Nuria Contreras, Andrea Escolar‐Peña, María I. Delgado‐Dolset, Paloma Fernández, David Obeso, Elena Izquierdo, Heleia González Cuervo, José Ángel Cumplido, Victoria Múgica, Carolina Cisneros, Santiago Angulo‐Díaz‐Parreño, Coral Barbas, Carlos Blanco, Teresa Carrillo, Domingo Barber, Alma Villaseñor, María M. Escribese
RationaleBiologics are becoming increasingly important in the management of severe asthma. However, little is known about the systemic immunometabolic consequences of Th2 response blockage.ObjectivesTo provide a better immunometabolic understanding of the effects of mepolizumab and omalizumab treatments by identifying potential biomarkers for monitoring.MethodsIn this exploratory longitudinal study severe asthmatic patients were followed for 18 months after initiating mepolizumab (n = 36) or Omalizumab (n = 20) treatment. Serum samples were collected before, 6, and 18 months after treatment. Targeted omic approaches were performed to analyze inflammatory metabolites (n = 35) and proteins (n = 45). Multiomic integration was performed individually for each treatment applying supervised analysis Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) framework. Then, potential biomarkers were confirmed using multivariate ROC analyses and correlated with clinical variables along treatment.Measurements and Main ResultsMepolizumab and omalizumab were both effective (improved clinical variables) and showed different and specific metabolic and protein profiles in severe asthmatic patients during treatment. Multiomic integration and multivariate ROC analyses identified specific biomarkers, such as arachidonic acid, palmitoleic acid, oleic acid, propionylcarnitine, bilirubin, CCL11, and TNFSF10, which can explain the differences observed with Mepolizumab treatment over 18 months and significantly correlate with clinical improvement. However, no significant biomolecules and no discriminative multivariate ROC curves were found for Omalizumab treatment.ConclusionsOur results provide a comprehensive insight into the differential effects of mepolizumab and omalizumab on the immunometabolic kinetics of the inflammatory response in severe asthma. We identified a set of biomolecules with potential for monitoring mepolizumab treatment which could be useful for personalized medicine.
{"title":"Multiomic Integration Analysis for Monitoring Severe Asthma Treated With Mepolizumab or Omalizumab","authors":"Nuria Contreras, Andrea Escolar‐Peña, María I. Delgado‐Dolset, Paloma Fernández, David Obeso, Elena Izquierdo, Heleia González Cuervo, José Ángel Cumplido, Victoria Múgica, Carolina Cisneros, Santiago Angulo‐Díaz‐Parreño, Coral Barbas, Carlos Blanco, Teresa Carrillo, Domingo Barber, Alma Villaseñor, María M. Escribese","doi":"10.1111/all.16434","DOIUrl":"https://doi.org/10.1111/all.16434","url":null,"abstract":"RationaleBiologics are becoming increasingly important in the management of severe asthma. However, little is known about the systemic immunometabolic consequences of Th2 response blockage.ObjectivesTo provide a better immunometabolic understanding of the effects of mepolizumab and omalizumab treatments by identifying potential biomarkers for monitoring.MethodsIn this exploratory longitudinal study severe asthmatic patients were followed for 18 months after initiating mepolizumab (<jats:italic>n</jats:italic> = 36) or Omalizumab (<jats:italic>n</jats:italic> = 20) treatment. Serum samples were collected before, 6, and 18 months after treatment. Targeted omic approaches were performed to analyze inflammatory metabolites (<jats:italic>n</jats:italic> = 35) and proteins (<jats:italic>n</jats:italic> = 45). Multiomic integration was performed individually for each treatment applying supervised analysis Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) framework. Then, potential biomarkers were confirmed using multivariate ROC analyses and correlated with clinical