Pub Date : 2025-02-15DOI: 10.1016/j.jacig.2025.100440
Raymond Mak MD , Edmond S. Chan MD , Michael Irvine PhD , Jia Yi Huang MSC , James Hethey MD , Sheila Hartstein MD , Li Wang MD
Background
Peanut component–resolved diagnostics (peanut CRD) is a potentially valuable tool for distinguishing between anaphylactic peanut allergies and milder phenotypes, such as pollen–food allergy syndrome. However, the optimal strategy for integrating CRD into clinical practice remains unclear.
Objective
This study aims to evaluate the rates of oral food challenge (OFC) when CRD is ordered: routinely for all patients, selectively on the basis of clinical characteristics, or guided by other peanut biomarkers.
Methods
We compared OFC rates between 2 cohorts. Cohort 1 included patients with peanut allergy who received CRD as part of routine testing, regardless of clinical features. In cohort 2, CRD was ordered selectively, depending on factors such as older age, comorbidities, or pollen sensitization. OFC was offered at the physician's discretion in both cohorts. Later, a proposed 2-step clinical algorithm was retrospectively applied to the pooled data to determine patients eligible for OFC.
Results
A total of 322 patients (137 in cohort 1 and 185 in cohort 2) participated in the study. OFC rates were lower in the selective testing group (9.7%) and with use of an algorithm (9.5%) than in the group that underwent routine testing (25.5%). The correlation between peanut-specific IgE level and CRD result was high (R = 0.85).
Conclusion
Offering CRD selectively on the basis of clinical characteristics and being guided by a 2-step algorithm are more efficient strategies that can reduce rates of OFC to enhance patient safety, optimize health care resource utilization, and reduce costs. As peanut-specific IgE level and CRD result correlate well, testing for Ara h 2 is likely redundant at very high and low ranges.
{"title":"Comparing approaches to ordering peanut component–resolved diagnostics to reduce the need for oral food challenges","authors":"Raymond Mak MD , Edmond S. Chan MD , Michael Irvine PhD , Jia Yi Huang MSC , James Hethey MD , Sheila Hartstein MD , Li Wang MD","doi":"10.1016/j.jacig.2025.100440","DOIUrl":"10.1016/j.jacig.2025.100440","url":null,"abstract":"<div><h3>Background</h3><div>Peanut component–resolved diagnostics (peanut CRD) is a potentially valuable tool for distinguishing between anaphylactic peanut allergies and milder phenotypes, such as pollen–food allergy syndrome. However, the optimal strategy for integrating CRD into clinical practice remains unclear.</div></div><div><h3>Objective</h3><div>This study aims to evaluate the rates of oral food challenge (OFC) when CRD is ordered: routinely for all patients, selectively on the basis of clinical characteristics, or guided by other peanut biomarkers.</div></div><div><h3>Methods</h3><div>We compared OFC rates between 2 cohorts. Cohort 1 included patients with peanut allergy who received CRD as part of routine testing, regardless of clinical features. In cohort 2, CRD was ordered selectively, depending on factors such as older age, comorbidities, or pollen sensitization. OFC was offered at the physician's discretion in both cohorts. Later, a proposed 2-step clinical algorithm was retrospectively applied to the pooled data to determine patients eligible for OFC.</div></div><div><h3>Results</h3><div>A total of 322 patients (137 in cohort 1 and 185 in cohort 2) participated in the study. OFC rates were lower in the selective testing group (9.7%) and with use of an algorithm (9.5%) than in the group that underwent routine testing (25.5%). The correlation between peanut-specific IgE level and CRD result was high (<em>R</em> = 0.85).</div></div><div><h3>Conclusion</h3><div>Offering CRD selectively on the basis of clinical characteristics and being guided by a 2-step algorithm are more efficient strategies that can reduce rates of OFC to enhance patient safety, optimize health care resource utilization, and reduce costs. As peanut-specific IgE level and CRD result correlate well, testing for Ara h 2 is likely redundant at very high and low ranges.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100440"},"PeriodicalIF":0.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with severe asthma may demonstrate reduced sensitivity to steroid treatment. However, the implications of this reduced responsiveness for clinical outcomes and the underlying mechanisms remain unclear.
Objective
The aim of this study was to investigate whether steroid sensitivity in patients with asthma is related to severity and clinical outcomes and to elucidate the role of inflammatory pathways in reducing steroid sensitivity.
