Randomized controlled trials (RCTs) are the gold-standard for benefit-risk assessments during drug approval processes. Real-word data (RWD) and the resulting real-world evidence (RWE) are becoming increasingly important for assessing the effectiveness of drug products after marketing authorization showing how RCT results are transferred into real life care. The effectiveness of allergen immunotherapy (AIT) has been assessed in several RWE studies based on large prescription databases. We performed a literature search for retrospective cohort assessments of prescription databases in Europe to provide an overview on the methodology, long-term effectiveness outcomes, and adherence to AIT. Thirteen respective publications were selected. AIT was more effective in reducing the progression of allergic rhinitis (AR) compared to a non-AIT control group receiving only symptomatic treatment for AR for up to 6 years. The development and progression of asthma were hampered for most endpoints in patients treated with most preparations compared to the non-AIT group, receiving only anti-asthmatic medication. The results for "time to onset" of asthma were inconsistent. Adherence to AIT decreased during the recommended 3-year treatment period, however, in most studies higher adherence to subcutaneous than to sublingual AIT was shown. The analysis of long-term effectiveness outcomes of the RWE studies based on prescription databases confirms the long-term efficacy of AIT demonstrated in RCTs. Progression of rhinitis and asthma symptoms as well as delayed onset of asthma triggered by different allergens, real life adherence to the treatment shows differences in particular application routes. 

Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.

House dust mite (HDM) sublingual immunotherapy (SLIT) tablets have been approved for the treatment of patients with allergic rhinitis (AR). However, the meta-analysis on the efficacy of HDM-SLIT tablets for HDM-induced AR patients remained limited.

Five databases were searched including: PubMed/MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and CINAHL for randomized controlled trials (RCTs) that addressed the efficacy and safety of HDM-SLIT tablets compared with placebo until January 2022. The primary outcome was a combined symptom and medication score (CSMS) after treatment.

Eight eligible RCTs were identified with a total of 3601 patients treated with HDM-SLIT tablets and 2783 patients who received a placebo. The CSMS was significantly lower in the HDM-SLIT tablet group compared with the placebo (standardized mean difference (SMD) -0.28 [95% CI: -0.32 to -0.23]). There was a significant reduction in rhinitis symptom scores, rhinitis medication scores, total combined conjunctivitis scores, and rhinoconjunctivitis quality of life questionnaire scores. The consistent efficacy compared to the placebo has been exhibited over the different kinds and doses of HDM tablets (6 SQ, 12 SQ, 300 IR, and 500 IR) and age groups (>5 years old, adolescents and adults) with low degrees of variability across the studies. There was no significant difference in proportions of participants who were injected with epinephrine between the treatment- and placebo groups.

HDM-SLIT tablet is an effective treatment in reducing rhinitis symptoms and medication use in AR patients with favorable safety. They also improve quality of life and conjunctivitis symptoms.

Local allergic rhinitis (LAR) is a clinical rhinitis phenotype characterized by the presence of nasal symptoms of AR in nonatopic patients with a negative skin prick test and undetectable specific IgE (sIgE) in serum against inhalant allergens but with a positive nasal allergen provocation test. This study evaluated the effectiveness of a 12-month course of sublingual immunotherapy (SLIT) for house dust mite (HDM) allergies in adult patients with confirmed LAR and concomitant asthma.

The study was a prospective, double-blind, placebo-controlled trial with patients diagnosed with LAR to HDMs and with concomitant asthma who underwent a 12-month treatment course of SLIT for HDM allergies. Seventeen patients were randomized to SLIT with the use of allergen extracts of D. pteronyssinus and D. farinae (50/50%) in SQ-HDM SLIT tablets and 15 patients were randomized to the placebo group. The total rhinitis score (TRSS), total asthma symptom score (TASS), combined total symptom score (TSS), total medication score (TMS), and FEV1 were analyzed.

In the final analysis, 16 patients who received SLIT and 14 who received placebo who completed the study protocol were included. Significant reductions in TRSS, TASS, TSS, and TMS after 12 months of treatment were observed in patients after SLIT (p < 0.05). A significant increase in the mean FEV1 between baseline and after 12 months of therapy was observed in the study, with p = 0.03 in the study group.

SLIT can improve nasal and bronchial symptoms and reduce symptomatic treatment in patients with LAR and asthma and with hyperresponsiveness to HDMs.