variables along treatment.Measurements and Main ResultsMepolizumab and omalizumab were both effective (improved clinical variables) and showed different and specific metabolic and protein profiles in severe asthmatic patients during treatment. Multiomic integration and multivariate ROC analyses identified specific biomarkers, such as arachidonic acid, palmitoleic acid, oleic acid, propionylcarnitine, bilirubin, CCL11, and TNFSF10, which can explain the differences observed with Mepolizumab treatment over 18 months and significantly correlate with clinical improvement. However, no significant biomolecules and no discriminative multivariate ROC curves were found for Omalizumab treatment.ConclusionsOur results provide a comprehensive insight into the differential effects of mepolizumab and omalizumab on the immunometabolic kinetics of the inflammatory response in severe asthma. We identified a set of biomolecules with potential for monitoring mepolizumab treatment which could be useful for personalized medicine.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"54 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841020","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}
Marek Jutel, Magdalena Zemelka-Wiacek, Yoshitaka Okamoto, Oliver Pfaar
{"title":"Algorithms in Allergy: Assessment of Rhinitis Using Allergen Exposure Chambers.","authors":"Marek Jutel, Magdalena Zemelka-Wiacek, Yoshitaka Okamoto, Oliver Pfaar","doi":"10.1111/all.16444","DOIUrl":"https://doi.org/10.1111/all.16444","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833195","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}
I Agache, I M Adcock, C A Akdis, M Akdis, G Bentabol-Ramos, M van den Berge, C Boccabella, W G Canonica, C Caruso, M Couto, I Davila, D Drummond, J Fonseca, A Gherasim, S Del Giacco, D J Jackson, M Jutel, A Licari, S Loukides, A Moreira, M Mukherjee, I Ojanguren, O Palomares, A Papi, L Perez de Llano, O J Price, M Rukhazde, M H Shamji, D Shaw, S Sanchez-Garcia, A Testera-Montes, M J Torres, I Eguiluz-Gracia
As cholinergic innervation is a major contributor to increased vagal tone and mucus secretion, inhaled long-acting muscarinic antagonists (LAMA) are a pillar for the treatment of chronic obstructive pulmonary disease and asthma. By blocking the muscarinic receptors expressed in the lung, LAMA improve lung function and reduce exacerbations in asthma patients who remained poorly controlled despite treatment with inhaled corticosteroids and long-acting β2 agonists. Asthma guidelines recommend LAMA as a third controller to be added on before the initiation of biologicals. In addition to bronchodilation, LAMA also exert anti-inflammatory and anti-fibrotic effects by inhibiting muscarinic receptors present in neutrophils, macrophages, fibroblasts and airway smooth muscle cells. Thus, besides bronchodilation, LAMA might provide additional therapeutic effects, thereby supporting an endotype-driven approach to asthma management. The Position Paper, developed by the Asthma Section of the European Academy of Allergy and Clinical Immunology, discusses the main cholinergic pathways in the lung, reviews the findings of significant clinical trials and real-life studies on LAMA use in asthma, examines the placement of these drugs in asthma clinical guidelines, and considers the potential for personalised medicine with LAMA in both adult and paediatric asthma patients.
胆碱能神经支配是迷走神经张力和粘液分泌增加的主要原因，因此吸入长效毒蕈碱拮抗剂（LAMA）是治疗慢性阻塞性肺病和哮喘的支柱。通过阻断肺部表达的毒蕈碱受体，长效毒蕈碱拮抗剂可改善哮喘患者的肺功能并减少病情恶化，这些患者在使用吸入式皮质类固醇和长效β2受体激动剂治疗后病情仍未得到有效控制。哮喘指南建议在开始使用生物制剂之前，将 LAMA 作为第三种控制药物。除支气管扩张作用外，LAMA 还能抑制中性粒细胞、巨噬细胞、成纤维细胞和气道平滑肌细胞中的毒蕈碱受体，从而发挥抗炎和抗纤维化作用。因此，除了支气管扩张作用外，LAMA 还可能提供其他治疗效果，从而支持以内型为导向的哮喘治疗方法。这份由欧洲过敏与临床免疫学会哮喘分会编写的立场文件讨论了肺部的主要胆碱能通路，回顾了有关 LAMA 用于哮喘的重要临床试验和实际生活研究的结果，研究了这些药物在哮喘临床指南中的位置，并考虑了在成人和儿童哮喘患者中使用 LAMA 进行个性化治疗的潜力。