Methods
This observational study of 169 asthma patients, with 161 followed for 1 year, involved isolation of peripheral blood mononuclear cells. These cells were treated with dexamethasone, and the mRNA expression of FKBP5, which is a marker of steroid sensitivity, was measured. To explore the mechanism underlying the reduced steroid sensitivity, cells were exposed to PI3K and MAPK inhibitors in combination with dexamethasone.
Results
A total of 53 patients diagnosed with severe asthma exhibited markedly diminished sensitivity to steroids compared with those with nonsevere asthma. Reduced steroid sensitivity has emerged as a critical risk factor for failure to experience clinical remission and exacerbation. This relationship between reduced steroid sensitivity and disease severity and adverse outcomes was confirmed at the 1-year follow-up. Mechanistic investigations revealed that the degree of recovery from steroid sensitivity after PI3Kδ/γ inhibitor treatment was significantly greater in patients with severe asthma than in those with nonsevere asthma, a finding confirmed at the 1-year follow-up.
Conclusions
Patients with severe asthma demonstrate reduced steroid sensitivity, which results in unfavorable clinical outcomes. Conversely, inhibition of the PI3K pathway significantly improves steroid sensitivity.
{"title":"PI3K pathway activation in severe asthma is linked to steroid insensitivity and adverse outcomes","authors":"Sekiko Uehara BSc , Keita Hirai PhD , Toshihiro Shirai MD, PhD , Taisuke Akamatsu MD, PhD , Kunihiko Itoh PhD","doi":"10.1016/j.jacig.2025.100439","DOIUrl":"10.1016/j.jacig.2025.100439","url":null,"abstract":"<div><h3>Background</h3><div>Patients with severe asthma may demonstrate reduced sensitivity to steroid treatment. However, the implications of this reduced responsiveness for clinical outcomes and the underlying mechanisms remain unclear.</div></div><div><h3>Objective</h3><div>The aim of this study was to investigate whether steroid sensitivity in patients with asthma is related to severity and clinical outcomes and to elucidate the role of inflammatory pathways in reducing steroid sensitivity.</div></div><div><h3>Methods</h3><div>This observational study of 169 asthma patients, with 161 followed for 1 year, involved isolation of peripheral blood mononuclear cells. These cells were treated with dexamethasone, and the mRNA expression of <em>FKBP5,</em> which is a marker of steroid sensitivity, was measured. To explore the mechanism underlying the reduced steroid sensitivity, cells were exposed to PI3K and MAPK inhibitors in combination with dexamethasone.</div></div><div><h3>Results</h3><div>A total of 53 patients diagnosed with severe asthma exhibited markedly diminished sensitivity to steroids compared with those with nonsevere asthma. Reduced steroid sensitivity has emerged as a critical risk factor for failure to experience clinical remission and exacerbation. This relationship between reduced steroid sensitivity and disease severity and adverse outcomes was confirmed at the 1-year follow-up. Mechanistic investigations revealed that the degree of recovery from steroid sensitivity after PI3Kδ/γ inhibitor treatment was significantly greater in patients with severe asthma than in those with nonsevere asthma, a finding confirmed at the 1-year follow-up.</div></div><div><h3>Conclusions</h3><div>Patients with severe asthma demonstrate reduced steroid sensitivity, which results in unfavorable clinical outcomes. Conversely, inhibition of the PI3K pathway significantly improves steroid sensitivity.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100439"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-05DOI: 10.1016/j.jacig.2025.100435
Mikyeong Lee PhD , Hilde Kristin Vindenes MD, PhD , Farnaz Fouladi PhD , Rajesh Shigdel PhD , James M. Ward MSc , Shayamal D. Peddada PhD , Stephanie J. London MD, DrPH , Randi Jacobsen Bertelsen PhD
Background
Oral microbiome composition has been linked to onset and progression of several localized and systemic diseases. Associations with allergy in adults have been less explored.
Objective
We sought to identify oral microbiota associated with allergy outcomes in adults using high-throughput sequencing data.
Methods
We characterized bacterial communities of gingival samples from 453 Norwegian adults (average age, 28 years) using 16S rRNA gene amplicon sequencing. We examined more than 2200 bacterial taxa in relation to self-reported current asthma, eczema, or rhinitis, and seroatopy (IgE > 0.70 kU/L). We used linear regression to determine whether overall bacterial diversity differed by each allergic outcome and analysis of composition of microbiomes with bias correction (ANCOM-BC2) to identify differentially abundant taxa.