There are no diagnostic and/or prognostic markers of the treatment outcome in patients receiving allergen immunotherapy (AIT). Although numerous allergen epitopes are known, their value in this context has not been investigated. This paper deals with re-evaluation of sera from patients who underwent AIT against rBet v 1 for treatment of their soya allergy (BASALIT trial).

To evaluate the diagnostic and/or prognostic potential of allergen epitopes recognition by antibodies from patients with birch-related soya allergy before and after rBet v 1-immunotherapy.

PR-10 epitope-binding profiles from 34 patients were identified in silico using a statistical peptide phage display at start and at end of AIT. IgE- and IgG-binding to these peptide epitopes was measured in peptide microarrays. Clinical relevance of epitopes was evaluated by comparing these measurements to a number of treatment outcome measures recorded during double-blind placebo-controlled food challenge at start and end of AIT.

We showed that IgG- and IgE-recognition of peptide epitopes after AIT were surrogate markers of 5 out of 12 analysed treatment outcome measures using this patient cohort. Seven epitopes were identified from multiple PR-10 allergen sequences. Twenty-six peptide epitopes were used for IgG and IgE measurements. IgE-binding to one of the epitopes was associated with stronger intensity of oral tingling/itching after ingesting soya at start of AIT. IgG recognizing two other epitopes at start of AIT could predict decreased Cor a 1-specific IgE concentration (p = .043) and decreased lip swelling intensity (p = .016) after AIT. Tolerance to increasing amounts of soy at food challenge correlated with IgG-binding to another epitope at start of AIT (p = .046).

IgG- and IgE-binding to peptide epitopes in PR-10 is a potential indicator of the outcome and clinical course of AIT of soya-sensitized patients with rBet v 1.

While the historic management of food allergy includes avoidance strategies and allergic reaction treatment, oral immunotherapy (OIT) approaches have become more commonly integrated into therapeutic approaches. International guidelines, phase 3 trials and real-world experience have supported the implementation of this procedure. However, OIT is an elective, rarely curative procedure with inherent risks that necessitates an increased degree of health literacy for the patients and families. Families assume the responsibility of amateur healthcare providers to ensure the daily safe administration of the allergenic food. As such, it is incumbent upon physicians to ensure that families are prepared for this role. A thorough educational and shared decision-making approach is necessary during the counselling and consent process to adequately inform the families. Educated discussion about the efficacy and patient-centred effectiveness, therapeutic alternatives and family goals is required to align physician and patient expectations. A frank discussion about the struggles, practical challenges, risks and contraindications can help to develop an understanding of the risk mitigation strategies employed to maintain safety. Physicians should develop a proactive approach to educate families about this, at times, burdensome procedure. This educational approach should encourage ongoing support starting prior to consent through the maintenance visits. By preparing families for their unique management role, physicians can help ensure the safe and successful integration of OIT into the therapeutic offering for the management of food allergies.

This is a retrospective analysis of the clinical evolution of 14 patients diagnosed with allergic rhinoconjunctivitis (AR) and/or allergic asthma (AA) caused by Alternaria alternata, who were attended by the allergology service of Vega Baja Hospital of Orihuela (Alicante, Spain). The purpose was to assess the clinical impact and safety of 1-year of subcutaneous immunotherapy with a polymerized molecular allergoid of Alt a 1. Impact of the treatment on allergic diseases (mean number AR/AA episodes and ARIA/GINA classifications), changes in symptoms and prescribed medication, change in the global subjective clinical status of patients and satisfaction with the treatment were also evaluated. Adverse reactions were also recorded and analysed. After 1-year of treatment, fewer AR and AA episodes (p less than 0.05) and improvements in ARIA/GINA classifications were observed. Significant improvements of symptoms (p less than 0.05) and a resulting general reduction of the medication prescribed was also detected. Improvements in the global subjective clinical status and good satisfaction rates were observed. Only 1 patient presented a local and not clinically relevant adverse reaction. The treatment showed promising effects with a significant improvement in the clinical status of all patients with a good safety profile.

Subcutaneous immunotherapy (SCIT) is an effective treatment for pediatric allergic rhinitis (AR), but its efficacy fluctuates among individuals. This study aims to identify the profile of serum exosomes derived microRNAs (miRNAs) and evaluate their capacities to early predict SCIT efficacy in pediatric AR.