{"title":"The Bronchodilator and Anti-Inflammatory Effect of Long-Acting Muscarinic Antagonists in Asthma: An EAACI Position Paper.","authors":"I Agache, I M Adcock, C A Akdis, M Akdis, G Bentabol-Ramos, M van den Berge, C Boccabella, W G Canonica, C Caruso, M Couto, I Davila, D Drummond, J Fonseca, A Gherasim, S Del Giacco, D J Jackson, M Jutel, A Licari, S Loukides, A Moreira, M Mukherjee, I Ojanguren, O Palomares, A Papi, L Perez de Llano, O J Price, M Rukhazde, M H Shamji, D Shaw, S Sanchez-Garcia, A Testera-Montes, M J Torres, I Eguiluz-Gracia","doi":"10.1111/all.16436","DOIUrl":"https://doi.org/10.1111/all.16436","url":null,"abstract":"<p><p>As cholinergic innervation is a major contributor to increased vagal tone and mucus secretion, inhaled long-acting muscarinic antagonists (LAMA) are a pillar for the treatment of chronic obstructive pulmonary disease and asthma. By blocking the muscarinic receptors expressed in the lung, LAMA improve lung function and reduce exacerbations in asthma patients who remained poorly controlled despite treatment with inhaled corticosteroids and long-acting β2 agonists. Asthma guidelines recommend LAMA as a third controller to be added on before the initiation of biologicals. In addition to bronchodilation, LAMA also exert anti-inflammatory and anti-fibrotic effects by inhibiting muscarinic receptors present in neutrophils, macrophages, fibroblasts and airway smooth muscle cells. Thus, besides bronchodilation, LAMA might provide additional therapeutic effects, thereby supporting an endotype-driven approach to asthma management. The Position Paper, developed by the Asthma Section of the European Academy of Allergy and Clinical Immunology, discusses the main cholinergic pathways in the lung, reviews the findings of significant clinical trials and real-life studies on LAMA use in asthma, examines the placement of these drugs in asthma clinical guidelines, and considers the potential for personalised medicine with LAMA in both adult and paediatric asthma patients.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826815","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}
Wouter W. de Weger, Aline. B. Sprikkelman, Catherina. E. M. Herpertz, Gerbrich N. van der Meulen, Judith. M. Vonk, Gerard. H. Koppelman, Arvid. W. A. Kamps
BackgroundDouble‐blind placebo‐controlled food challenge (DBPCFC) is widely regarded as the “gold standard” to diagnose food allergy. Maximum efforts are made to reduce bias, yet DBPCFCs are costly, time‐, and resource‐intensive. Less demanding open food challenges are increasingly used in clinical practice. However, recommendations regarding the use of these challenges are based on low certainty of evidence, and no comparative studies have been performed using the most recent international food challenge guidelines. We hypothesised that the open food challenge is non‐inferior to DBPCFC in children suspected of allergy to cashew nuts, hazelnuts or peanuts.MethodsA total of 63 children, aged 4 years and older, were included if referred for suspected IgE‐mediated allergy to cashew nut, hazelnut, or peanut. All study participants underwent DBPCFC first, followed by an open food challenge for the same food. Challenge outcomes were assessed by predefined criteria into positive, negative, or inconclusive.ResultsDBPCFC and open food challenge outcomes were the same for 36/41 (87.8%) patients. Sensitivity and specificity of the open food challenge were 0.91 (95% CI 0.79, 1.03) and 0.83 (95% CI 0.63, 1.01), respectively, with an AUC value of 0.87. Eliciting and stop doses were not significantly different between both food challenges.ConclusionThe Diagnostic accuracy of open food challenge is non‐inferior to that of DBPCFC. This finding implies less demanding open food challenges can be implemented for children from the age of 4 years suspected to be cashew nut, hazelnut, or peanut allergic. Further research is necessary to validate our findings and to investigate the diagnostic accuracy for other major food allergens.