Results
Less diverse oral bacterial communities were observed (P < .05) in individuals with atopy or rhinitis compared with those without. Bacterial diversity did not differ by asthma and eczema status. While no bacterial taxa were differentially abundant by asthma, many were differentially abundant (P < .05 after multiple-testing correction) in relation to atopy, eczema, and rhinitis. These taxa include several from the genera Leptotrichia and Fusobacterium. Some, including Streptococcus, were previously implicated in respiratory health, whereas others were novel. We also found taxa related to nasal medication use in individuals with rhinitis. Notably, microbial network interconnections differed by allergy status.
Conclusions
Bacterial community compositions of oral gingival samples may play a role in allergic outcomes in adults. These findings could contribute to the development of novel treatment strategies.
{"title":"Oral microbiota related to allergy in Norwegian adults","authors":"Mikyeong Lee PhD , Hilde Kristin Vindenes MD, PhD , Farnaz Fouladi PhD , Rajesh Shigdel PhD , James M. Ward MSc , Shayamal D. Peddada PhD , Stephanie J. London MD, DrPH , Randi Jacobsen Bertelsen PhD","doi":"10.1016/j.jacig.2025.100435","DOIUrl":"10.1016/j.jacig.2025.100435","url":null,"abstract":"<div><h3>Background</h3><div>Oral microbiome composition has been linked to onset and progression of several localized and systemic diseases. Associations with allergy in adults have been less explored.</div></div><div><h3>Objective</h3><div>We sought to identify oral microbiota associated with allergy outcomes in adults using high-throughput sequencing data.</div></div><div><h3>Methods</h3><div>We characterized bacterial communities of gingival samples from 453 Norwegian adults (average age, 28 years) using 16S rRNA gene amplicon sequencing. We examined more than 2200 bacterial taxa in relation to self-reported current asthma, eczema, or rhinitis, and seroatopy (IgE > 0.70 kU/L). We used linear regression to determine whether overall bacterial diversity differed by each allergic outcome and analysis of composition of microbiomes with bias correction (ANCOM-BC2) to identify differentially abundant taxa.</div></div><div><h3>Results</h3><div>Less diverse oral bacterial communities were observed (<em>P</em> < .05) in individuals with atopy or rhinitis compared with those without. Bacterial diversity did not differ by asthma and eczema status. While no bacterial taxa were differentially abundant by asthma, many were differentially abundant (<em>P</em> < .05 after multiple-testing correction) in relation to atopy, eczema, and rhinitis. These taxa include several from the genera <em>Leptotrichia and Fusobacterium</em>. Some, including <em>Streptococcus</em>, were previously implicated in respiratory health, whereas others were novel. We also found taxa related to nasal medication use in individuals with rhinitis. Notably, microbial network interconnections differed by allergy status.</div></div><div><h3>Conclusions</h3><div>Bacterial community compositions of oral gingival samples may play a role in allergic outcomes in adults. These findings could contribute to the development of novel treatment strategies.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100435"},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-04DOI: 10.1016/j.jacig.2025.100437
Michael E. Wechsler MD , Anna Kovalszki MD , Jared Silver MD, PhD , Brian Stone MD , William McCann MD , Lynn Huynh MPH, DrPH , Anamika Khanal BA , Mingchen Ye MS , Mei Sheng Duh MPH, ScD , Arijita Deb PhD
Background
Data on the presentation and management of patients with eosinophilic granulomatosis with polyangiitis (EGPA) in private practice are limited.
Objective
We sought to characterize the profiles and disease burden of patients with EGPA in a real-world private practice setting.
Methods
This was a retrospective, noninterventional, longitudinal study (GSK ID: 217426) of US Allergy Partners network data. For patients with a diagnosis of EGPA, confirmed by 2 or more EGPA clinical features, index was defined as their first visit with an Allergy Partners physician (January 2007–June 2021); postindex lasted until loss of follow-up or study end (December 2021). Patient characteristics at index, physician characteristics at any time, symptoms, treatment characteristics, and clinical outcomes postindex were assessed.
