/clt2.70105","DOIUrl":"10.1002/clt2.70105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Skin is the largest organ of the human body, and acts as a fundamental barrier. Beyond its protective role, it serves as a key immune organ, mediating immune surveillance and regulation. Exposure to environmental factors such as mechanical trauma, detergents, air pollution, and microbial dysbiosis can compromise the skin barrier triggering the release of pro-inflammatory cytokines that contribute to the pathogenesis of allergic diseases including atopic dermatitis (AD). Nutrition profoundly impacts skin health, influencing cell proliferation, tissue repair, and immune functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review aims to explore the relationship between diet and skin barrier function, with a specific focus on AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The evidence on micro- and macronutrients, probiotics, and various dietary patterns, highlighting their potential to enhance or impair skin barrier integrity, provides a comprehensive exploration of how diet may serve as a modifiable factor in supporting skin health and preventing allergic diseases. This review also outlines directions for improving future research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Diet is an important modifiable factor in preserving skin barrier integrity and may contribute to the prevention and management of AD. However, inconsistent evidence precludes definitive dietary recommendations, highlighting the need for further research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12626168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan A. Bernstein, Emel Aygören-Pürsün, Mauro Cancian, Danny M. Cohn, Timothy Craig, Vesna Grivcheva-Panovska, Anthony Jordan, William R. Lumry, Inmaculada Martinez-Saguer, Isaac Melamed, Kazumasa Ohmura, Jonny Peter, Marc A. Riedl, Daniel F. Soteres, Petra Staubach, Marcin Stobiecki, Ya-Hsiu Chuang, Michael D. Smith, Christopher M. Yea, Paul K. Audhya, Andrea Zanichelli, Henriette Farkas
Background
Hereditary angioedema (HAE-C1INH) attacks involving mucosal tissue may progress rapidly and often lead to substantial morbidity. Severe laryngeal attacks can be fatal without prompt administration of on-demand treatment. This prespecified interim analysis evaluated the safety and effectiveness of sebetralstat in laryngeal and abdominal attacks in the ongoing, 2-year, open-label extension KONFIDENT-S study (NCT05505916).
Methods
Eligible participants ≥ 12 years with HAE-C1INH self-administered sebetralstat 600 mg film-coated tablets with an optional second dose after 3 h, if warranted. Primary outcome: incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes: times to beginning of symptom relief, reduction in severity, and complete resolution.
Results
At data cutoff (Sep 14, 2024), 32 laryngeal (16 participants) and 533 abdominal only attacks (102 participants) were treated with sebetralstat. Seven (43.8%) participants with laryngeal attacks experienced 14 TEAEs whereas 36 (35.3%) participants with abdominal attacks experienced 91 TEAEs. No difficulty swallowing sebetralstat was reported. Median (IQR) time to treatment: 11.5 min (1.0–34.0) and 20.0 min (1.0–61.0) for laryngeal and abdominal attacks, respectively; time to beginning of symptom relief: 1.29 h (0.76–3.02) and 1.27 h (0.76–3.54); reduction in attack severity: 4.25 h (1.22 to > 12) and 3.52 h (1.26 to > 12); complete attack resolution: 12.69 h (5.11 to > 24) and 15.17 h (4.46 to > 24). Most mucosal attacks that achieved beginning of symptom relief within 12 h did so with a single dose of sebetralstat (laryngeal: 96.0%; abdominal: 95.8%). Conventional on-demand treatment was administered within 12 h for 3 (9.4%) laryngeal and 43 (8.1%) abdominal attacks.
Conclusion
Oral sebetralstat enabled rapid treatment of laryngeal and abdominal attacks of all severities, was well tolerated, and provided early symptom relief.