{"title":"Comparison of Double‐Blind and Open Food Challenges for the Diagnosis of Food Allergy in Childhood: The ALDORADO Study","authors":"Wouter W. de Weger, Aline. B. Sprikkelman, Catherina. E. M. Herpertz, Gerbrich N. van der Meulen, Judith. M. Vonk, Gerard. H. Koppelman, Arvid. W. A. Kamps","doi":"10.1111/all.16428","DOIUrl":"https://doi.org/10.1111/all.16428","url":null,"abstract":"BackgroundDouble‐blind placebo‐controlled food challenge (DBPCFC) is widely regarded as the “gold standard” to diagnose food allergy. Maximum efforts are made to reduce bias, yet DBPCFCs are costly, time‐, and resource‐intensive. Less demanding open food challenges are increasingly used in clinical practice. However, recommendations regarding the use of these challenges are based on low certainty of evidence, and no comparative studies have been performed using the most recent international food challenge guidelines. We hypothesised that the open food challenge is non‐inferior to DBPCFC in children suspected of allergy to cashew nuts, hazelnuts or peanuts.MethodsA total of 63 children, aged 4 years and older, were included if referred for suspected IgE‐mediated allergy to cashew nut, hazelnut, or peanut. All study participants underwent DBPCFC first, followed by an open food challenge for the same food. Challenge outcomes were assessed by predefined criteria into positive, negative, or inconclusive.ResultsDBPCFC and open food challenge outcomes were the same for 36/41 (87.8%) patients. Sensitivity and specificity of the open food challenge were 0.91 (95% CI 0.79, 1.03) and 0.83 (95% CI 0.63, 1.01), respectively, with an AUC value of 0.87. Eliciting and stop doses were not significantly different between both food challenges.ConclusionThe Diagnostic accuracy of open food challenge is non‐inferior to that of DBPCFC. This finding implies less demanding open food challenges can be implemented for children from the age of 4 years suspected to be cashew nut, hazelnut, or peanut allergic. Further research is necessary to validate our findings and to investigate the diagnostic accuracy for other major food allergens.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"16 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820673","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}
Marianne Baastrup Soendergaard, Susanne Hansen, Kjell Erik Julius Håkansson, Anna von Bülow, Anne‐Sofie Bjerrum, Johannes Martin Schmid, Sofie Lock Johansson, Linda Makowska Rasmussen, Claus Rikard Johnsen, Barbara Bonnesen Bertelsen, Niels Steen Krogh, Ole Hilberg, Charlotte Suppli Ulrik, Celeste Porsbjerg
BackgroundIn patients with severe asthma, treatment with anti‐interleukin‐5 (IL‐5) biologics can lead to a reduction in fractional exhaled nitric oxide (FeNO) in some patients. The clinical implications of varying FeNO responses to anti‐IL‐5 biologics remain unclear. This study aims to categorise patients based on their FeNO response to anti‐IL‐5 biologics and evaluate the association of these categories with clinical outcomes.MethodsWe used the Danish Severe Asthma Register (DSAR) to identify the early FeNO response profiles in patients receiving anti‐IL5 biologics. We defined FeNO responders as patients with elevated FeNO levels at baseline and a decrease corresponding to the minimal clinically important difference (MCID) at 4 months of follow‐up and FeNO non‐responders as those who did not experience a decrease.ResultsWe identified 403 patients on anti‐IL5 treatment in DSAR, and 265 (66%) had elevated FeNO levels at baseline. After 4 months of treatment, 151 (57%) patients showed a significant decrease in FeNO levels, and 114 (43%) did not. FeNO responders were more likely to achieve clinical remission of asthma (34% vs. 19%, p = 0.01, OR 2.11, CI 1.04, 5.18, p = 0.03) than FeNO non‐responders after 12 months of treatment. The higher remission rates in FeNO responders mainly reflected a higher rate of normalisation of lung function.ConclusionsFeNO levels were reduced after anti‐IL5 treatment in a significant proportion of patients treated with anti‐IL5, and this was associated with clinical remission. Early FeNO response to anti‐IL5 could potentially be used as a biomarker to guide management decisions with biologics towards remission of disease in severe asthma.