Results
Of 52 patients (median follow-up, 3.7 years), 75% were diagnosed with EGPA outside the Allergy Partners network. Each patient received care from a median (Q1-Q3) of 4.0 (3.0-5.0) physician specialties. Most had asthma (92%), rhinitis (75%), and sinusitis (62%) and experienced a mean ± SD of 18.1 ± 4.3 distinct self-reported symptoms. Most (85%) used oral corticosteroids, with 73% (32 of 44) on daily doses of more than 12 mg; 60% used mepolizumab. Overall, 75% of patients (39 of 52) achieved a response (improved/controlled symptoms); 46% (24 of 52) achieved controlled status after worsened, unchanged, or active symptoms, and of these 38% (9 of 24) relapsed.
Conclusions
The complex private practice presentation of EGPA, with heterogeneous patient response to standard treatments, highlights a significant disease burden and continued need for optimized treatment strategies within a multidisciplinary team approach.
{"title":"Eosinophilic granulomatosis with polyangiitis: Patient profiles from a large US allergy practice","authors":"Michael E. Wechsler MD , Anna Kovalszki MD , Jared Silver MD, PhD , Brian Stone MD , William McCann MD , Lynn Huynh MPH, DrPH , Anamika Khanal BA , Mingchen Ye MS , Mei Sheng Duh MPH, ScD , Arijita Deb PhD","doi":"10.1016/j.jacig.2025.100437","DOIUrl":"10.1016/j.jacig.2025.100437","url":null,"abstract":"<div><h3>Background</h3><div>Data on the presentation and management of patients with eosinophilic granulomatosis with polyangiitis (EGPA) in private practice are limited.</div></div><div><h3>Objective</h3><div>We sought to characterize the profiles and disease burden of patients with EGPA in a real-world private practice setting.</div></div><div><h3>Methods</h3><div>This was a retrospective, noninterventional, longitudinal study (GSK ID: 217426) of US Allergy Partners network data. For patients with a diagnosis of EGPA, confirmed by 2 or more EGPA clinical features, index was defined as their first visit with an Allergy Partners physician (January 2007–June 2021); postindex lasted until loss of follow-up or study end (December 2021). Patient characteristics at index, physician characteristics at any time, symptoms, treatment characteristics, and clinical outcomes postindex were assessed.</div></div><div><h3>Results</h3><div>Of 52 patients (median follow-up, 3.7 years), 75% were diagnosed with EGPA outside the Allergy Partners network. Each patient received care from a median (Q1-Q3) of 4.0 (3.0-5.0) physician specialties. Most had asthma (92%), rhinitis (75%), and sinusitis (62%) and experienced a mean ± SD of 18.1 ± 4.3 distinct self-reported symptoms. Most (85%) used oral corticosteroids, with 73% (32 of 44) on daily doses of more than 12 mg; 60% used mepolizumab. Overall, 75% of patients (39 of 52) achieved a response (improved/controlled symptoms); 46% (24 of 52) achieved controlled status after worsened, unchanged, or active symptoms, and of these 38% (9 of 24) relapsed.</div></div><div><h3>Conclusions</h3><div>The complex private practice presentation of EGPA, with heterogeneous patient response to standard treatments, highlights a significant disease burden and continued need for optimized treatment strategies within a multidisciplinary team approach.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100437"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A study demonstrated that drug provocation tests could be conducted in children with underlying diseases, enabling accurate diagnosis of drug allergy. The study investigators hope that their work will allow more children with underlying conditions to undergo drug provocation tests.
{"title":"Outcomes of drug provocation tests in children with chronic complications and comorbidities: Case series","authors":"Kouhei Hagino MD , Kiwako Yamamoto-Hanada MD, PhD , Seiko Hirai MD , Daisuke Harama MD, PhD , Marei Omori MD , Yasuaki Matsumoto MD , Daichi Suzuki MD , Kotaro Umezawa MD , Fumi Ishikawa MD , Kenji Toyokuni MD, PhD , Tatsuki Fukuie MD, PhD , Yukihiro Ohya MD, PhD","doi":"10.1016/j.jacig.2025.100436","DOIUrl":"10.1016/j.jacig.2025.100436","url":null,"abstract":"<div><div>A study demonstrated that drug provocation tests could be conducted in children with underlying diseases, enabling accurate diagnosis of drug allergy. The study investigators hope that their work will allow more children with underlying conditions to undergo drug provocation tests.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100436"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/S2772-8293(25)00025-6
{"title":"Aims and scope","authors":"","doi":"10.1016/S2772-8293(25)00025-6","DOIUrl":"10.1016/S2772-8293(25)00025-6","url":null,"abstract":"","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 1","pages":"Article 100424"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The incidence of food allergy (FA) has been increasing worldwide, causing growing concern on a global scale.