背景：遗传性血管性水肿（HAE-C1INH）累及粘膜组织的发作可能进展迅速，并经常导致严重的发病率。如果不及时按需治疗，严重的喉部发作可能是致命的。这项预先指定的中期分析在正在进行的为期2年的开放标签扩展KONFIDENT-S研究（NCT05505916）中评估了sebetralstat在喉和腹部发作中的安全性和有效性。方法：符合条件的受试者≥12年，HAE-C1INH患者自行给药sebetralstat 600 mg薄膜包衣片，如果有必要，3小时后可选择第二次给药。主要结局：治疗发生不良事件（teae）的发生率。次要结局：症状开始缓解的时间，严重程度的减轻，和完全解决。结果：在数据截止时（2024年9月14日），32例喉部发作（16例）和533例腹部发作（102例）接受了sebetralstat治疗。7名（43.8%）喉部发作的参与者经历了14次teae，而36名（35.3%）腹部发作的参与者经历了91次teae。未见吞咽sebetralstat困难。治疗的中位（IQR）时间：喉部和腹部发作分别为11.5 min（1.0-34.0）和20.0 min (1.0-61.0)；至症状开始缓解时间：1.29 h（0.76-3.02）、1.27 h (0.76-3.54)；攻击严重程度降低：4.25小时（1.22至> 12）和3.52小时（1.26至> 12）；完全攻击分辨率：12.69小时（5.11至> 24）和15.17小时（4.46至> 24）。大多数在12小时内实现症状开始缓解的粘膜发作是通过单剂量的sebetralstat实现的（喉：96.0%；腹部：95.8%）。3例（9.4%）喉部发作和43例（8.1%）腹部发作在12小时内给予常规按需治疗。结论：口服sebetralstat可快速治疗各种严重程度的喉部和腹部发作，耐受性良好，并能早期缓解症状。
{"title":"Sebetralstat for On-Demand Treatment of Mucosal Hereditary Angioedema Attacks in KONFIDENT-S","authors":"Jonathan A. Bernstein, Emel Aygören-Pürsün, Mauro Cancian, Danny M. Cohn, Timothy Craig, Vesna Grivcheva-Panovska, Anthony Jordan, William R. Lumry, Inmaculada Martinez-Saguer, Isaac Melamed, Kazumasa Ohmura, Jonny Peter, Marc A. Riedl, Daniel F. Soteres, Petra Staubach, Marcin Stobiecki, Ya-Hsiu Chuang, Michael D. Smith, Christopher M. Yea, Paul K. Audhya, Andrea Zanichelli, Henriette Farkas","doi":"10.1002/clt2.70118","DOIUrl":"10.1002/clt2.70118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary angioedema (HAE-C1INH) attacks involving mucosal tissue may progress rapidly and often lead to substantial morbidity. Severe laryngeal attacks can be fatal without prompt administration of on-demand treatment. This prespecified interim analysis evaluated the safety and effectiveness of sebetralstat in laryngeal and abdominal attacks in the ongoing, 2-year, open-label extension KONFIDENT-S study (NCT05505916).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eligible participants ≥ 12 years with HAE-C1INH self-administered sebetralstat 600 mg film-coated tablets with an optional second dose after 3 h, if warranted. Primary outcome: incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes: times to beginning of symptom relief, reduction in severity, and complete resolution.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At data cutoff (Sep 14, 2024), 32 laryngeal (16 participants) and 533 abdominal only attacks (102 participants) were treated with sebetralstat. Seven (43.8%) participants with laryngeal attacks experienced 14 TEAEs whereas 36 (35.3%) participants with abdominal attacks experienced 91 TEAEs. No difficulty swallowing sebetralstat was reported. Median (IQR) time to treatment: 11.5 min (1.0–34.0) and 20.0 min (1.0–61.0) for laryngeal and abdominal attacks, respectively; time to beginning of symptom relief: 1.29 h (0.76–3.02) and 1.27 h (0.76–3.54); reduction in attack severity: 4.25 h (1.22 to > 12) and 3.52 h (1.26 to > 12); complete attack resolution: 12.69 h (5.11 to > 24) and 15.17 h (4.46 to > 24). Most mucosal attacks that achieved beginning of symptom relief within 12 h did so with a single dose of sebetralstat (laryngeal: 96.0%; abdominal: 95.8%). Conventional on-demand treatment was administered within 12 h for 3 (9.4%) laryngeal and 43 (8.1%) abdominal attacks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Oral sebetralstat enabled rapid treatment of laryngeal and abdominal attacks of all severities, was well tolerated, and provided early symptom relief.