Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT and consequently, a lack of information on how AIT effectively works in real life. To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will usethe RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic “real-world” database using systematic data collection.Based on the current RWE base,and perspectives and recommendations of authorities and scientific societies, a hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence. There is a need to establish more AIT registries that collect data in a cohesive way, using standardised protocols. This will provide an essential source of real-world data that can be easily shared, promoting evidence-based research and quality improvement in study design and clinical decision-making.

The purpose of this review is to evaluate the cost-effectiveness of allergy immunotherapy (AIT) in the treatment of allergic rhinitis, asthma, and other allergic conditions.

An extensive search of the PubMed and Medline database (January 1996 up to June of 2020) was conducted using the search terms allergy immunotherapy, pharmacoeconomics, cost-effectiveness, allergic rhinitis, and asthma. Studies were included if they included information on the economics of AIT in comparison to pharmacotherapy in the treatment of allergic rhinitis or asthma either as actual costs or based on theoretical models. Systematic reviews were included if they included information about the cost-effectiveness of AIT.Most clinical trials found significant cost-savings with AIT. The cost-effective time-point ranged from a few months to several years after treatment initiation.. Cost savings were demonstrated as early as 3 months after treatment initiation and were as great as 80% less than SDT in some studies.

There is strong evidence in the collective literature that AIT is cost-effective as compared to SDT alone. The magnitude of AIT’s cost-effectiveness is likely underestimated because most of the studies considered during treatment costs and not AIT’s long-term benefits or preventive/prophylactic effects or its impact on co-morbid conditions.

To date, there are no generally recognized biomarkers for allergen immunotherapy (AIT) and even the changes in immunological indicators during AIT are inconsistent in different publications.

This study was conducted to quantify the immunological changes that occur during AIT and identify the determinants of heterogeneity.

Randomized controlled trials of AIT published in the past 10 years were searched in Medline, Embase and Cochrane CENTRAL. Data on immunological indicators were extracted, and the characteristics of the included studies were collected. Meta-analysis and meta-regression were conducted for each indicator. The study was registered on the PROSPERO website (CRD42020176127).

We reviewed 1898 studies. Forty-six studies met the inclusion criteria, and 31 studies were included in the quantitative analyses. Subset analyses by time demonstrated that serum allergen-specific IgE (sIgE) of AIT patients increased in the first 12 months, then decreased and became slightly lower than that of control patients. Allergen-specific IgG4 (sIgG4) was elevated in the AIT group during and after treatment. IgE-blocking factor (IgE-BF) was increased and IgE-facilitated allergen binding (IgE-FAB) was reduced in AIT patients. Both of them of the 2 factors were associated with clinical efficacy in the multivariate regression analysis. sIgE/sIgG4 decreased in AIT patients, while there was no change in total IgE.

The levels of serum sIgE and sIgG4 during AIT showed a time-dependent pattern. IgE-BF and IgE-FAB should be further investigated as biomarkers for predicting and monitoring AIT efficacy.

Allergen-specific immunotherapy (AIT) is the only means of altering the natural immunological course of allergic diseases and achieving long-term remission. Pharmacological measures are able to suppress the immune response and/or ameliorate the symptoms but there is a risk of relapse soon after these measures are withdrawn. Current AIT approaches depend on the administration of intact allergens, often comprising crude extracts of the allergen. We propose that the challenges arising from current approaches, including the risk of serious side-effects, burdensome duration of treatment, poor compliance and high cost, are overcome by application of peptides based on CD4+ T cell epitopes rather than whole allergens. Here we describe evolving approaches, summarize clinical trials involving peptide AIT in allergic rhinitis and asthma, discuss the putative mechanisms involved in their action, address gaps in evidence and propose future directions for research and clinical development.

Lipid transfer proteins (LTPs) syndrome is an important cause of multiple plant food allergy in the Mediterranean area. The effectiveness of sublingual immunotherapy (SLIT) with the LTP Pru p 3 extract has been little investigated in the real-world setting. This study aimed to investigate the outcome of Pru p 3 SLIT in real-life patients with LTP syndrome with/without concurrent reactions to peanut and/or nuts.