{"title":"Early Reduction of FeNO on Anti‐IL5 Biologics Is Associated With Clinical Remission of Severe Asthma","authors":"Marianne Baastrup Soendergaard, Susanne Hansen, Kjell Erik Julius Håkansson, Anna von Bülow, Anne‐Sofie Bjerrum, Johannes Martin Schmid, Sofie Lock Johansson, Linda Makowska Rasmussen, Claus Rikard Johnsen, Barbara Bonnesen Bertelsen, Niels Steen Krogh, Ole Hilberg, Charlotte Suppli Ulrik, Celeste Porsbjerg","doi":"10.1111/all.16425","DOIUrl":"https://doi.org/10.1111/all.16425","url":null,"abstract":"BackgroundIn patients with severe asthma, treatment with anti‐interleukin‐5 (IL‐5) biologics can lead to a reduction in fractional exhaled nitric oxide (FeNO) in some patients. The clinical implications of varying FeNO responses to anti‐IL‐5 biologics remain unclear. This study aims to categorise patients based on their FeNO response to anti‐IL‐5 biologics and evaluate the association of these categories with clinical outcomes.MethodsWe used the Danish Severe Asthma Register (DSAR) to identify the early FeNO response profiles in patients receiving anti‐IL5 biologics. We defined FeNO responders as patients with elevated FeNO levels at baseline and a decrease corresponding to the minimal clinically important difference (MCID) at 4 months of follow‐up and FeNO non‐responders as those who did not experience a decrease.ResultsWe identified 403 patients on anti‐IL5 treatment in DSAR, and 265 (66%) had elevated FeNO levels at baseline. After 4 months of treatment, 151 (57%) patients showed a significant decrease in FeNO levels, and 114 (43%) did not. FeNO responders were more likely to achieve clinical remission of asthma (34% vs. 19%, <jats:italic>p</jats:italic> = 0.01, OR 2.11, CI 1.04, 5.18, <jats:italic>p</jats:italic> = 0.03) than FeNO non‐responders after 12 months of treatment. The higher remission rates in FeNO responders mainly reflected a higher rate of normalisation of lung function.ConclusionsFeNO levels were reduced after anti‐IL5 treatment in a significant proportion of patients treated with anti‐IL5, and this was associated with clinical remission. Early FeNO response to anti‐IL5 could potentially be used as a biomarker to guide management decisions with biologics towards remission of disease in severe asthma.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"14 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820674","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}
Coco Dekkers, Nicolaas Zuithoff, Daphne Bakker, Edward Knol, Anne Wevers, Wouter Touwslager, Wianda Christoffers, Petra Prosje, Anneke van Lynden‐van Nes, Paula van Lümig, Marijke Kamsteeg, Albert Jan Oosting, Marie L. A. Schuttelaar, Inge Haeck, Marlies de Graaf, Femke van Wijk, Marjolein de Bruin‐Weller
Introduction and ObjectivesTralokinumab—a biological that specifically targets interleukin‐13—is one of the newer advanced systemic treatments for patients with moderate‐to‐severe atopic dermatitis (AD). Although safety and efficacy have been shown in phase‐III clinical trials, daily practice data are needed. Therefore, the aim of this study was to evaluate 28‐week safety and effectiveness, serum proteins and total IgE levels in adult AD patients treated with tralokinumab in daily practice.Materials and MethodsData of all adult AD patients who started treatment with tralokinumab and participated in the BioDay registry were collected at baseline, and after 4,16 and 28 weeks of treatment. Clinical efficacy was evaluated by clinical outcome measures, such as the Eczema Area and Severity Index (EASI) as well as patient‐reported outcome measures, such as the numerical rating scale (NRS) for pruritus. Adverse events were evaluated. In a subgroup of patients, 18 proteins as well as total IgE levels were measured in serum.ResultsA total of 84 patients were included, of whom 39 were dupilumab‐naïve (D‐naïve) and 45 were dupilumab non‐naïve (D‐non‐naïve) patients. All primary outcomes significantly improved during 28 weeks of tralokinumab treatment and the probability of achieving EASI ≤ 7 and NRS‐pruritis ≤ 4 was 75.8% (56.9–88.2) and 51.4% (28.0–74.2), respectively. The disease severity‐associated proteins TARC/CCL17 and PARC/CCL18 decreased during treatment, and total IgE levels significantly decreased in the D‐naïve patients. The most reported adverse events were eye disorders (n = 24, 28.6%). A total of 23 patients (27.4%) discontinued treatment due to adverse events and/or ineffectiveness, with hair loss being the most common adverse event leading to treatment discontinuation (n = 6).ConclusionTralokinumab is an effective treatment for moderate‐to‐severe AD in adult patients, in both dupilumab‐naïve patients and patients who previously failed on dupilumab treatment. The clinical effect is supported by the biological data.