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12626162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hugo Viegas, Bernardo Sousa-Pinto, Rafael José Vieira, Aiste Ramanauskaite, Ellen Witte-Händel, Ana Gimenez-Arnau, Carole Guillet, Claudio Alberto Salvador Parisi, Constance Katelaris, Daria Fomina, Désirée Larenas-Linnemann, Jorge Sánchez, Elizabeth Garcia, Hermenio Lima, Igor Kaidashev, Iman Nasr, Isabel Ogueta Canales, Ivan Cherrez-Ojeda, Jean Bousquet, Jonathan A. Bernstein, Jonny Peter, Jose Ignacio Larco Sousa, Kanokvalai Kulthanan, Karsten Weller, Kiran Godse, Krzysztof Rutkowski, Lasma Lapina, Laurence Bouillet, Luis Felipe Ensina, Margarida Gonçalo, Maria Staevska, Mariam Ali Yousuf Al-Nesf, Markus Magerl, Martin Metz, Martijn van Doorn, Mary Anne Castor, Maryam Khoshkhui, Michael Makris, Michihiro Hide, Mohamad Abuzakouk, Mona Al-Ahmad, Murat Türk, Natasa Teovska Mitrevska, Niall Conlon, Nicole Nojarov, Pavel Kolkhir, Philip Li, Ramzy Mohammed Ali, Rand Arnaout, Riccardo Asero, Sabine Altrichter, Simon Francis Thomsen, Young-Min Ye, Zenon Brzoza, Zuotao Zhao, Torsten Zuberbier, Frank Siebenhaar, Emek Kocatürk, Sophia Neisinger
Background
Mobile health technologies may improve the management of chronic diseases, such as chronic spontaneous urticaria. However, effectiveness of mHealth tools largely depends on patient adherence, which can be influenced by various demographic, clinical, behavioural, psychosocial factors, and apps characteristics (appealing and simplicity of use). Understanding these adherence patterns is crucial for optimizing mHealth interventions. In this study, we aimed to assess adherence patterns associated to the use of CRUSE, a mHealth app designed for patients with CSU.
Methods
We assessed users of the CRUSE app with self-reported CSU or suggested by a physician. For each user, we evaluated the number of days they completed the CRUSE daily monitoring questionnaire (app adherence) within the first 3 months after installation. We constructed univariable and multivariable ordered beta regression models to identify predictors of 3-month adherence to the app.
Results
We analysed data from 2085 patients (66,114 days). Median adherence to the CRUSE app was of 22 days (24.4% of 90 days). In multivariable regression models, the variables more strongly associated with increased adherence to CRUSE included age (average increase = 0.16 percent points [pp] per additional year; 95% credible interval [CrI] = 0.08; 0.23 pp), male sex (average difference = 4.24 pp; 95% CrI = 1.77; 6.39 pp), being from a European country (average difference = 2.66 pp; 95% CrI = 0.59; 5.19 pp), and using monoclonal antibodies (average difference = 4.60 pp; 95% CrI = 2.26; 6.65 pp).
Conclusions
Our findings suggest that age, male sex, residence in Europe, and the use of monoclonal antibodies are significant factors associated with increased adherence to the CRUSE app. These insights may help identify patient subgroups who would benefit most from mHealth support in managing CSU.
