Multiomics approach to evaluating personalized biomarkers of allergen immunotherapy.

Recent advancements in genomics and "omic" technologies have ushered in a transformative era referred to as personalized or precision medicine. This innovative approach considers the unique genetic profiles of individuals, along with a range of variability factors, to devise tailored disease treatments and prevention strategies that cater to the distinct needs of each patient. Although the terms personalized medicine and precision medicine are frequently utilized interchangeably, it is essential to delineate the subtle distinctions between them.

The Minimal Clinically Important Difference in Allergen Immunotherapy: An Evidence-Based Approach.

Background: Regulatory authorities recommend a combination of symptom and medication scores during the grass pollen season as a primary endpoint for Phase III allergen immunotherapy (AIT) trials targeting allergic rhinoconjunctivitis. However, many composite primary endpoint scales exist; none are validated, nor do they have a well-justified minimal clinically important difference (MCID).

Methods: Direct patient feedback from 1071 grass-allergic patients was obtained to determine the minimally relevant improvement in allergic symptoms and translated into an MCID for the EAACI recommended CSMS.

Modulation of Cellular, Molecular, and Humoral Responses by PQ Grass 27,600 SU for the Treatment of Seasonal Allergic Rhinitis: A Randomised Double Blind Placebo Control Exploratory Field Study.

Background: A short-course pre-seasonal subcutaneous injection of PQ Grass is clinically effective for the treatment of allergic rhinitis, though its mechanism remains unclear. The aim of the study was to interrogate immunological mechanisms induced by PQ Grass conventional and extended regimens.

Methods: A RDBPC exploratory field study involving participants that either received injections of PQ Grass with a cumulative dose of 27,600 SU conventional (six once weekly injections) or extended regimen (three once weekly injections followed by three once monthly injections) or placebo containing microcrystalline tyrosine (MCT) (placebo + MCT) or saline (placebo) was performed.

Mechanisms and Treatment of Type 2 High and Low Asthma Endotypes.

Asthma is a complex, heterogeneous disease characterised by clinical phenotypes demonstrating distinct and overlapping immunological mechanisms, classified into type-2 high and type-2 low asthma endotypes. Both allergic and eosinophilic non-allergic asthma are driven through an underlying type-2 high-endotype, which can be targeted using therapeutic approaches such as allergen-specific immunotherapy (AIT) for allergic asthma and biologics. AIT demonstrates efficacy for the treatment of allergic asthma.

Oral Immunotherapy in Peanut-Allergic Adults Using Real-World Materials.

Background: Peanut oral immunotherapy (OIT) has shown effectiveness in achieving desensitization of children; however, evidence in adults is lacking.

Methods: This phase II trial evaluated peanut OIT in peanut-allergic adults using real-world peanut products. A Simon's minimax two-stage design, incorporating a stop:go for futility, was employed.

Biomarker-driven drug development for allergic diseases and asthma: An FDA public workshop.

The US Food and Drug Administration (FDA) hosted a workshop on February 22, 2024, to discuss the status of biomarkers in drug development for allergic asthma and food allergy. The workshop provided a forum for open discussion among regulators, academicians, National Institutes of Health staff and industry to inform stakeholders of the requirements for the FDA to adopt a biomarker as a surrogate end point for a clinical trial, and to inform FDA of the status of various biomarkers in development. The workshop was divided into 3 sessions: (1) FDA and European Union regulators discussing regulatory perspectives on use of biomarkers in drug development programs, (2) investigators discussing biomarkers for pediatric and adult asthma, and (3) investigators discussing biomarkers for food allergy.

Six Injections of Modified Adjuvanted PQ Grass Is Effective and Well-Tolerated in a Pivotal Phase III Trial.

Background: PQ Grass 27600 SU (PQ Grass) cumulative dose is a pre-seasonal, six-injection, aluminium-free, modified subcutaneous immunotherapy product under development for the treatment of allergic rhinitis (AR). A pivotal Phase III randomised double-blind, placebo-controlled clinical trial was performed to evaluate the efficacy and safety of PQ Grass in subjects with seasonal AR.

Methods: An adaptive group sequential trial PQGrass306 (G306) with one pre-defined interim analysis was designed, using 2 parallel groups applying a 1:1 active versus placebo randomisation of patients aged 18-65.

IL-25 Enhances B Cell Responses in Type 2 Inflammation Through IL-17RB Receptor.

Background: Alarmin cytokine IL-25 promotes type 2 inflammatory responses in disorders such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and known targets include ILC2 and Th2 cells. However, other cellular targets for IL-25 remain poorly defined.

Objective: To investigate induction and expression of IL-25 receptor (IL-17RB) by B cells and evaluate responsiveness of IL-17RB-expressing B cells to IL-25 in vitro.

Ara h 2-expressing cucumber mosaic virus-like particle (VLP Peanut) induces in vitro tolerogenic cellular responses in peanut-allergic individuals.

Background: Peanut allergy (PA) is one of the most prevalent food allergies with a lack of favorable safety/efficacy treatment. A cucumber mosaic virus-like particle expressing peanut allergen component Ara h 2 (VLP Peanut) has been developed as a novel therapeutic approach for PA.

Objective: We assessed the tolerogenic properties and reactivity of VLP Peanut.

Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study.

Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses.

Allergen Immunotherapy for the Prevention and Treatment of Asthma.

Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies.

Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.

Background: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined.

Methods: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors.

Relevance of individual bronchial symptoms for asthma diagnosis and control in patients with rhinitis: A MASK-air study.

Rationale: It is unclear how each individual asthma symptom is associated with asthma diagnosis or control.

Objectives: To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control.

Methods: In this cross-sectional study, we assessed real-world data using the MASK-air app.

Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making.

Nasal allergen-neutralizing antibodies correlate closely with tolerated intranasal allergen challenge dose following grass pollen subcutaneous immunotherapy in patients with local allergic rhinitis.

Background: Local allergic rhinitis (LAR) is defined by chronic nasal symptoms, absence of atopy, positive nasal allergen challenge (NAC) and a good response to subcutaneous allergen immunotherapy (SCIT). We sought to investigate SCIT capacity to induce local and systemic blocking antibodies in LAR patients.

Methods: A RDBPC study of grass SCIT was performed, with participants receiving either SCIT (Group A; n = 10) or placebo (Group B; n = 14) in the first 6 months.