Objective
This birth cohort study analyzes the incidence of reported FA and other atopic comorbidities in children from birth to age 2 years who were living in 4 urban and semiurban areas in Iran.
Methods
Children were followed from birth until age 24 months, with follow-up questionnaires administered through parent or guardian interviews conducted when the children were aged 2, 4, 6, 12, and 24 months.
Results
The rate of physician-diagnosed FA reported by parents or guardians was higher than expected, with a cumulative incidence of 7.7% in children younger than 24 months. The highest prevalence of FA was found in Yazd, the most urban of the 4 cities studied. Breast-feeding was associated with a decreased cumulative risk of FA at age 12 months, with only 5% of breast-fed children developing parent-reported pediatrician-diagnosed FA compared with 13% of infants who never received breast milk after birth.
Conclusion
This study provides valuable insight into the incidence of FA in the Middle East, which has previously not been reported on, and it is crucial in our understanding of global FA prevalence. The study demonstrates a high incidence of FA in an area with historically lower rates and confirms that breast-feeding does prevent FA during infancy in this population.
{"title":"Prevalence of food allergy and its association with atopic dermatitis in Iran: Results from the PERSIAN birth cohort","authors":"Kylie Jungles MD , Maryam Sharafkhah MSc , Keerthi Bansal MD , Marjan Moallemian Isfahani MSc , Nashmia Qamar MD , Sareh Eghtesad PhD , Roya Kelishadi MD , Navid Danaei MD , Amir Houshang Mehrparvar MD , Hamid Hakimi MD , Hossein Poustchi MD, PhD , Mahboobeh Mahdavinia MD, PhD","doi":"10.1016/j.jacig.2024.100385","DOIUrl":"10.1016/j.jacig.2024.100385","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of food allergy (FA) has been increasing worldwide, causing growing concern on a global scale.</div></div><div><h3>Objective</h3><div>This birth cohort study analyzes the incidence of reported FA and other atopic comorbidities in children from birth to age 2 years who were living in 4 urban and semiurban areas in Iran.</div></div><div><h3>Methods</h3><div>Children were followed from birth until age 24 months, with follow-up questionnaires administered through parent or guardian interviews conducted when the children were aged 2, 4, 6, 12, and 24 months.</div></div><div><h3>Results</h3><div>The rate of physician-diagnosed FA reported by parents or guardians was higher than expected, with a cumulative incidence of 7.7% in children younger than 24 months. The highest prevalence of FA was found in Yazd, the most urban of the 4 cities studied. Breast-feeding was associated with a decreased cumulative risk of FA at age 12 months, with only 5% of breast-fed children developing parent-reported pediatrician-diagnosed FA compared with 13% of infants who never received breast milk after birth.</div></div><div><h3>Conclusion</h3><div>This study provides valuable insight into the incidence of FA in the Middle East, which has previously not been reported on, and it is crucial in our understanding of global FA prevalence. The study demonstrates a high incidence of FA in an area with historically lower rates and confirms that breast-feeding does prevent FA during infancy in this population.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 1","pages":"Article 100385"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jacig.2024.100383
Giorgio Walter Canonica MD , Gherardo Mazziotti MD, PhD , Alessandro Repici MD , Massimiliano Povero PhD , Luca Castello MSc , Lorenzo Pradelli MD , Miryana Dobreva MSc , Francesca Fanelli MSc , Jean Pierre Saab MD , Edoardo Vincenzo Savarino MD, PhD
Background
Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder marked by eosinophilic infiltration of the esophageal mucosa. Despite advances in understanding and management, optimal therapeutic strategies remain unclear, with conflicting guidelines.
Objective
We sought to evaluate effectiveness and safety of topical corticosteroids (TCSs) and proton pump inhibitors (PPIs) in managing EoE and their economic implications in Italy.
Methods
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched up to December 2023 and 78 publications were included, covering treatment outcomes and adverse events. Meta-analyses were performed to evaluate treatment efficacy and safety across various patient populations and study designs.
