Omalizumab has been shown to increase reaction thresholds to allergenic foods during treatment. Little is known about its potential to permit introduction of allergenic foods.

To study the introduction of allergenic foods after stopping treatment with omalizumab.

The first 60 participants completing OUtMATCH Stage 1 entered a 24-week open-label extension, followed by entry into protocol Stage 3, which could include dietary allergen consumption (DC), rescue oral immunotherapy, or allergen avoidance, depending on the results of the final food challenges and participant preferences.

Sixty participants were included (58% male, median age 8.5 years, range 1–20 years). Foods included peanut (n=60), cashew (n=28), egg (n=27), milk (n=25), walnut (n=23), wheat (n=9), and hazelnut (n=8). 82% of initial treatment plans included DC. DC success was defined as a median daily consumption of ≥300 mg food protein over 12 months, with data analyzed in quarterly intervals. Overall greater success was observed for milk/egg/wheat (61–70%) compared to peanut/tree nuts (38–56%). Allergenic food consumption generally declined over time, except for wheat, with greater variability in median consumption for egg/milk relative to nuts. Reduced consumption appeared to be related to both symptoms and patient preference. The only predictor of DC success was a higher screening challenge threshold. Adverse events included episodes of anaphylaxis, epinephrine use, and 2 EoE diagnoses related to DC.

In this first study of retail food introduction following omalizumab treatment, most participants were able to introduce allergenic foods in a dietary form, although adverse reactions did occur and many participants returned to avoidance.

Oral immunotherapy (OIT) is a promising treatment for food allergies. However, the molecular mechanisms leading to desensitization remain unknown. To better understand the immunological mechanisms and transcriptional changes underlying desensitization to food allergens during OIT.

Our cohort consisted of 40 Finnish children with egg allergy who underwent OIT. Peripheral blood mononuclear cells (PBMCs) were collected at 0, 3, and 8 months of therapy and stimulated with an egg allergen extract. Differentially expressed genes (DEGs) were identified based on quantile-normalized and batch-corrected microarray data using a linear model. Gene enrichment and Pearson correlation analyses were conducted.

After 8 months of therapy, 45% of patients were fully desensitized and 55% partially desensitized. Stimulation with egg yielded 49 DEGs at 0 months, 723 DEGs at 3 months, and 759 DEGs at 8 months in PBMCs after comparison with unstimulated controls. At 8 months of OIT, allergen stimulation led to downregulation of proinflammatory pathways, as well as IL-4 and IL-13 signaling. At baseline, the immune response in the fully desensitized group was more reactive than in the partially desensitized group.

During OIT, general immune activity is increased, especially the number of down-regulated genes, suggesting active immune suppression. Transcriptomic profiles differ between fully and partially desensitized patients, with a notably more reactive immune response in the fully desensitized group at baseline. Innate immunity seems to play a significant role in the development of desensitization during OIT.

House dust mite (HDM) allergies are prevalent, yet current treatments like allergen avoidance, pharmacotherapy, and conventional allergen immunotherapy present limitations. The novel LAMP (lysosomal-associated membrane protein)-based DNA vaccine ASP2390 targets major HDM allergens, potentially shifting immune responses toward nonallergic pathways and minimizing the risk of atopy, with positive safety and efficacy signals in preclinical models.

We evaluated the safety, tolerability, and efficacy of first-in-human intradermal ASP2390 in adults with HDM allergy.

A randomized, double-blind, placebo-controlled phase 1 trial was conducted in adults with HDM-induced allergic rhinitis. Participants received either 1 mg or 4 mg of ASP2390 or placebo intradermally once weekly for 12 weeks, with safety, tolerability, and pharmacodynamic responses assessed over a 63-week period, including early-phase clinical effects assessed via HDM exposure in an allergen challenge chamber.

Twenty-eight adults (mean age, 26.9 years; 23 male participants), with 7 receiving 1 mg and 13 receiving 4 mg ASP2390, 8 receiving placebo, showed no serious adverse events or withdrawals due to treatment-emergent adverse events. The most common events were nasopharyngitis, coronavirus disease 2019, headache, fatigue, and diarrhea; fatigue and headache were the most frequent systemic reactions, and injection-site tenderness the most frequent local reaction. There were no substantial changes in allergen-specific immunoglobulin levels, basophil activation, or T helper cell subpopulations, and no difference in allergic clinical responses compared to placebo.

Intradermal DNA vaccine ASP2390 is safe and well tolerated but does not show an immunologic or clinical response in a small sample of adults allergic to HDM.

Food allergen immunotherapy (FAIT) is a consolidated treatment included in clinical guidelines that has shown efficacy in terms of researcher-defined variables, but little work has been done yet to evaluate patients’ perspectives.

We aimed to understand and explore the relevance of different patient-reported outcomes (PROs).