This was a prospective real-life study including all patients diagnosed with LTP allergy and treated with Pru p 3 SLIT between 2011 and 2018 in a tertiary hospital in Spain. Patients underwent open oral food challenge (OFC) tests for unpeeled peach and nuts/peanuts 1 year after the treatment started to assess food tolerance. A control group of patients diagnosed with LTP allergy who refused treatment with immunotherapy were included. Severity of symptoms and diet avoidance was recorded in both groups.

Twenty-nine patients with a median age of 24.7 years (range 5.5-43.1) were included: 100% were allergic to fruit; 72%, to peanut and/or nuts; 19 had a history of severe systemic reactions. Seven patients discontinued therapy; 3 (10%), due to adverse events. One year after SLIT start, 16 (73%) patients had negative OFC to peach; 95%, after 2 years; 69% had negative OFC to nuts/peanuts. The control group included 13 patients: 53.8% experienced reactions with new foods; severity of symptoms increased significantly (p < 0.001), and diet restrictions were maintained in this group.

SLIT with Pru p 3 shows a good safety profile, and avoid dietary restrictions in patients with LTP syndrome treated in the real-life setting.

The Global Initiative for Asthma Report updated in 2019 stated that potential benefits of allergen immunotherapy (AIT), compared to pharmacological and avoidance options, must be weighed against the risk of adverse effects and the inconvenience and cost of the prolonged course of therapy in asthma. Thus, with the aim of clarifying some aspects with regard to the possible use of AIT in allergic asthma treatment armamentarium, a group of expert allergists from the Spanish Allergy and Clinical Immunology Scientific Society (SEAIC), particularly from the Immunotherapy and Asthma Interest Groups developed a frequently asked questions in clinical practice. This document updates relevant topics on the use of AIT in asthma and could facilitate physician clinical decisions and improve health outcomes for individual patients.

We have previously reported that more than half of the patients who achieved desensitization after wheat rush oral immunotherapy (OIT) developed exercise-induced allergic reaction on desensitization (EIARD). However, data on EIARDs after slow OIT are lacking. Therefore, this study aimed to investigate the results of exercise provocation tests (EPTs) in patients after slow OIT for cow’s milk and wheat allergies.

This was a retrospective chart review of 87 EPTs in 74 patients. The EPTs were performed in patients who were desensitized to at least 6,600 mg cow’s milk protein or 5,200 mg wheat protein with slow OIT and were identified to be at a high risk of EIARDs. EPTs were performed after ingestion of the maximum desensitization dose. The patients’ clinical characteristics and symptoms were analyzed.

The EPT results were positive for cow’s milk in 49% (21/43) of the patients and for wheat in 48% (15/31) of the patients. There was no significant difference in the clinical characteristics between the EIARD-positive and EIARD-negative groups. The specific IgE (sIgE) levels before OIT and the reduction rates of sIgE before and after OIT did not correlate with the outcomes of the EPTs. Among the EIARD-positive patients, 13 patients (cow’s milk, n=7; wheat, n=6) underwent a second EPT, and the EIARD disappeared in 8 patients (cow’s milk, n=4; wheat, n=4).

EIARDs were observed after slow OIT for cow’s milk and wheat. Further research into the predictive factors of EIARDs in these patients is needed to understand its clinical manifestations.

While several systemic immunomodulatory effects of allergen-specific immunotherapy (AIT) have been discovered, local anti-inflammatory mechanisms in the respiratory tract are largely unknown. We sought to elucidate local and epithelial mechanisms underlying allergen-specific immunotherapy in a genome-wideapproach.

