Randomized controlled trials have demonstrated the efficacy of allergy immunotherapy (AIT) in allergic rhinitis (AR) and the disease-modifying effects of the SQ grass sublingual immunotherapy (SLIT) tablet.

We sought to assess real-world, long-term effectiveness and safety across AIT subgroups: route of administration, therapeutic allergen, persistence to AIT, and SQ grass SLIT tablet.

The primary outcome of AR prescriptions from a retrospective cohort study (REAl-world effeCtiveness in allergy immunoTherapy; 2007-2017) was assessed across prespecified AIT subgroups in subjects with AR with and without AIT prescriptions (controls). Safety was assessed as anaphylaxis for 2 days or less of the first AIT prescription. Subgroup follow-up continued until samples were fewer than 200 subjects.

Subcutaneous immunotherapy (SCIT) and SLIT tablets showed similarly greater reductions in AR prescriptions than controls (SCIT vs SLIT tablets: year 3, P = .15; year 5, P = .43). Comparably greater reductions in AR prescriptions were observed for grass- and house dust mite-specific AIT than for controls, but significantly smaller reductions were observed for tree-specific AIT (tree vs house dust mite, and vs grass: years 3 and 5, P < .0001). Persistence to AIT was associated with greater reductions in AR prescriptions versus nonpersistence (persistence vs nonpersistence: year 3, P = .09; year 5, P = .006). SQ grass SLIT tablet showed sustained reductions versuscontrols for up to 7 years (year 3, P = .002; year 5, P = .03). Rates of anaphylactic shock were low (0.000%-0.092%), with no events for SQ SLIT tablets.

These results demonstrate real-world, long-term effectiveness of AIT, complement disease-modifying effects observed in SQ grass SLIT-tablet randomized controlled trials, and highlight the importance of using newer evidence-based AIT products for tree pollen AR.

We aimed to compare the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) with standardized house dust mite (HDM) extract for allergic rhinitis.

Participants with allergic rhinitis selected their treatment between HDM SCIT or HDM SLIT, according to their wishes. We prospectively followed symptoms of allergic rhinitis using the alergic rhinitis symptom medication score (ARSMS), along with adverse reactions, during the dose escalation and maintenance phases for two years. We compared the outcomes between propensity scorematched groups to adjust the confounding factors.

After propensity score matching, 88 patients in the HDM SCIT(n = 44) and HDM SLIT groups (n = 44) remained for analysis. The HDM SCIT group showed significantly earlier effectiveness than the HDM SLIT group (median time to decrease in ARSMS [≥2 points]: 5.5 vs. 18.0 months, p < 0.001). The incidence of systemic reactions was not significantly different between the two groups in the dose escalation phase (68.2% vs. 56.8%, p = 0.379). In the maintenance phase, the incidence of systemic reactions was higher in the HDM SCIT group than in the HDM SLIT group (18.2% vs. 0%, p < 0.006). All 44 patients in the HDM SCIT group completed two years of treatment, while nine patients in the HDM SLIT group discontinued treatment.

Epicutaneous immunotherapy (EPIT) with investigational Viaskin™ Peanut 250 μg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut-allergic children in clinical trials. It is unclear if serologic biomarkers predict response.

Serum-specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 PEPITES study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double-blind placebo-controlled food challenge.

Among Viaskin Peanut-treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (P 20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE <15.7 kUA /L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥300 mg) and 67.8% (ED ≥1000 mg).

Peanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios >20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships.

Subcutaneous immunotherapy (SCIT) is a well-validated and effective disease modification treatment for house dust mites (HDM)-induced allergic rhinitis (AR). Long-term post-treatment comparisons in children and adults treated with SCIT have rarely been published. This study aimed to evaluate the long-term efficacy of HDM SCIT administered under a cluster schedule in children compared to adults.

This was an open-design, observational, long-term clinical follow-up study on children and adults with perennial AR treated with HDM-SCIT. The follow-up consisted of a three-year treatment duration plus a post-treatment follow-up of over three years.