{"title":"Tralokinumab Treatment in Adult Atopic Dermatitis Patients: 28‐Week Evaluation of Clinical Effectiveness, Safety, Serum Proteins and Total IgE Levels","authors":"Coco Dekkers, Nicolaas Zuithoff, Daphne Bakker, Edward Knol, Anne Wevers, Wouter Touwslager, Wianda Christoffers, Petra Prosje, Anneke van Lynden‐van Nes, Paula van Lümig, Marijke Kamsteeg, Albert Jan Oosting, Marie L. A. Schuttelaar, Inge Haeck, Marlies de Graaf, Femke van Wijk, Marjolein de Bruin‐Weller","doi":"10.1111/all.16414","DOIUrl":"https://doi.org/10.1111/all.16414","url":null,"abstract":"Introduction and ObjectivesTralokinumab—a biological that specifically targets interleukin‐13—is one of the newer advanced systemic treatments for patients with moderate‐to‐severe atopic dermatitis (AD). Although safety and efficacy have been shown in phase‐III clinical trials, daily practice data are needed. Therefore, the aim of this study was to evaluate 28‐week safety and effectiveness, serum proteins and total IgE levels in adult AD patients treated with tralokinumab in daily practice.Materials and MethodsData of all adult AD patients who started treatment with tralokinumab and participated in the BioDay registry were collected at baseline, and after 4,16 and 28 weeks of treatment. Clinical efficacy was evaluated by clinical outcome measures, such as the Eczema Area and Severity Index (EASI) as well as patient‐reported outcome measures, such as the numerical rating scale (NRS) for pruritus. Adverse events were evaluated. In a subgroup of patients, 18 proteins as well as total IgE levels were measured in serum.ResultsA total of 84 patients were included, of whom 39 were dupilumab‐naïve (D‐naïve) and 45 were dupilumab non‐naïve (D‐non‐naïve) patients. All primary outcomes significantly improved during 28 weeks of tralokinumab treatment and the probability of achieving EASI ≤ 7 and NRS‐pruritis ≤ 4 was 75.8% (56.9–88.2) and 51.4% (28.0–74.2), respectively. The disease severity‐associated proteins TARC/CCL17 and PARC/CCL18 decreased during treatment, and total IgE levels significantly decreased in the D‐naïve patients. The most reported adverse events were eye disorders (<jats:italic>n</jats:italic> = 24, 28.6%). A total of 23 patients (27.4%) discontinued treatment due to adverse events and/or ineffectiveness, with hair loss being the most common adverse event leading to treatment discontinuation (<jats:italic>n</jats:italic> = 6).ConclusionTralokinumab is an effective treatment for moderate‐to‐severe AD in adult patients, in both dupilumab‐naïve patients and patients who previously failed on dupilumab treatment. The clinical effect is supported by the biological data.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"47 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820762","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}
Sayantani B. Sindher, Kari C. Nadeau, R. Sharon Chinthrajah, Jeffrey G. Leflein, Philippe Bégin, Jason A. Ohayon, Punita Ponda, Erik Wambre, Jinzhong Liu, Faisal A. Khokhar, Bolanle Akinlade, Jennifer Maloney, Jamie M. Orengo, Jennifer D. Hamilton, Mohamed A. Kamal, Andrea T. Hooper, Naimish Patel, Kiran Patel, Elizabeth Laws, Leda P. Mannent, Allen R. Radin
BackgroundPeanut allergy is a potentially life‐threatening food allergy in children. This study explored whether dupilumab, a human monoclonal immunoglobulin (Ig)G4 antibody that blocks the activity of interleukin (IL)‐4/IL‐13, improved safety and desensitization to peanut exposure in children with peanut allergy.MethodsA Phase II, 24‐week, multicenter, single‐arm, open‐label, proof‐of‐concept study was conducted in the USA and Canada (NCT03793608). Children/adolescents with peanut allergy received subcutaneous dupilumab 300 mg (≥ 60 kg) or 200 mg (≥ 20 to < 60 kg) every 