An EAACI Taskforce designed a questionnaire to prospectively collect information from parents or caregivers of patients below 18 years on FAIT. Participants from North America and several European countries were invited to provide data regarding socioeconomic aspects, allergic background, FAIT modality, burden, safety, and food allergy quality of life (FAQoL). As primary outcome, 19 proposed PROs were ranked according to their relevance (5-point Likert scale). A descriptive and cluster analysis of the data was performed.

84 FAIT prescribers recruited 857 patients suitable for analysis, 41.5%, 39.7%, and 18.8% were on milk, peanut, and egg AIT, respectively. Patients were grouped into regions: South Europe (46.2%), North America (24.3%), Western Europe (20.7%), and United Kingdom (8.9%). Total FAQoL questionnaire score was 4.1 (±SD 1.4), significantly higher among South Europeans [4.7 (±SD 1.3), p < 0.0001]. Worse FAQoL scores were found for milk and egg FAIT vs peanut. Cluster analysis identified 5 different phenotypes of patients considering similar replies to the proposed PROs, labeled: "High expectations," "Beyond protection," "Social Functioning," "Aiming at normalization," and "Low motivations."

The data-driven analysis provided novel information on the level of complexity and personalization that patients’ desires display and opens the field to future research lines to improve FAIT patient-perceived value.

Allergic rhinitis (AR) is a global health concern with an increasing prevalence. Among them, pollen-induced AR (PIAR) exhibits more severe and intense symptoms, decreased quality of life, prominent local inflammation, and is thus more challenging to control. Due to the difficulties in disease control, in recent years, an increasing number of treatment methods, including pharmacotherapy, allergen-specific immunotherapy, and newly developed biologics, have focused on PIAR. It has been shown that the pollen exposure has a significant impact on the symptoms of PIAR and the efficacy of intervention. From this perspective, clinical trials for PIAR need to take full account of pollen exposure, especially when assessing efficacy.

This review summarized the effect of pollen exposure on PIAR, including immune responses, symptoms, and clinic visits. Current definitions for the pollen season (PS) and the peak pollen season (PPS) are discussed. Based on the previous PIAR-related clinical studies and the available recommendations for clinical trial design, a detailed account of trial protocols which fully considered pollen exposure is provided.

Pollen exposure has a significant impact on PIAR. With fully considering the pollen exposure in the clinical trial design for PIAR, future protocols for PIAR-related studies may be more objective and better harmonized and, therefore, comparable.

Patients with atopic dermatitis (AD) are frequently sensitised to house dust mites (HDM). While Dupilumab is effective, the role of subcutaneous immunotherapy (SCIT) remains unclear. This study evaluated the safety and clinical outcomes of combined Dupilumab and SCIT in HDM-sensitised AD patients. In this retrospective study, 47 adults with HDM-sensitised AD received concurrent Dupilumab and HDM-SCIT for 48 weeks. Eczema Area and Severity Index (EASI) scores, total and HDM-specific IgE levels were monitored. Safety was assessed by adverse events related to SCIT and Dupilumab. EASI scores improved significantly from baseline (28.4 ± 6.9) to Week 12 (14.8 ± 4.5), Week 24 (12.7 ± 4.3) and Week 48 (5.2 ± 2.8). HDM-specific IgE (d1, d2) and total IgE decreased by Week 48 (p < 0.05). SCIT-related local and systemic reactions declined over time. Dupilumab-related conjunctivitis, head and neck dermatitis, and upper respiratory tract infections were transient and reduced during follow-up. The combination of Dupilumab and SCIT was well tolerated and associated with clinical improvement and IgE reduction in HDM-sensitised AD patients. These findings support further investigation in prospective controlled trials.

The aim of MASK-air® application is to enhance awareness of allergic rhinitis (AR) and its complications, thereby reducing the risk of developing asthma.

A prospective cross-sectional study was conducted between August and November 2019 at a tertiary Allergy and Immunology center involving patients receiving AIT. Participants were instructed on accessing and utilizing MASK-air® daily through face-to-face interviews. Concurrently, the Score for Allergic Rhinitis (SFAR) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were administered alongside MASK-air® Visual Analog Scale (VAS) scores. After 6 months, RQLQ scores were reassessed and a satisfaction survey was conducted.

This study comprised 96 patients. Significant correlations were observed among SFAR, RQLQ, and VAS scores. After 6 months of MASK-air® usage, improvements in QoL and symptom reduction were evident. Notably, participants who consistently used MASK-air® demonstrated significant reductions in activity limitations and hay fever scores compared to irregular users (p = 0.05 and p = 0.02, respectively). Additionally, participants under 40 years of age and those with higher education levels exhibited a greater inclination toward online monitoring via the application. Overall, participants found MASK-air® practical, citing various advantages and disadvantages.

MASK-air® serves as a valuable tool for physicians in managing treatment and is associated with validated, reliable scales. Its use was linked to enhanced QoL and symptom reduction among participants, irrespective of treatment duration.

