The Agency for Healthcare Research and Quality and the National Institute of Allergy and Infectious Diseases organized a workshop to develop trial concepts that could improve the usage and effectiveness of aeroallergen immunotherapy (AAIT). Expert groups were formed to accomplish the following tasks: 1) Propose a study design to compare effectiveness and safety of subcutaneous versus sublingual AAIT; 2) Propose a study design to compare effectiveness and safety of AAIT using one or a few allergens vs all or most allergens to which a patient is sensitized; 3) Propose a study design to determine whether AAIT can alter the progression of childhood allergic airways disease; 4) Propose a study design to determine the optimal dose and duration of AAIT to achieve maximal effectiveness with acceptable safety. Study designs were presented by the workgroups, extensively discussed at the workshop and revised for this report. The proposed trials would be of long duration, and require large, highly characterized patient populations. Scientific caveats and feasibility matters are discussed. These concepts are intended to help the development of clinical trials that can address some of the major questions related to the practice of AAIT for the management and prevention of allergic airways disease.

There are currently no approved treatments for peanut allergy.

To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children.

Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n = 356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein.

Daily treatment with peanut patch containing either 250 μg of peanut protein (n = 238) or placebo (n = 118) for 12 months.

The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs).

Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% [95% CI, 12.4%-29.8%; P < .001]). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group.

Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-μg peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined.

IgE-mediated food allergy (FA) is a potentially life-threatening condition with a negative impact on quality of life and an increasing prevalence in westernized countries in the recent two decades. A strict avoidance of the triggering food(s) represents the current standard approach. However, an elimination diet may be difficult and frustrating, in particular for common foods, (e.g. milk, egg, and peanut). Food allergyimmunotherapy (FA-AIT) may provide an active treatment that enables to increase the amount of food that the patient can intake without reaction during treatment (i.e. desensitization), and reduces the risk of potential lifethreatening allergic reaction in the event of accidental ingestion. However, several gaps need still to be filled. A memorable Latin orator stated: “Est modus in rebus” (Horace, Sermones I, 1, 106-07). This sentence remembers that there is a measure in everything to a proper proportion of therapy. The common sense of measure should find application in each stage of treatment. A personalized approaching should consider the specific willing and features of each patient. Efforts are devoted to improve the efficacy, the safety but also the quality of life of patients suffering from FA. In the near future it will be important to clarify immunological pathways of FA-AIT, and to identify reliable biomarkers in order to recognize the most suitable candidates to FA-AIT and algorithms for treatments tailored on wellcharacterized subpopulations of patients.

Although regulatory authorities have recently recommended the use of a combined symptom-medication score as a primary efficacy end point, none has been psychometrically validated. Here, we sought to determine to what extent allergic rhinitis (AR)-related patientreported outcomes (symptom scores, medication scores, disease control scores, and satisfaction or quality-of-life scales) have been assessed for construct, content, and/or criterion validity, reliability, responsiveness, and the minimal clinically important difference. We searched the PubMed database from January 1997 to June 2018 with logical combinations of key words related to validation, AR, and patient-rated outcomes and scales. From a total of 1705 potentially relevant publications, 55 were reviewed. Despite the current emphasis on a combined symptom-medication score for evaluating the efficacy of allergen immunotherapy in AR, symptom scores have not been extensively validated, and we did not find any publications describing the validation of a medication score. Disease control scales (mainly the Rhinitis Control Assessment Test, the Control of Allergic Rhinitis and Asthma Test, and the Allergic Rhinitis Control Test) and health-related quality-of-life scales (mainly the Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ] and the mini-RQLQ) have been extensively validated in AR but have some practical disadvantages as primary efficacy criteria in clinical trials.

SCIT is highly effective but safety risks exist.

The aims of this study were to: 1) identify clinical practices that could influence fatal and non-fatal systemic allergic reactions (SRs) to SCIT; and 2) identify SCIT-associated infections.