2 weeks. The primary endpoint was the proportion of participants who passed a double‐blind placebo‐controlled food challenge (DBPCFC) with ≥ 444 mg (cumulative) of peanut protein at week 24. Secondary endpoints included safety measures (Consortium of Food Allergy Research grading system) and change from baseline in peanut‐specific (ps)‐IgG4, total IgE, and ps‐IgE.ResultsTwenty‐four participants enrolled and received dupilumab: 75.0% were male, 79.2% were white, mean (standard deviation) age was 11.7 (3.3) years. Most (95.8%) participants had not received allergen immunotherapy. Two participants (8.3%) achieved the primary endpoint and passed the DBPCFC at week 24. Fifteen participants (62.5%) reported 66 treatment‐emergent adverse events, all being mild or in moderate intensity. At the week 24 DBPCFC, 8 participants (33.3%) had a grade 2 allergic reaction (no grade 3 or above); 10 (41.7%) used adrenaline as a rescue medication. Dupilumab treatment resulted in a median reduction of total and ps‐IgE of −54% and −49%, respectively, and a 0% change in ps‐IgG4.ConclusionsDupilumab monotherapy treatment for 24 weeks did not improve desensitization to peanut exposure after food challenge.
{"title":"Efficacy and Safety of Dupilumab in Children With Peanut Allergy: A Multicenter, Open‐Label, Phase II Study","authors":"Sayantani B. Sindher, Kari C. Nadeau, R. Sharon Chinthrajah, Jeffrey G. Leflein, Philippe Bégin, Jason A. Ohayon, Punita Ponda, Erik Wambre, Jinzhong Liu, Faisal A. Khokhar, Bolanle Akinlade, Jennifer Maloney, Jamie M. Orengo, Jennifer D. Hamilton, Mohamed A. Kamal, Andrea T. Hooper, Naimish Patel, Kiran Patel, Elizabeth Laws, Leda P. Mannent, Allen R. Radin","doi":"10.1111/all.16404","DOIUrl":"https://doi.org/10.1111/all.16404","url":null,"abstract":"BackgroundPeanut allergy is a potentially life‐threatening food allergy in children. This study explored whether dupilumab, a human monoclonal immunoglobulin (Ig)G4 antibody that blocks the activity of interleukin (IL)‐4/IL‐13, improved safety and desensitization to peanut exposure in children with peanut allergy.MethodsA Phase II, 24‐week, multicenter, single‐arm, open‐label, proof‐of‐concept study was conducted in the USA and Canada (NCT03793608). Children/adolescents with peanut allergy received subcutaneous dupilumab 300 mg (≥ 60 kg) or 200 mg (≥ 20 to < 60 kg) every 2 weeks. The primary endpoint was the proportion of participants who passed a double‐blind placebo‐controlled food challenge (DBPCFC) with ≥ 444 mg (cumulative) of peanut protein at week 24. Secondary endpoints included safety measures (Consortium of Food Allergy Research grading system) and change from baseline in peanut‐specific (ps)‐IgG4, total IgE, and ps‐IgE.ResultsTwenty‐four participants enrolled and received dupilumab: 75.0% were male, 79.2% were white, mean (standard deviation) age was 11.7 (3.3) years. Most (95.8%) participants had not received allergen immunotherapy. Two participants (8.3%) achieved the primary endpoint and passed the DBPCFC at week 24. Fifteen participants (62.5%) reported 66 treatment‐emergent adverse events, all being mild or in moderate intensity. At the week 24 DBPCFC, 8 participants (33.3%) had a grade 2 allergic reaction (no grade 3 or above); 10 (41.7%) used adrenaline as a rescue medication. Dupilumab treatment resulted in a median reduction of total and ps‐IgE of −54% and −49%, respectively, and a 0% change in ps‐IgG4.ConclusionsDupilumab monotherapy treatment for 24 weeks did not improve desensitization to peanut exposure after food challenge.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"100 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820676","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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