Patients in the pediatric (n = 58) and adult (n = 103) groups completed a post-SCIT follow-up of over three years. The total nasal symptom score (TNSS), combined symptom medication score (CSMS), and rhinoconjunctivitis quality-of-life questionnaire (RQLQ) score decreased significantly at T1 (three-year SCIT completed) and T2 (follow-up completed) in the pediatric and adult groups. In both groups, the improvement rate of TNSS (T0-T1) was moderately correlated with the baseline TNSS (r = 0.681, p < 0.001 and r = 0.477, p < 0.001 for children and adults, respectively). Only in the pediatric group, TNSS was significantly lower at T2 compared with that right after SCIT cessation (T1) (p = 0.030).

Children and adults with HDM-induced perennial AR could achieve a sustainable post-treatment efficacy for over three years (up to 13 years) following a three-year SCIT. Patients with relatively severe nasal symptoms at baseline may benefit more from SCIT. Children who have completed an adequate course of SCIT may gain further improvement in nasal symptoms after SCIT cessation.

The composition of venom extracts, cross-reactive carbohydrate determinants (CCD) and the component-resolved diagnostics (CRD) are important fields of investigation. IgE-reactivity to CCD complicates the interpretation of IgE to Hymenoptera venoms, especially in patients with multiple-positivity. We analyzed the clinical importance of CRD and CCD-inhibition for selection of allergens for venom immunotherapy (VIT).

In 71 patients, we measured specific IgE (sIgE) to honeybee venom (HBV), wasp venom (WV), hornet venom (HV), CCD, and recombinant allergens: phospholipase A2 (rApi m 1), hyaluronidase (rApi m 2), icarapin (rApi m 10), antigen 5 (rVes v 5), and phospholipase A1 (Immunoblot). In 29/71 HBV/WV/HV/CCD-positive patients CCD-inhibition was performed. According to CRD and CCDinhibition, we identified true sensitization and defined groups of multiple-positive patients who needed CCD-inhibition before starting VIT.

sIgE-rApi m 1, sIgE-rApi m 2, and sIgE-rApi m 10 were detected in 65.7%, 68.4%, and 58%, respectively. In HBV allergic patients, CRD sensitivity was 86.8%. In WV allergic patients, sensitivity of sIgE rVes v 5 was 94%. True multiple-sensitization was found in 44.8% of HBV/WV/HV/CCD-positive patients after CCD-inhibition. Patients with multiple venom- and CCD-positivity had more frequent severe allergic reactions (p < 0.001). CCD-inhibition was helpful in HBV/WV/HV/CCD-positive patients who were negative to all tested recombinant honeybee allergens. Persistence of HBV-positivity after CCD-inhibition requires CRD to other honeybee recombinant allergens.

CRD, using a profile of five most important recombinant allergens and CCD, has a high sensitivity for the diagnosis of venom allergy, especially in patients positive to several venom extracts. CRD and CCD-inhibition are helpful to reveal the clinically relevant, true sensitization and improve the selection of venoms for long-lasting VIT.

The specificity of extract-based pollen allergy diagnosis is decreased due to cross-reactivity via cross-reactive carbohydrate determinants (CCDs) or panallergens such as profilins or polcalcins. This study aimed to explore the prevalence of sensitization to seasonal extracts, CCDs, profilin and polcalcin and investigate the sensitivity and specificity of seasonal molecular allergy diagnosis (MAD) using commercially available test methods.

2948 patients were screened for specific immunoglobulin E to ash, birch, mugwort, ragweed and timothy grass pollen extracts and grouped according to the number of positive tests (1-5). 100 patients from each group and a control group were randomly selected to calculate the prevalence of CCD and panallergen sensitization. With 742 patients, sensitivity and specificity of MAD (Alt a 1, Fra/Ole e 1, Bet v 1, Phl p 1, Art v 1, and Amb a 1) was determined.

1627 patients (55.2%) were positive to at least one, and 1002 patients (34.0%) were positive to multiple of the five pollen allergens investigated; 18.5% of the pollen-sensitized patients had sensitization to CCDs or panallergens. Specifically, sensitization to CCDs, profilins, and polcalcins was observed in 8.7%, 10.9%, nd 2.9% of these patients, respectively. The sensitivity of MAD was high, with sensitivities between 96.2% and 100% using ImmunoCAP and 91.5% and 100% using ALEX2. Specificity was 100% for both assays.