From 2008-2016, 27-51% of AAAAI/ACAAI members completed an annual survey of SCIT-related SRs of varying severity. Post-injection local cutaneous and systemic infections were queried for 2014-2016. For 2014-2016, respondents were queried about timing of onset of SRs, post-injection waiting times, and prescription/use of epinephrine auto-injectors.

Data were gathered on 54.4 million injection visits (2008-2016). Two confirmed fatalities from SCIT occurred between 2008-2014. An additional five confirmed fatalities occurred between 2015-2017. No infections occurred in 17.3 million injection visits (2014-2016). Among practices monitoring patients for at least 30 minutes, 15% of SRs occurred after 30 minutes. Practices prescribing an epinephrine auto-injector >90% of the time (29% of practices) did not experience lower rates of delayed Grade 3/4 SRs. Of patients experiencing Grade 3/4 delayed SRs, 26% and 8% used prescribed self-injectable epinephrine devices during 2014-2015 and 2015-2016, respectively.

There is an unexplained slight increase in SCIT-related fatalities for 2015-2017, although mean annual reported events over 9 years (0.8 fatal reactions/year) have declined. SCIT-related infections were not identified during two years of surveillance. The 15% incidence of delayed-onset SRs (> 30 min) is similar to a prior annual survey. Prescribing epinephrine auto-injectors for SCIT does not appear to improve outcomes, possibly due to low rates of self-administration.

Food allergy is a growing health problem worldwide that impacts millions of individuals. Current treatment options are limited and strict dietary avoidance remains the standard of care. Immunotherapy using whole, native allergens is under active clinical investigation but harbors the risk of severe side effects including anaphylaxis. Newer food-specific therapies with hypoallergenic proteins may potentially offer safer treatment alternatives, and this review seeks to investigate the evidence supporting the use of these modalities.

The utilization of different methods to alter allergen structure and IgE binding leads to reduced allergenicity and decreases the risk for systemic reactions, making the use of potential therapies including extensively heated egg/milk, peptide immunotherapy, recombinant allergen immunotherapy, and DNA vaccines safe and possibly efficacious forms of treatment in food allergy. However, for the majority of these treatment modalities, limited data currently exists looking at the safety and efficacy in human subjects with food allergy. This review provides a comprehensive overview of the current evidence examining the safety and efficacy of hypoallergenic proteins in the treatment of food allergies.

This study focuses on side effects of cow’s milk oral immunotherapy (CM-OIT) using consensus definitions of food-induced anaphylaxis.

To evaluate the risk of allergic reactions (ARs) and to identify risk factors associated with higher risk of anaphylactic ARs (AARs) during CM-OIT in children.

Clinical charts of children receiving CM-OIT were carefully reviewed.ARs were defined as single-organ ARs and AARs were defined as involvement of 2 organ systems and/or hypotension in response to CM protein. Descriptive statistics were used to represent demographics, occurrence, reaction characteristics and co-morbidities. Poisson analysis was performed to evaluate risk factors associated with AARs.

In 114 (88.4%) patients the 101.1 μg maintenance dose was reached in 210 minutes. Systemic reactions (SR) occurred in 22% of patients (71% mild). There were no severe SR, late reactions or fatalities. Adrenaline was administered in 10% of all UR. The SR were more frequent with honey bee VIT and had greater severity in the patients with a previous severe systemic sting reaction. No significant difference in the risk of SR was found with other demographic, clinical or laboratory factors. There were 5% of large local reactions (LLR), these being more frequent in females.

Although the majority of ARs during OIT are non anaphylactic, AARs occur frequently. Children with higher sIgE for alpha-lactalbumine and casein at baseline seem to be at higher risk for AARs during OIT.

Allergen immunotherapy (AIT) treatment for allergic rhinitis and asthma is used by 2.6 million Americans annually. Clinical and sterility testing studies identify no risk of contamination or infection from extracts prepared using recommended aseptic techniques, but regulatory concerns persist. Social media can be used to investigate rare adverse effects not captured by traditional studies.