{"title":"Key Predictors of Adherence to a Mobile Health App for Managing Chronic Spontaneous Urticaria","authors":"Hugo Viegas, Bernardo Sousa-Pinto, Rafael José Vieira, Aiste Ramanauskaite, Ellen Witte-Händel, Ana Gimenez-Arnau, Carole Guillet, Claudio Alberto Salvador Parisi, Constance Katelaris, Daria Fomina, Désirée Larenas-Linnemann, Jorge Sánchez, Elizabeth Garcia, Hermenio Lima, Igor Kaidashev, Iman Nasr, Isabel Ogueta Canales, Ivan Cherrez-Ojeda, Jean Bousquet, Jonathan A. Bernstein, Jonny Peter, Jose Ignacio Larco Sousa, Kanokvalai Kulthanan, Karsten Weller, Kiran Godse, Krzysztof Rutkowski, Lasma Lapina, Laurence Bouillet, Luis Felipe Ensina, Margarida Gonçalo, Maria Staevska, Mariam Ali Yousuf Al-Nesf, Markus Magerl, Martin Metz, Martijn van Doorn, Mary Anne Castor, Maryam Khoshkhui, Michael Makris, Michihiro Hide, Mohamad Abuzakouk, Mona Al-Ahmad, Murat Türk, Natasa Teovska Mitrevska, Niall Conlon, Nicole Nojarov, Pavel Kolkhir, Philip Li, Ramzy Mohammed Ali, Rand Arnaout, Riccardo Asero, Sabine Altrichter, Simon Francis Thomsen, Young-Min Ye, Zenon Brzoza, Zuotao Zhao, Torsten Zuberbier, Frank Siebenhaar, Emek Kocatürk, Sophia Neisinger","doi":"10.1002/clt2.70110","DOIUrl":"10.1002/clt2.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mobile health technologies may improve the management of chronic diseases, such as chronic spontaneous urticaria. However, effectiveness of mHealth tools largely depends on patient adherence, which can be influenced by various demographic, clinical, behavioural, psychosocial factors, and apps characteristics (appealing and simplicity of use). Understanding these adherence patterns is crucial for optimizing mHealth interventions. In this study, we aimed to assess adherence patterns associated to the use of CRUSE, a mHealth app designed for patients with CSU.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed users of the CRUSE app with self-reported CSU or suggested by a physician. For each user, we evaluated the number of days they completed the CRUSE daily monitoring questionnaire (app adherence) within the first 3 months after installation. We constructed univariable and multivariable ordered beta regression models to identify predictors of 3-month adherence to the app.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analysed data from 2085 patients (66,114 days). Median adherence to the CRUSE app was of 22 days (24.4% of 90 days). In multivariable regression models, the variables more strongly associated with increased adherence to CRUSE included age (average increase = 0.16 percent points [pp] per additional year; 95% credible interval [CrI] = 0.08; 0.23 pp), male sex (average difference = 4.24 pp; 95% CrI = 1.77; 6.39 pp), being from a European country (average difference = 2.66 pp; 95% CrI = 0.59; 5.19 pp), and using monoclonal antibodies (average difference = 4.60 pp; 95% CrI = 2.26; 6.65 pp).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that age, male sex, residence in Europe, and the use of monoclonal antibodies are significant factors associated with increased adherence to the CRUSE app. These insights may help identify patient subgroups who would benefit most from mHealth support in managing CSU.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12619656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eunice Dias de Castro, Luís Miguel Cardoso, João Jácome de Castro, Manuel Branco Ferreira
Background
Danazol and other attenuated androgens (AAs) have been a cornerstone of Hereditary Angioedema (HAE) long-term prophylaxis (LTP) for decades, alongside intravenous plasma-derived C1INH (pdC1INH). Danazol's potential androgenic effects, however, present several limitations to its prescription and use. With the emergence of safer and more effective LTP drugs, guidelines are now shifting danazol to a second-line option. These changes in HAE therapy require a new framework to guide physicians in the appropriate use of danazol in HAE LTP.
Methods
This study aimed to develop a consensus on key aspects of danazol management, including discontinuation strategies, through a 2-round Delphi methodology. Statements were defined by a steering committee of both Endocrinology and Allergy and Clinical Immunology specialists, considering the available evidence. A panel of 23 experts in HAE management voted on the statements to reach a consensus.
Results
This process resulted in 46 recommendations for the prescription, monitoring, and discontinuation of danazol in LTP, proposing specific strategies for appropriate danazol use. A consensus was achieved on contraindications for danazol usage in LTP, detailed parameters for ongoing monitoring, and instructions for therapy adjustment considering treatment effect and using patient-reported outcomes. Furthermore, seven recommendations provide guidance on the increasingly relevant challenge of danazol discontinuation in HAE patients.