We induced sputum in hayfever patients and healthy controls during the pollen peak season and stratified patients by effective allergen-immunotherapy or as untreated. Sputum was directly processed after induction and subjected to whole transcriptome RNA microarray analysis. Nasal secretions were analyzed for Secretoglobin1A1(SCGB1A1) and IL-24 protein levels in an additional validation cohort at three defined time points during the three-year course of AIT. Subsequently, RNA was extracted and subjected to an array-based whole transcriptome analysis.

AIT inhibited pro-inflammatory CXCL8, IL24 and CCL26mRNA expression, while SCGB1A1, IL7, CCL5, CCL23 and WNT5BmRNAs were induced independently of the asthma status and allergen season. In our validation cohort, local increase of SCGB1A1 occurred concomitantly with the reduction of local IL-24 in upper airways during the course of AIT. Additionally, SCGB1A1 was identified as a suppressor of epithelial gene expression.

AIT induces a yet unknown local gene expression footprint in the lower airwaysthat on one hand appears to be a result of multiple regulatory pathways and on the other hand reveals SCGB1A1 as novel anti-inflammatory mediator of long-term allergen specific therapeutic intervention in the local environment.

Nanotechnology is science, engineering, and technology conducted at the nanoscale, which is about 1 to 100 nanometers. It has led to the development of nanomaterials, which behave very differently from materials with larger scales and can have a wide range of applications in biomedicine. The physical and chemical properties of materials of such small compounds depend mainly on the size, shape, composition, and functionalisation of the system. Nanoparticles, carbon nanotubes, liposomes, polymers, dendrimers, nanogels, among others, can be nanoengineeried for controlling all parameters, including their functionalisation with ligands, which provide the desired interaction with the immunological system, i.e. dendritic cell receptors to activate and/or modulate the response, as well as specific IgE, or effector cell receptors. However, undesired issues related to toxicity and hypersensitivity responses can also happen and would need evaluation. There are wide panels of accessible structures, and controlling their physico-chemical properties would permit obtaining safer and more efficient compounds for clinical applications goals, either in diagnosis or treatment.The application of dendrimericantigens, nanoallergens and nanoparticles in allergy diagnosis is very promising since it can improve sensitivity by increasing specific IgE binding, mimicking carrier proteins, or enhancing signal detection. Additionally, in the case of immunotherapy, glycodendrimers, liposomes, polymers, and nanoparticles have shown interest,behaving as platforms of allergenic structures, adjuvants or protectors of allergen from degradation or having a depot capacity.Taken together, the application of nanotechnology to allergy shows promising facts facing important goals related to the improvement of diagnosis as well as specific immunotherapy.

Subcutaneous allergen-specific immunotherapy (SCIT) is one of the main cornerstones in the treatment of allergic rhinitis in pediatric patients. It has demonstrated symptoms and quality of life improvement, but it is not exempt from adverse reactions (ADVrs). Nevertheless, there are a few reports that have evaluated their safety. Our objective was to evaluate the ADVr to SCIT in pediatric patients.

We reviewed 786 clinical records with SCIT from 2005 to 2018, comparing the clinical characteristics of patients with ADVrs with SCIT versus a group of a similar number of patients who completed SCIT (control group, CG). The analysis of ADVrs was according to the World Allergy Organization (WAO) 2010 grading system by frequency analysis, survival curve, and log rank.

Of 786 patients, 106 (13.4%) presented ADVrs, and the patients with ADVr had sensitivity and immunotherapy with at least 2 allergens versus CG p < 0.001, containing a combination of standardized and nonstandardized allergens (p = 0.003). The ADVrs were in the buildup phase (p < 0.001). The survival curve showed that 50% had some reaction at 12 weeks of SCIT. The most frequent ADVr was grade 1 in 73/106 patients (68.8%) and grade 2 in 33/106 (31.1%). The log-rank analysis between the grades of the WAO grading system showed a statistically significant difference (p = 0.02).

The SCIT is safe in pediatric patients. The ADVrs are infrequent, grade 1 being the most reported; however, at >12 weeks, the risk of ADVrs that involve 2 organs systems increases.