Food allergies are common, affecting a sizable portion of children and adults in the Western world. In recent years, a promising treatment known as allergen immunotherapy (AIT) has emerged. This technique aims to address the fundamental immune system dysfunction that underlies food allergies. The study's objective was to evaluate the safety of combining probiotics with AIT, compared to placebo in treating patients with food allergies. A comprehensive literature search in several databases was conducted. All included studies were randomized controlled trials (RCTs). Meta-analyses were performed using R software. Statistical tests to assess safety outcomes and risk of bias were used. After reviewing 519 studies, three studies were included in the systematic review and meta-analysis, involving a total of 258 patients (141 in the probiotics group, 144 in the placebo group). The evaluation of the safety profile of the integrated probiotic therapy revealed an overall favorable outcome, with no significant differences in adverse events compared to placebo for most organ systems examined. However, a potential increase in oral adverse effects was observed in the probiotics group (RR = 1.7573, 95% CI: 0.3941 to 7.8359), although this result did not reach statistical significance. The combination of probiotics and allergen-specific immunotherapy appears to be generally safe and shows promise as a valuable treatment approach.

Gliadins are the primary triggers in wheat-dependent exercise-induced anaphylaxis. Currently, there are no officially approved immune-modulating treatments for gliadin allergy. Recent in vivo studies have shown that hyaluronic acid–based dissolving microarray patch (dMAP) could deliver house dust mite allergens through the transdermal pathway and protect against allergic asthma and atopic dermatitis in vivo. In this study, we explored the potential of dMAP for the transdermal delivery of gliadin proteins as a strategy to mitigate gliadin allergy.

C3H/HeJ mice were sensitized to gliadin with cholera toxin via oral administration, followed by oral or intraperitoneal gliadin challenge. To evaluate the protective effects of transdermal immunotherapy (TDIT), gliadin-loaded dMAPs were applied twice a week to gliadin-sensitized mice for 4 weeks. Afterward, the mice were challenged with gliadin.

The manufacturing process of dMAP did not alter the allergenicity of gliadin. TDIT significantly improved the anaphylaxis clinical score and stabilized core body temperature in the gliadin anaphylaxis model. It reduced mast cell protease-1 and gliadin-specific immunoglobulin E (IgE), and increased specific IgG₁, IgG2a, and IgG2b levels. Ex vivo splenocyte study revealed that TDIT enhanced T helper type 1 (Th₁) cell population, interferon-γ expression, regulatory T cell population, and interleukin (IL)-10 expression, as well as suppressed Th₂ cell population and associated cytokines (IL-4, IL-5, and IL-13). Furthermore, this TDIT preserved the structural integrity of small intestinal villi and reduced eosinophil and mast cell infiltration.

Gliadin TDIT using dMAP mitigates gliadin-induced anaphylaxis in a murine model, offering a promising novel immune-modulating treatment for gliadin-induced anaphylaxis.

There is an important heterogeneity of the clinical research done to date for allergen immunotherapy (AIT). We plan to assess the safety and efficacy of a house dust mite (HDM) polymerized allergen extract mixture for allergic rhinoconjunctivitis (AR) according to both the EMA and European Academy of Allergy and Clinical Immunology (EAACI) guidelines for the clinical development of products for the treatment of AR.

We will perform a double-blind, placebo-controlled, randomized parallel group phase III clinical trial to assess the clinical efficacy and safety of a polymerized Dermatophagoides pteronyssinus and Dermatophagoides farinae allergen extract mixture (Beltavac®) to treat perennial AR in children and adults. Patients with moderate or severe rhinitis symptoms, either associated or not with asthma and confirmed HDM sensitization and without relevant concomitant conditions that may interfere with the planned evaluations test are eligible. Patients will be randomized in a 1:1 ratio to either the active AIT or placebo. The experimental group will receive 12 monthly AIT doses via subcutaneous route with a potency of 2 RC/ml per allergen. The expected sample size is 250 patients from 16 sites in Spain. The main efficacy outcome is the Combined Symptom and Medication Score (CSMS) for rhinitis. It will be patients' self-assessed and collected through a phone App developed ad hoc for the study to improve the patient adherence and the quality of data. Main secondary outcomes include expanded CSMS for rhinoconjunctivitis symptoms, control of rhinitis, specific IgE and IgG4 values, quality of life, and the number of adverse reactions. Health-related direct and indirect costs will be also evaluated. Finally, several exploratory parameters will be used to assess the severity of asthma.

This phase III clinical trial will be of interest to contribute to the scientific evidence about the efficacy and safety of AIT with allergoids. Our working hypothesis is that the investigational product in patients with AR associated or not with asthma is superior to placebo in providing a clinically significant improvement according to the standards defined by the EAACI. This trial will also supply valuable information about patients reported outcomes using health technology for rhinoconjunctivitis and asthma assessment.