Conclusion
This Delphi study specifically addresses the gap in clinical guidance for danazol management in HAE patients. The resulting consensus document provides a valuable tool to aid the standardization of danazol discontinuation protocols and ensures that patients can access the safest and most effective treatment options available.
{"title":"Delphi Consensus on Attenuated Androgen Use for Long-Term Prophylaxis in Hereditary Angioedema: AURA Project","authors":"Eunice Dias de Castro, Luís Miguel Cardoso, João Jácome de Castro, Manuel Branco Ferreira","doi":"10.1002/clt2.70116","DOIUrl":"10.1002/clt2.70116","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Danazol and other attenuated androgens (AAs) have been a cornerstone of Hereditary Angioedema (HAE) long-term prophylaxis (LTP) for decades, alongside intravenous plasma-derived C1INH (pdC1INH). Danazol's potential androgenic effects, however, present several limitations to its prescription and use. With the emergence of safer and more effective LTP drugs, guidelines are now shifting danazol to a second-line option. These changes in HAE therapy require a new framework to guide physicians in the appropriate use of danazol in HAE LTP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study aimed to develop a consensus on key aspects of danazol management, including discontinuation strategies, through a 2-round Delphi methodology. Statements were defined by a steering committee of both Endocrinology and Allergy and Clinical Immunology specialists, considering the available evidence. A panel of 23 experts in HAE management voted on the statements to reach a consensus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This process resulted in 46 recommendations for the prescription, monitoring, and discontinuation of danazol in LTP, proposing specific strategies for appropriate danazol use. A consensus was achieved on contraindications for danazol usage in LTP, detailed parameters for ongoing monitoring, and instructions for therapy adjustment considering treatment effect and using patient-reported outcomes. Furthermore, seven recommendations provide guidance on the increasingly relevant challenge of danazol discontinuation in HAE patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This Delphi study specifically addresses the gap in clinical guidance for danazol management in HAE patients. The resulting consensus document provides a valuable tool to aid the standardization of danazol discontinuation protocols and ensures that patients can access the safest and most effective treatment options available.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12606019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jorge Sánchez, Gabriel Montoya, Ana Caraballo, María-Fernanda Ordoñez-Rubiano, Margarita Velasquez, Claudia Arenas, Julián Londoño, Elizabeth García
Background
Sexual health in patients with atopic dermatitis (AD) remains scarcely studied. Identifying the problematic of sexual health disorders (SHD) in AD and associated factors is important for the design and implementation of targeted interventions.
Objective
To describe the frequency of sexual health disorders (SHD) in AD patients, identify risk factors and assess whether improved AD control with pharmacotherapy is associated with changes in SHD.
Methods
We performed a prospective observational study in AD patients over 18 years of age. Participants completed a survey assessing clinical aspects of SHD and AD at baseline and 5–7 months after initiating specialists-recommended treatment. For AD severity evaluation we used SCORAD and POEM scales and for SHD we used SyDSF-AP, IFSF, and MGH-SFQ.
Results
A total of 221 AD patients were enrolled. At baseline, the frequency of SHD varied according to AD severity (SHD in severe AD 100%, in moderate AD 96%, and in mild AD 56%). Risk factors for SHD were AD severity (SCORAD OR 3.88 [95% CI 2.68–4.73], POEM OR 4.67 [95% CI 3.05–5.79]), skin area affected (OR 3.15 [95% CI 2.88–5.19]), and disease duration (OR 3.75 [95% CI 1.88–4.91]). Improved AD control through pharmacotherapy reduced SHD frequency in mild AD (relative reduction [RR]: −60%), moderate AD (RR: −41%), and severe AD (RR: −28%).
Conclusion
Atopic dermatitis was frequently associated with SHD even in mild forms of the disease. However, AD clinical control reduced the frequency of SHD, and consequently improving the quality of life of patients.