Due to cross-reactivity, about one-fifth of pollen-sensitized patients is at risk of misdiagnosis. However, MAD is sensitive, specific and helps to avoid misdiagnosis and select primary allergen sources for immunotherapy.

Allergen immunotherapy (AIT) as a validated, disease-modifying treatment is nowadays a widely recommended therapy option for allergic rhinitis and allergic asthma. The registration of allergen extracts used for AIT is based on allergen standardization, dose finding trials, and phase 3 trials proving their efficacy in high-quality, statistically significant randomized clinical trials. Real-world evidence (RWE) studies confirm the clinical relevance of these findings. The most data are available for the treatment of patients suffering from allergic rhinitis. Due to the similar inflammatory mechanisms, allergic rhinitis is often associated with allergic asthma. AIT, which induces tolerance against individual allergens, is the approach to treat the underlying mechanisms of these two interrelated respiratory diseases. Some trials have been published focusing primarily on the effect of AIT on parameters of allergic asthma. Here we give a summary of the evidence for the efficacy of AIT in the indication of allergic asthma.

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.

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.

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.

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.

Allergic rhinitis affects approximately 10-20% of people living in industrialized nations leading to significant morbidity and large health care expenditures. Individualized high-dose, single species allergen immunotherapy has been shown to be effective in treating allergic rhinitis but can be associated with significant risks including anaphylaxis. Few studies have examined the safety and efficacy of universal low-dose multi-allergen immunotherapy.

To determine the efficacy and safety of a universal, multi allergen immunotherapy formula for the treatment of allergic rhinitis.

Patients with moderate-severe perennial and seasonal allergic rhinitis were randomized in a double-blind, placebo-controlled fashion to receive a novel, subcutaneous multi-allergen immunotherapy (MAIT) regimen containing a unique mixture of more than 150 aeroallergens, including several cross-reactive species. All patients received the exact same universal immunotherapy formula regardless of which specific skin tests were positive. Primary outcome measures at 8 and 12 weeks of therapy included validated clinical assessments; TNSS and mini-RQLQ, and the use of rescue medications.

Thirty-one subjects (n=31) were randomized to receive multi allergen immunotherapy (MAIT) versus placebo. By week twelve, MAIT resulted in a -4.6 (-58%) decrease in the combined TNSS and rescue medication score (DCS) compared to -1.5 (-20%) for placebo (P = 0.037). Likewise, MAIT resulted in a mini-RQLQ decrease of -34.9 (-68%) compared to -17 (-42%) for placebo (P = 0.039). Mild adverse events were uncommon and with similar frequency among the groups.

A novel and universal, high species abundance, multi-allergen immunotherapy formula was well-tolerated and resulted in significant improvement in symptoms of moderate-severe allergic rhinitis. The results of this pilot study should be considered preliminary, pending further randomized clinical trials.

Food allergy remains a common problem and a lifelong condition for many children. In recent years food allergy management has increasingly involved conversations about food oral immunotherapy. While ethical considerations of autonomy, beneficence, non-maleficence, and justice implicitly inform these conversations, applying these principles can be complex, particularly in young children. Families of young children assume a role of surrogate decision maker and must balance immediate risks with the hope of longer-term benefits.

To explore implementation of oral immunotherapy in children through an ethical lens.

To evaluate OIT through an ethical lens, a literature search was conducted to explore currently published frameworks in this arena.

Evaluation of the harm principle, the basic interest principle, and the best interest principle of parental decision making can be informative. Shared decision making continues to be central to the process of engaging with patient-family units to individualize the best care, at the right time, and minimize decisional discord. Whie OIT is well positioned to promote health and well-being, challenges to equity, sustainability, and organizational support must be considered to improve access for appropriate patients.

While approaches to food OIT may be tailored to the individual context of each patient-family unit, ethical principles must guide decisions to initiate and continue therapy. Traditional ethical principles of autonomy, beneficence, non-maleficence, and justice remain cornerstones when considering the ethical context of OIT.