Results
TCSs showed superior efficacy over PPIs in achieving histologic, endoscopic, and partial clinical responses. Older patients responded better to both treatments. Treatment outcomes varied by sex and presence of atopic conditions. TCSs discontinuation increased the risk of clinical relapse (0.70 cases per person-year), whereas continuous use was linked to a rise in nonserious adverse events (dilation, infections, upper respiratory tract infections, and skin disorders). Economic analysis indicated cost variations based on treatment regimens and follow-up protocols, with dilation and relapse being significant cost drivers in Italy.
Conclusions
This review provides insights into efficacy, safety, and economic impact of TCSs and PPIs in managing EoE. TCSs were more effective in achieving histologic and endoscopic responses, whereas PPIs were effective in reducing symptoms. Standardized treatment guidelines are needed because of varied treatment efficacy across studies. Future research and new therapies may enhance outcomes and reduce health care costs, improving patient quality of life.
{"title":"The clinical impact of conventional therapies for adults and adolescents suffering from eosinophilic esophagitis, a type 2 inflammatory chronic disease, and their economic consequences in Italy: Systematic literature review and meta-analysis","authors":"Giorgio Walter Canonica MD , Gherardo Mazziotti MD, PhD , Alessandro Repici MD , Massimiliano Povero PhD , Luca Castello MSc , Lorenzo Pradelli MD , Miryana Dobreva MSc , Francesca Fanelli MSc , Jean Pierre Saab MD , Edoardo Vincenzo Savarino MD, PhD","doi":"10.1016/j.jacig.2024.100383","DOIUrl":"10.1016/j.jacig.2024.100383","url":null,"abstract":"<div><h3>Background</h3><div>Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder marked by eosinophilic infiltration of the esophageal mucosa. Despite advances in understanding and management, optimal therapeutic strategies remain unclear, with conflicting guidelines.</div></div><div><h3>Objective</h3><div>We sought to evaluate effectiveness and safety of topical corticosteroids (TCSs) and proton pump inhibitors (PPIs) in managing EoE and their economic implications in Italy.</div></div><div><h3>Methods</h3><div>MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched up to December 2023 and 78 publications were included, covering treatment outcomes and adverse events. Meta-analyses were performed to evaluate treatment efficacy and safety across various patient populations and study designs.</div></div><div><h3>Results</h3><div>TCSs showed superior efficacy over PPIs in achieving histologic, endoscopic, and partial clinical responses. Older patients responded better to both treatments. Treatment outcomes varied by sex and presence of atopic conditions. TCSs discontinuation increased the risk of clinical relapse (0.70 cases per person-year), whereas continuous use was linked to a rise in nonserious adverse events (dilation, infections, upper respiratory tract infections, and skin disorders). Economic analysis indicated cost variations based on treatment regimens and follow-up protocols, with dilation and relapse being significant cost drivers in Italy.</div></div><div><h3>Conclusions</h3><div>This review provides insights into efficacy, safety, and economic impact of TCSs and PPIs in managing EoE. TCSs were more effective in achieving histologic and endoscopic responses, whereas PPIs were effective in reducing symptoms. Standardized treatment guidelines are needed because of varied treatment efficacy across studies. Future research and new therapies may enhance outcomes and reduce health care costs, improving patient quality of life.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 1","pages":"Article 100383"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jacig.2024.100382
Edwin H. Kim MD, MS , Warner W. Carr MD , Amal H. Assa’ad MD , Shaila U. Gogate MD , Daniel H. Petroni MD, PhD , Thomas B. Casale MD , Mei-Lun Wang MD , Amy Sullivan BA , Amy M. Archer MD, PhD , Ouhong Wang PhD , Cheri Piscia-Nichols BS , Lisa Tuomi PharmD , Olga Levin-Young MBA , Ashley Dombkowski PhD , Dana McClintock MD , Harmony investigators
Background
Oral immunotherapy is an established approach to desensitize the immune system in the context of allergic disease; however, the only currently approved product is for peanut allergy. ADP101 is a novel, pharmaceutical-grade, multifood oral immunotherapy in development to simultaneously treat single or multiple food allergies, containing allergenic proteins from 15 foods in equal parts by protein weight.
Objective
The phase 1/2 Harmony trial (NCT04856865) evaluated efficacy and safety of ADP101 in participants with qualifying allergy to 1 to 5 foods in ADP101, defined as dose-limiting symptoms with a ≤100 mg challenge dose during double-blind, placebo-controlled food challenge (DBPCFC).