High-throughput sequencing was applied to identify the miRNA of serum exosomes in AR children. GO enrichment and KEGG pathway analysis were performed to enrich the biological annotations of target mRNAs of miRNAs. Then we validated differentially expressed miRNAs in two independent cohorts by RT-qPCR. Logistic regression and receiver operating characteristic curve (ROC) were applied to evaluate the abilities of identified miRNAs in predicting the efficacy of SCIT in AR children.

A total of 812 miRNAs were detected in the serum exosomes, including 16 upregulated and 14 downregulated. Differentially expressed genes are enriched in the biological process of developmental process and regulation of cellular process, and gathered in pathways such as the signaling pathways regulating pluripotency of stem cells and the Wnt signaling pathway. In the first validation cohort, hsa-miR-4669 (P=0.009) and hsa-miR-4686 (P=0.032) were significantly downregulated in the effective group than the ineffective group, while hsa-miR-3196 (P=0.015) was upregulated. In the second cohort, hsa-miR-4669 level (P<0.0001) was downregulated in the effective group than the ineffective group. In addition, logistic regression revealed that hsa-miR-4669 level was correlated with the visual analogue scale (r=0.323, P=0.001) and total nasal symptoms score (r=0.269, P =0.007). ROC curve highlighted that hsa-miR-4669 level exhibited a reliable accuracy in predicting SCIT efficacy in pediatric AR (AUC=0.785).

Serum exosomes derived miRNA were associated with the efficacy of SCIT. Serum exosomes derived hsa-miR-4669 might serve as a novel biomarker for early predicting the response of SCIT in AR children.

The purpose of this review is to provide an update on the intriguing relationships between allergies, allergen immunotherapy, cancer, and immune disorders. Allergic diseases and cancer are increasing in incidence and prevalence and a potential relationship, or not, between these diseases have been suggested for many years.

Recent findings suggest that there may be some causative effects between certain types of cancer and allergic diseases, as described in the text. Some types of cancer may be more linked to the presence of an allergic disease, than others. However, epigenetic factors, such as tobacco smoke alcohol and toxic substances should also be taken into consideration.

The association between allergy and cancer is complex and depends on the specific allergy and the specific organ under consideration. Regarding pancreatic cancer, colorectal cancer (CRC), and glioma, all types of allergies were shown to be a protective factor. Conversely, asthma is a risk factor for lung cancer as is atopic dermatitis for skin cancer. Despite extensive research, no definite relationship has been determined, and no clear relationship, either positive or negative, to allergies can be observed. These results should be corroborated with large epidemiological well designed prospective studies due to some weaknesses in the previous investigations.

In this work, we investigate the correlation between ragweed pollen concentration and conjunctival, nasal, and asthma symptom severity in patients allergic to ragweed pollen using ambient pollen exposure in the Milan area during the 2014 ragweed season We calculate the pollen/symptom thresholds and we assess the effectiveness of ragweed allergen immunotherapy (AIT). A total of 66 participants allergic to ragweed (Amb a 1) were enrolled in the study and divided into two groups: AIT treated (24) and no AIT treated (42). Pollen counts and daily symptom/medication patient diaries were kept. Autoregressive distributed lag models were used to develop predictive models of daily symptoms and evaluate the short-term effects of temporal variations in pollen concentration on the onset of symptoms. We found significant correlations between ragweed pollen load and the intensity of symptoms for all three symptom categories, both in no AIT treated (τ = 0.341, 0.352, and 0.721; and ρ = 0.48, 0.432, and 0.881; p-value < 0.001) and in AIT treated patients ([Formula: see text]= 0.46, 0.610, and 0.66; and ρ = 0.692, 0.805, and 0.824; p-value < 0.001). In both groups, we observed a positive correlation between the number of symptoms reported and drug use. Mean symptom levels were significantly higher in no AIT treated than in AIT treated patients (p-value < 0.001) for all symptom categories. Pollen concentration thresholds for the four symptom severity levels (low, medium-low, medium-high and high) were calculated. Ragweed pollen concentration is predictive of symptom severity in patients with a ragweed (Amb a 1) allergy. Patients treated with AIT had significantly reduced mean symptom levels compared to those without AIT.