To investigate large social media databases for suggestion of AIT skin and soft tissue infection (SSTI) risk and compare this riskto a comparator procedure with a sterile pharmaceutical.

We analyzed USA-restricted data from over 10 common text-based social media platforms including Facebook, Twitter, and Reddit between 2012-2016. We employed natural language processing (NLP) to identify posts related to AIT and, separately, Influenza vaccination (comparator procedure). NLP was followed by manual review to identify posts suggesting a possible SSTI associated with either AIT or Influenza vaccination. SSTI frequencies with 95% confidence intervals (CI) were compared.

We identified 25,126 AIT posts, which were matched by social media platform to 25,126 Influenza vaccination-related posts. NLP identified 4,088 (16.3%) AIT posts that required manual review, with 6 posts (0.02%, 95%CI 0.005% to 0.043%) indicative of possible AITrelated SSTI. NLP identified 2,689 (10.7%) Influenza posts that required manual review, with 7 posts (0.03%, 95%CI 0.007% to 0.048%) indicative of possible Influenza vaccination-related SSTI.

Social media data suggest that SSTI from AIT and Influenza vaccination are equally rare events. Given that AIT’s SSTI riskappears comparable to the risk using a sterile pharmaceutical based on social media data, current aseptic technique procedures seem safe.

Allergen specific immunoglobulin can be present in the nasal mucosa of patients with non-allergic rhinitis (NAR). This condition is defined as local allergic rhinitis. However, the reported presence of nasal specific immunoglobulin E (nspIgE) among NAR is variable. The aim of this review was to summarize the studies which reported the presence of nspIgE among patients diagnosed as NAR.

Embase (1947- ) and Medline (1946-) were searched until 6th June 2017. A search strategy was utilized to identify studies on nspIgE among patients with NAR. The target population was patients with symptoms of rhinitis, but negative systemic allergen sensitization. Studies with original data on detectable nspIgE among the NAR population were included. Meta-analysis of single proportions as a weighted probability %(95%CI) was performed. Heterogeneity was explored amongst studies.

A search strategy returned 2286 studies and 21 were included. These studies involved 648 participants with NAR. NspIgE was detected using either; 1. nasal secretions, 2. epithelial mucosa sampling, 3. tissue biopsies or 4. In-situ tests. Metaanalysis was performed on studies with nasal secretions. The weighted proportion of detectable nspIgE in nasal secretions within patients with NAR was 10.2 (7.4- 13.4) %. Population definitions partly explained variability. Detection of nspIgE was lower in patients without a history suggestive of allergy compared to those with a positive allergic history (0 (0-3.1) % v 19.8 (14.5-25.6) %, p<0.01).

NAR with positive allergy history suggests presence of nspIgE. These patients warrant further allergology evaluation to confirm localized nasal allergy, as they benefit from allergy therapy such as immunotherapy.

Allergic rhinitis (AR) affects 23-30% of the European population with equal prevalence reported in Belgium. Despite guidelines on the correct use of effective treatment, up to 40% of AR patients remain uncontrolled. Allergen immunotherapy (AIT) has been shown to improve the level of control up to 84% of patients being controlled by AIT. Recently, new guidelines for AIT have been published, supporting the clinical evidence for effectiveness of various subcutaneous and sublingual products for AIT in patients who are allergic to airborne allergens. AIT in AR patients not only reduces nasal and/or ocular symptoms but also induces tolerance and has preventive potential. Adoption of AIT into daily clinical practice in Belgium and other European countries is hampered primarily by reimbursement issues of each of the single products but also by several patient- and physician-related factors. Patients need to be better informed about the effectiveness of AIT and the different routes of administration of AIT. Physicians dealing with AR patients should inform patients on tolerance-inducing effects of AIT and are in the need of a harmonized and practical guide that supports them in selecting eligible patients for AIT, in choosing evidence-based AIT products and in following treatment protocols with proven efficacy. Therefore, a stepwise and holistic approach is needed for better adoption of AIT in the real-life setting in Belgium.