背景：特应性皮炎（AD）患者的性健康研究仍然很少。识别AD中的性健康障碍（SHD）问题及其相关因素对于设计和实施有针对性的干预措施非常重要。目的：描述AD患者性健康障碍（SHD）的频率，识别危险因素，并评估药物治疗改善AD控制是否与SHD的改变有关。方法：我们对18岁以上的AD患者进行了一项前瞻性观察研究。参与者完成了一项调查，评估SHD和AD在基线和开始专家推荐治疗后5-7个月的临床方面。对于AD的严重程度评估，我们使用SCORAD和POEM量表，对于SHD，我们使用SyDSF-AP， IFSF和MGH-SFQ量表。结果：共纳入221例AD患者。在基线时，SHD的频率根据AD的严重程度而变化（重度AD为100%，中度AD为96%，轻度AD为56%）。SHD的危险因素为AD严重程度（SCORAD OR 3.88 [95% CI 2.68-4.73], POEM OR 4.67 [95% CI 3.05-5.79]）、皮肤受影响面积（OR 3.15 [95% CI 2.88-5.19]）和疾病持续时间（OR 3.75 [95% CI 1.88-4.91]）。通过药物治疗改善AD控制可降低轻度AD（相对降低[RR]: -60%）、中度AD（相对降低[RR]: -41%）和重度AD（相对降低：-28%）的SHD频率。结论：特应性皮炎经常与SHD相关，即使是在轻度的疾病形式。然而，AD临床控制降低了SHD的发生频率，从而提高了患者的生活质量。
{"title":"Sexual Health in Atopic Dermatitis: Impact of Skin Clinical Control","authors":"Jorge Sánchez, Gabriel Montoya, Ana Caraballo, María-Fernanda Ordoñez-Rubiano, Margarita Velasquez, Claudia Arenas, Julián Londoño, Elizabeth García","doi":"10.1002/clt2.70115","DOIUrl":"10.1002/clt2.70115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sexual health in patients with atopic dermatitis (AD) remains scarcely studied. Identifying the problematic of sexual health disorders (SHD) in AD and associated factors is important for the design and implementation of targeted interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To describe the frequency of sexual health disorders (SHD) in AD patients, identify risk factors and assess whether improved AD control with pharmacotherapy is associated with changes in SHD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a prospective observational study in AD patients over 18 years of age. Participants completed a survey assessing clinical aspects of SHD and AD at baseline and 5–7 months after initiating specialists-recommended treatment. For AD severity evaluation we used SCORAD and POEM scales and for SHD we used SyDSF-AP, IFSF, and MGH-SFQ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 221 AD patients were enrolled. At baseline, the frequency of SHD varied according to AD severity (SHD in severe AD 100%, in moderate AD 96%, and in mild AD 56%). Risk factors for SHD were AD severity (SCORAD OR 3.88 [95% CI 2.68–4.73], POEM OR 4.67 [95% CI 3.05–5.79]), skin area affected (OR 3.15 [95% CI 2.88–5.19]), and disease duration (OR 3.75 [95% CI 1.88–4.91]). Improved AD control through pharmacotherapy reduced SHD frequency in mild AD (relative reduction [RR]: −60%), moderate AD (RR: −41%), and severe AD (RR: −28%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Atopic dermatitis was frequently associated with SHD even in mild forms of the disease. However, AD clinical control reduced the frequency of SHD, and consequently improving the quality of life of patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12596026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chen Zhang, Qianqian Zhang, Jiani Chen, Fuying Cheng, Yizhang Wang, Shirui Xue, Yufei Yang, Wenwen Guo, Juan Liu, Dehui Wang, Li Hu, Xicai Sun, Huan Wang, Quan Liu
Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) significantly impairs the quality of life, and disease control is now considered the primary treatment goal. Although patient-reported outcome measures (PROMs) such as the 22-item Sinonasal Outcome Test (SNOT-22) and CRS-PRO are widely used, their utility in predicting long-term postoperative disease control remains limited.
