Clinical trials in allergen immunotherapy: current concepts and future needs

Pfaar, Oliver; Alvaro, Montserrat; Cardona, Victòria; Hamelmann, Eckard; Mösges, Ralph; Kleine‐Tebbe, Jörg

doi:10.1111/all.13429

Cited by 59 publications

(82 citation statements)

References 61 publications

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“…In all the above‐mentioned scenarios, the nasal allergen challenge (NAC) is a helpful diagnostic tool, as it is the gold standard to establish the clinical reactivity to an allergen and to accurately identify AR and LAR individuals . Furthermore, the NAC is a useful tool for both translational and clinical research studies …”

Section: Introductionmentioning

confidence: 99%

Safety and reproducibility of nasal allergen challenge

Eguiluz‐Gracia

Testera‐Montes

González

et al. 2019

Allergy

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Background:The nasal allergen challenge (NAC) is a useful tool for the diagnosis of allergic rhinitis (AR) and local allergic rhinitis (LAR) and might serve to design and monitor allergen immunotherapy. Nevertheless, data about its safety and reproducibility are scarce.Objective: To investigate the safety and reproducibility of NAC in pediatric and adult rhinitis patients with/without asthmatic symptoms, and in healthy controls. Methods:A retrospective evaluation of the NACs conducted in our Unit for 2005-2017 and monitored by acoustic rhinometry and nasal-ocular symptoms was performed to analyze the safety of two methods for allergen application (metered spray & micropipette) and NAC protocols (NAC with single or multiple allergens/session [NAC-S & NAC-M]). The adverse events (AEs), spirometry values, and rescue medication required for AE were recorded. The reproducibility was examined by a prospective analysis of three repeated NAC-S performed at 1-2-month interval in AR, LAR and nonallergic rhinitis patients, and in healthy controls. Results: A total of 11 499 NACs were performed in 518 children and 5830 adults.Only four local AE occurred, and 99.97% of NACs were well tolerated. The reproducibility and positive and negative predictive values of three consecutive NAC-S performed in 710 subjects were 97.32%, 100%, and 92.91%, respectively. There were no false-positive results in the 710 analyzed subjects. Safety and reproducibility were comparable between the methods of allergen application and the rhinitis phenotypes. Conclusion:The NAC is a safe and highly reproducible diagnostic test ready to be used in the clinical practice in both children and adults with or without asthma. K E Y W O R D Slocal allergic rhinitis, nasal allergen challenge, reproducibility, safety Abbreviations: AE, adverse event; AIT, allergen immunotherapy; AR, allergic rhinitis; DP, Dermatophagoides pteronyssinus; EAACI, European Academy of Allergy and Clinical Immunology; FEV1, forced respiratory volume in the first second; HC, healthy control individual; IQR, interquartile range; LAR, local allergic rhinitis; NAC-M, NAC with multiple allergens per session; NAC, nasal allergen challenge; NAC-S, NAC with a single allergen per session; NAR, nonallergic rhinitis; NHR, nasal hyperreactivity; NPV, negative predictive value; PPV, positive predictive value; sIgE, allergen-specific IgE; SPT, skin prick test; Vol 2-6 cm, volume 2-6 cm of each nostril.Eguiluz-Gracia and Testera-Montes contributed equally to this paper.

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Section: Introductionmentioning

confidence: 99%

Safety and reproducibility of nasal allergen challenge

Eguiluz‐Gracia

Testera‐Montes

González

et al. 2019

Allergy

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“…An increasing number of AIT products fulfill the regulatory demands and have been authorized in different countries on the basis of proven efficacy in the clinical documentation . However, the regulatory guidance leaves some space for interpretation regarding certain specificities of clinical trial design in both early and late phases of clinical development programs for AIT, and harmonization of methodological principles in the design of these trials would be preferable for all parties involved . Hence, the Immunotherapy Interest Group (IT‐IG) of the European Academy of Allergy and Clinical Immunology (EAACI) has elaborated different task‐force projects regarding improvement of methodological study design in AIT (https://www.eaaci.org/organisation/eaaci-interest-groups/ig-on-immunotherapy/activities/2880-task-forces-of-the-immunotherapy-interest-group.html; accessed on 07 Dec 2018).…”

Section: Diagnostic Challenges and Regulatory Considerationsmentioning

confidence: 99%

“… Evaluation and validation of possible biomarkers of predictive value for efficacy Further validation of clinical meaningful primary and secondary endpoints Clinically justified definitions of relevant treatment effect sizes Potential of allergen exposure chambers for AIT product development Minimal level of evidence needed for the clinical documentation of efficacy in the pediatric population Better understanding of placebo effects in SCIT and SLIT Defining clinical endpoints and establishing the effectiveness, disease‐modifying properties, and the duration of both in asthmatic patients …”

Section: Diagnostic Challenges and Regulatory Considerationsmentioning

confidence: 99%

“…However, for further expansion of AIT, we must influence the balance between allergenicity and immunogenicity, which can improve both duration of treatment and create a better side effect profile. Furthermore, we need greater understanding of the molecular mechanisms underlying the development of respiratory allergic disease and of AIT at the level of the individual patient, facilitating better patient stratification for AIT to further improve optimal personalized treatment Research needs for novel AIT vaccines Short, effective, and safe treatment Prediction of individual success before or early during the treatment Better understanding of the underlying molecular and immunological mechanisms Optimal AIT clinical trials that reduce bias and heterogeneity Collaboration between physicians, patient organizations, companies, and regulators …”

Section: Unmet Needs and Future Research Areas In Treatment Of Allergmentioning

confidence: 99%

“…of respiratory allergic disease and of AIT at the level of the individual patient, facilitating better patient stratification for AIT to further improve optimal personalized treatment. 16,107…”

Section: Novel Therapeutic Concepts In Ait For Airway Diseasementioning

confidence: 99%

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Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

Breiteneder

Diamant

Eiwegger

et al. 2019

Allergy

Self Cite

101

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This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. AbstractThe specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted treatment options, including biologicals and small molecules.This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring Zuzana Diamanthttps://orcid.org/0000-0003-0133-0100Thomas Eiwegger https://orcid.org/0000-0002-2914-7829Wytske J. Fokkens https://orcid.org/0000-0003-4852-229X

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International consensus statement on allergy and rhinology: Allergic rhinitis – 2023

Wise

Damask

Roland

et al. 2023

Int Forum Allergy Rhinol

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Background In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR‐Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR‐Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence‐based findings and recommendation from the full document. Methods ICAR‐Allergic Rhinitis 2023 employed established evidence‐based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results ICAR‐Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion The ICAR‐Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

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Clinical trials in allergen immunotherapy: current concepts and future needs

Cited by 59 publications

References 61 publications

Safety and reproducibility of nasal allergen challenge

Safety and reproducibility of nasal allergen challenge

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

International consensus statement on allergy and rhinology: Allergic rhinitis – 2023

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