Methods
Participants were randomized to low-dose (1500 mg/d; 100 mg protein per food) or high-dose (4500 mg/d; 300 mg protein per food) ADP101, or matched placebo, with dose escalation followed by daily maintenance dosing over 40 weeks. The primary endpoint was the proportion of participants tolerating a ≥600 mg challenge dose of a single qualifying food without dose-limiting symptoms at the Week 40 Exit DBPCFC (ie, responders).
Results
In the primary analysis population (61 pediatric participants aged 4-17 years), a greater response rate was observed in both the high-dose ADP101 (55.0%) and low-dose ADP101 (38.1%) groups compared with pooled placebo (20.0%) (nominal P = .048, P = .306, respectively; adjusted for multiple comparisons, P = .097, P = .306, respectively). Desensitization to ≥2 foods was observed in individuals with multiple food allergies, as was desensitization at levels over 600 mg. ADP101-treated participants showed an overall reduction in skin-prick test reactivity, with an increase in maximum tolerated dose across the majority of foods tested. Adverse events were mostly mild or moderate, with no life-threatening events or deaths.
Conclusions
The study did not meet its primary endpoint, but ADP101 demonstrated a favorable safety profile and increased the reactive threshold in DBPCFC in pediatric participants with single or multiple food allergies across multiple endpoints, warranting further clinical investigation.
{"title":"ADP101 multifood oral immunotherapy for food-allergic patients: Harmony phase 1/2 randomized clinical trial","authors":"Edwin H. Kim MD, MS , Warner W. Carr MD , Amal H. Assa’ad MD , Shaila U. Gogate MD , Daniel H. Petroni MD, PhD , Thomas B. Casale MD , Mei-Lun Wang MD , Amy Sullivan BA , Amy M. Archer MD, PhD , Ouhong Wang PhD , Cheri Piscia-Nichols BS , Lisa Tuomi PharmD , Olga Levin-Young MBA , Ashley Dombkowski PhD , Dana McClintock MD , Harmony investigators","doi":"10.1016/j.jacig.2024.100382","DOIUrl":"10.1016/j.jacig.2024.100382","url":null,"abstract":"<div><h3>Background</h3><div>Oral immunotherapy is an established approach to desensitize the immune system in the context of allergic disease; however, the only currently approved product is for peanut allergy. ADP101 is a novel, pharmaceutical-grade, multifood oral immunotherapy in development to simultaneously treat single or multiple food allergies, containing allergenic proteins from 15 foods in equal parts by protein weight.</div></div><div><h3>Objective</h3><div>The phase 1/2 Harmony trial (NCT04856865) evaluated efficacy and safety of ADP101 in participants with qualifying allergy to 1 to 5 foods in ADP101, defined as dose-limiting symptoms with a ≤100 mg challenge dose during double-blind, placebo-controlled food challenge (DBPCFC).</div></div><div><h3>Methods</h3><div>Participants were randomized to low-dose (1500 mg/d; 100 mg protein per food) or high-dose (4500 mg/d; 300 mg protein per food) ADP101, or matched placebo, with dose escalation followed by daily maintenance dosing over 40 weeks. The primary endpoint was the proportion of participants tolerating a ≥600 mg challenge dose of a single qualifying food without dose-limiting symptoms at the Week 40 Exit DBPCFC (ie, responders).</div></div><div><h3>Results</h3><div>In the primary analysis population (61 pediatric participants aged 4-17 years), a greater response rate was observed in both the high-dose ADP101 (55.0%) and low-dose ADP101 (38.1%) groups compared with pooled placebo (20.0%) (nominal <em>P</em> = .048, <em>P</em> = .306, respectively; adjusted for multiple comparisons, <em>P</em> = .097, <em>P</em> = .306, respectively). Desensitization to ≥2 foods was observed in individuals with multiple food allergies, as was desensitization at levels over 600 mg. ADP101-treated participants showed an overall reduction in skin-prick test reactivity, with an increase in maximum tolerated dose across the majority of foods tested. Adverse events were mostly mild or moderate, with no life-threatening events or deaths.</div></div><div><h3>Conclusions</h3><div>The study did not meet its primary endpoint, but ADP101 demonstrated a favorable safety profile and increased the reactive threshold in DBPCFC in pediatric participants with single or multiple food allergies across multiple endpoints, warranting further clinical investigation.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 1","pages":"Article 100382"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jacig.2024.100386
Wesley V. Cain DO , Roman A. Jandarov PhD , Mohana Priya SRP, MPH , Marepalli Rao PhD, MS , Jonathan A. Bernstein MD
Background
Omalizumab (OMA), a recombinant humanized IgG monoclonal anti-IgE antibody, is approved for treatment for chronic spontaneous urticaria (CSU) refractory to second-generation H1-antihistamine (SGAH) therapy. However, currently, there are no validated serum biomarkers to reliably predict response to OMA treatment.