Methods
This prospective follow-up study aimed to evaluate postoperative recovery and identify the predictors of suboptimal disease control in patients with CRSwNP by integrating preoperative PROMs with objective clinical features. A total of 102 patients with CRSwNP undergoing functional endoscopic sinus surgery (FESS) were enrolled, of whom 89 completed at least 12 months of follow-up. Preoperative and postoperative PROMs were compared across disease control groups classified based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 criteria. Least absolute shrinkage and selection operator regression was applied to select objective clinical predictors, which were then combined with either CRS-PRO or SNOT-22 item scores to develop and compare the nine machine learning models. Model performance was assessed using area under the curve (AUC), decision curve analysis, sensitivity, specificity, and other metrics.
Results
Eosinophil and neutrophil counts were identified as key objective predictors of suboptimal disease control after FESS. Among all models, logistic regression incorporating CRS-PRO scores and selected clinical features achieved the best performance, yielding an AUC of 0.866, accuracy of 83.3%, sensitivity of 72.7%, specificity of 89.5%, and F1-score of 76.2%. This model demonstrated a strong discriminatory ability and potential utility in individualized clinical decision-making.
Conclusion
Integrating preoperative CRS-PRO item scores with selected objective clinical parameters enables the accurate prediction of suboptimal disease control in patients with CRSwNP following FESS. This approach supports personalized risk stratification and postoperative management strategies.
{"title":"Patient-Reported Outcome Measures as Predictive Tools for Disease Control in Chronic Rhinosinusitis With Nasal Polyps: A Prospective Study","authors":"Chen Zhang, Qianqian Zhang, Jiani Chen, Fuying Cheng, Yizhang Wang, Shirui Xue, Yufei Yang, Wenwen Guo, Juan Liu, Dehui Wang, Li Hu, Xicai Sun, Huan Wang, Quan Liu","doi":"10.1002/clt2.70119","DOIUrl":"10.1002/clt2.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic rhinosinusitis with nasal polyps (CRSwNP) significantly impairs the quality of life, and disease control is now considered the primary treatment goal. Although patient-reported outcome measures (PROMs) such as the 22-item Sinonasal Outcome Test (SNOT-22) and CRS-PRO are widely used, their utility in predicting long-term postoperative disease control remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective follow-up study aimed to evaluate postoperative recovery and identify the predictors of suboptimal disease control in patients with CRSwNP by integrating preoperative PROMs with objective clinical features. A total of 102 patients with CRSwNP undergoing functional endoscopic sinus surgery (FESS) were enrolled, of whom 89 completed at least 12 months of follow-up. Preoperative and postoperative PROMs were compared across disease control groups classified based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 criteria. Least absolute shrinkage and selection operator regression was applied to select objective clinical predictors, which were then combined with either CRS-PRO or SNOT-22 item scores to develop and compare the nine machine learning models. Model performance was assessed using area under the curve (AUC), decision curve analysis, sensitivity, specificity, and other metrics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eosinophil and neutrophil counts were identified as key objective predictors of suboptimal disease control after FESS. Among all models, logistic regression incorporating CRS-PRO scores and selected clinical features achieved the best performance, yielding an AUC of 0.866, accuracy of 83.3%, sensitivity of 72.7%, specificity of 89.5%, and F1-score of 76.2%. This model demonstrated a strong discriminatory ability and potential utility in individualized clinical decision-making.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Integrating preoperative CRS-PRO item scores with selected objective clinical parameters enables the accurate prediction of suboptimal disease control in patients with CRSwNP following FESS. This approach supports personalized risk stratification and postoperative management strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12584042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Direct comparative efficacy data for biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) remain limited, particularly for novel agents like tezepelumab, underscoring the need to identify optimal therapies for precision management.
Objective
To rank the comparative efficacy and safety of dupilumab, tezepelumab, omalizumab, and mepolizumab versus placebo for CRSwNP using network meta-analysis.
Methods
PubMed, Embase, Web of Science, and Cochrane Library were searched from inception through April 1, 2025. Randomized controlled trials (RCTs) in adults with CRSwNP comparing biologics against placebo were eligible. PRISMA-NMA guidelines were followed. GRADE methodology was employed for evidence certainty assessment. Two investigators independently extracted data. Fixed-effect model network meta-analysis was performed, with treatments ranked via surface under the cumulative ranking curve (SUCRA). The primary outcomes were Nasal Polyp Score (NPS) and safety metrics (proportion of participants with ≥ 1 adverse event). Secondary outcomes included Sino-Nasal Outcome Test-22 (SNOT-22), University of Pennsylvania Smell Identification Test (UPSIT), and Nasal Congestion Score (NCS).
Results
Thirteen RCTs (n = 2304) evaluating four biologics versus placebo were included. Compared to placebo, NPS was significantly improved by dupilumab (WMD: −2.16, 95% CI [−2.44, −1.89]), omalizumab (WMD: 1.25, 95% CI [−1.52, −0.97]), mepolizumab (WMD: 0.90, 95% CI [−1.19, −0.62]), and tezepelumab (WMD: −1.50, 95% CI [−1.81, −1.19]). Dupilumab ranked first in efficacy outcomes (NPS, SNOT-22, UPSIT, and NCS, SUCRA ≥ 0.900, respectively). Tezepelumab ranked second in NPS (SUCRA: 0.720) and UPSIT (SUCRA: 0.749), while omalizumab ranked first in safety (SUCRA of adverse events: 0.064). GRADE assessments indicated that the certainty of the evidence was predominantly high for these key efficacy comparisons.
Conclusions
Dupilumab demonstrated the highest efficacy and safety profile. Tezepelumab showed comparable efficacy in NPS with omalizumab.
{"title":"Which Is the Best Biologic for Nasal Polyps: An Updated Network Meta-Analysis","authors":"Xi Xu, Jinting Lin, Minting Luo, Qingwu Wu","doi":"10.1002/clt2.70114","DOIUrl":"https://doi.org/10.1002/clt2.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Direct comparative efficacy data for biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) remain limited, particularly for novel agents like tezepelumab, underscoring the need to identify optimal therapies for precision management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To rank the comparative efficacy and safety of dupilumab, tezepelumab, omalizumab, and mepolizumab versus placebo for CRSwNP using network meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed, Embase, Web of Science, and Cochrane Library were searched from inception through April 1, 2025. Randomized controlled trials (RCTs) in adults with CRSwNP comparing biologics against placebo were eligible. PRISMA-NMA guidelines were followed. GRADE methodology was employed for evidence certainty assessment. Two investigators independently extracted data. Fixed-effect model network meta-analysis was performed, with treatments ranked via surface under the cumulative ranking curve (SUCRA). The primary outcomes were Nasal Polyp Score (NPS) and safety metrics (proportion of participants with ≥ 1 adverse event). Secondary outcomes included Sino-Nasal Outcome Test-22 (SNOT-22), University of Pennsylvania Smell Identification Test (UPSIT), and Nasal Congestion Score (NCS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirteen RCTs (<i>n</i> = 2304) evaluating four biologics versus placebo were included. Compared to placebo, NPS was significantly improved by dupilumab (WMD: −2.16, 95% CI [−2.44, −1.89]), omalizumab (WMD: 1.25, 95% CI [−1.52, −0.97]), mepolizumab (WMD: 0.90, 95% CI [−1.19, −0.62]), and tezepelumab (WMD: −1.50, 95% CI [−1.81, −1.19]). Dupilumab ranked first in efficacy outcomes (NPS, SNOT-22, UPSIT, and NCS, SUCRA ≥ 0.900, respectively). Tezepelumab ranked second in NPS (SUCRA: 0.720) and UPSIT (SUCRA: 0.749), while omalizumab ranked first in safety (SUCRA of adverse events: 0.064). GRADE assessments indicated that the certainty of the evidence was predominantly high for these key efficacy comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Dupilumab demonstrated the highest efficacy and safety profile. Tezepelumab showed comparable efficacy in NPS with omalizumab.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 11","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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