Objective
We explored the real-world clinical utility of using serum biomarkers for predicting response to OMA for CSU patients with disease refractory to high-dose SGAH therapy.
Methods
A single-center, retrospective chart review of CSU patients treated with OMA enrolled patients who had at their initial evaluation collection of a basophil histamine release assay for detecting IgG antibodies targeting FcεR1α subunit before starting OMA treatment. In addition, total IgE, IgG–anti–thyroid peroxidase (TPO), C-reactive protein, and absolute eosinophil count, if available, were analyzed as predictors for OMA response. The validated Outcome and Assessment Information Set Database (OASIS-D) rating system was used to assess responsiveness to OMA.
Results
High levels of IgG–anti-TPO were significantly associated with a poor response to OMA. However, basophil histamine release assay, total IgE, C-reactive protein, and absolute eosinophil count, as well as IgG–anti-TPO/total IgE ratios, were not predictive of a response to OMA therapy.
Conclusions
This real-world study confirms previous reports that a high IgG–anti-TPO level is a reliable predictor of poor response to OMA. However, better validation of basophil histamine release assay and other immunoassays that measure IgG antibodies to FcεR1α subunit are required before they can be recommended as predictors for OMA response. Whether any of these biomarkers are relevant for predicting response to novel advanced therapeutics under current development requires further investigation.
{"title":"Utility of serum biomarkers in real-world practice for predicting response to omalizumab therapy in patients with chronic spontaneous urticaria","authors":"Wesley V. Cain DO , Roman A. Jandarov PhD , Mohana Priya SRP, MPH , Marepalli Rao PhD, MS , Jonathan A. Bernstein MD","doi":"10.1016/j.jacig.2024.100386","DOIUrl":"10.1016/j.jacig.2024.100386","url":null,"abstract":"<div><h3>Background</h3><div>Omalizumab (OMA), a recombinant humanized IgG monoclonal anti-IgE antibody, is approved for treatment for chronic spontaneous urticaria (CSU) refractory to second-generation H<sub>1</sub>-antihistamine (SGAH) therapy. However, currently, there are no validated serum biomarkers to reliably predict response to OMA treatment.</div></div><div><h3>Objective</h3><div>We explored the real-world clinical utility of using serum biomarkers for predicting response to OMA for CSU patients with disease refractory to high-dose SGAH therapy.</div></div><div><h3>Methods</h3><div>A single-center, retrospective chart review of CSU patients treated with OMA enrolled patients who had at their initial evaluation collection of a basophil histamine release assay for detecting IgG antibodies targeting FcεR1α subunit before starting OMA treatment. In addition, total IgE, IgG–anti–thyroid peroxidase (TPO), C-reactive protein, and absolute eosinophil count, if available, were analyzed as predictors for OMA response. The validated Outcome and Assessment Information Set Database (OASIS-D) rating system was used to assess responsiveness to OMA.</div></div><div><h3>Results</h3><div>High levels of IgG–anti-TPO were significantly associated with a poor response to OMA. However, basophil histamine release assay, total IgE, C-reactive protein, and absolute eosinophil count, as well as IgG–anti-TPO/total IgE ratios, were not predictive of a response to OMA therapy.</div></div><div><h3>Conclusions</h3><div>This real-world study confirms previous reports that a high IgG–anti-TPO level is a reliable predictor of poor response to OMA. However, better validation of basophil histamine release assay and other immunoassays that measure IgG antibodies to FcεR1α subunit are required before they can be recommended as predictors for OMA response. Whether any of these biomarkers are relevant for predicting response to novel advanced therapeutics under current development requires further investigation.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 1","pages":"Article 100386"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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