Oral immunotherapy (OIT) can lead to desensitization to food allergens, but patients can experience treatment-related symptoms of allergic reactions that cause anxiety and treatment dropout. Interventions to improve OIT for patients are needed.

To determine whether fostering the mindset that non-life-threatening symptoms during OIT can signal desensitization improves treatment experience and outcomes.

In a randomized, blinded, controlled phase II study, 50 children/adolescents (28% girls, aged 7-17, M=10.82, SD=3.01) completed sixmonth OIT for peanut allergies. Patients and their parent(s) had monthly clinic visits at the Sean N. Parker Center for Allergy & Asthma Research between 1/5/2017-8/3/2017. All families received identical symptom management training. In a 1:1 approach, 24 patients and their families were informed that non-life-threatening symptoms during OIT were unfortunate side effects of treatment, and 26 patients and their families were informed that non-life-threatening symptoms could signal desensitization. Families participated in activities to reinforce these symptom mindsets.

Compared to families informed that symptoms are side effects, families informed that symptoms can signal desensitization were less anxious (B=-0.46, 95% CI (-0.76 to -0.16), p=0.003), less likely to contact staff about symptoms (5/24[9.4%] vs. 27/154[17.5%] instances, p=0.036), experienced fewer non-life-threatening symptoms as doses increased (BInteraction=-0.54(-0.83 to -0.27), p<0.001), less likely to skip/reduce doses (1/26[4%] vs. 5/24[21%] patients, p=0.065), and showed greater increase in patient peanut-specific blood IgG4 levels (BInteraction=0.76(0.36 to 1.17), p<0.001).

Fostering the mindset that symptoms can signal desensitization improves OIT experience and outcomes. Changing how providers inform patients about non-life-threatening symptoms is a promising avenue for improving treatment.

Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensensitivity disease. It is based on the production of IgE antibodies and T cell responses against per se innocuous antigens (i.e., allergens) and subsequent allergen-induced inflammation in genetically predisposed individuals. While allergen exposure in sensitized subjects mainly boosts IgE production and T cell activation, successful allergenspecific immunotherapy (AIT) induces the production of allergen-specific IgG antibodies and reduces T cell activity. Under both circumstances, the resulting allergen-antibody complexes play a major role in modulating secondary allergen-specific immune responses: Allergen-IgE complexes induce mast cell and basophil activation and perpetuate allergen-specific T cell responses via presentation of allergen by allergen presenting cells to T cells, a process called IgE-facilitated antigen presentation (FAP). In addition, they may induce activation of IgE memory B cells. Allergen-induced production of specific IgGs usually exerts ameliorating effects but under certain circumstances may also contribute to exacerbation. Allergen-specific IgG antibodies induced by AIT which compete with IgE for allergen binding (i.e., blocking IgG) inhibit formation of IgE-allergen complexes and reduce activation of effector cells, B cells and indirectly T cells as FAP is prevented. Experimental data provide evidence that by binding of allergen-specific IgG to epitopes different from those recognized by IgE, allergen-specific IgG may enhance IgE-mediated activation of mast cells, basophils and allergen-specific IgE+ B cells. In this review we provide an overview about the role of allergen-specific antibodies in regulating secondary allergen-specific immune responses.

(The SQ tree sublingual immunotherapy SLIT)-tablet (ALK-Abelló, Hørsholm, Denmark) is developed for treatment of tree polleninduced allergic rhinoconjunctivitis (ARC).

The aim of this pivotal phase III trial was to demonstrate the efficacy and safety of the SQ tree SLIT-tablet.

This was a randomized, double-blind, placebo-controlled trial with 634 subjects (12-65 years) with moderate-to-severe ARC despite use of symptom-relieving medication. Eligible subjects were randomized 1:1 to active or placebo treatment. The primary end point was the average daily ARC total combined score (TCS) during the birch pollen season (BPS) analyzed for subjects with diary data during the BPS. Secondary end points included average daily symptom scores (DSS) during the BPS, average TCS and DSS during the tree pollen season (TPS), and average daily medication scores (DMS) in the BPS and TPS.

The primary and key secondary end points demonstrated statistically significant and clinically relevant effects of the SQ tree SLIT-tablet compared with placebo. For the BPS, absolute (relative) differences from placebo were 3.02 (40%) for TCS, 1.32 (37%) for DSS, and 1.58 (49%) for DMS (all P < .0001). For the TPS, absolute (relative) differences from placebo were 2.27 (37%) for TCS, 0.99 (33%) for DSS, and 1.20 (47%) for DMS (all P < .0001). Treatment was well tolerated. The most frequently reported treatment-related adverse events were mild or moderate local reactions related to sublingual administration.

The trial demonstrated the efficacy and safety of the SQ tree SLIT-tablet compared with placebo during the BPS and TPS in adolescents and adults with birch pollen-induced ARC (EudraCT 2015-004821-15).

The safety and efficacy of long-term milk oral immunotherapy (OIT) in Finnish children with persistent cow’s milk allergy(CMA) was evaluated in an open-label, non-randomized study.

During the 11-year study, 296 children aged 5 years or older with immunoglobulin E (IgE)-mediated CMA started milk OIT. Follow-up data was collected at three timepoints: the post build-up phase, one year thereafter, and at the cross-sectional long-term follow-up between January 2016 and December 2017. Patients were divided according to baseline milk specific IgE (sIgE) level and by the amount of milk consumption at the long-term follow-up. The high dose group consumed ≥ 2 dl of milk daily, while the failure group consumed < 2 dl of milk or were on a milk-avoidance.

Out of the initial study group, 244/296 (83%) patients participated in the long-term follow-up. Among these patients, 136/244 (56%) consumed ≥ 2 dl of milk daily. The median follow-up time was 6.5 years. Of the recorded markers and clinical factors, the baseline milk sIgE level was most associated with maintaining milk OIT (P < .001). Respiratory symptoms in the post build-up phase increased the risk of treatment failure (OR 3.5, 95% CI: 1.5-8.1, P = .003) and anaphylaxis (OR 14.3, 95% CI: 1.8-114, P = .01).

More than half of the patients were able to maintain the targeted milk dose in their daily diet. Baseline milk sIgE level and reactivity during the early treatment stage strongly predicted the long-term outcome and safety of milk OIT.

Data comparing the long-term efficacy and safety of subcutaneous immunotherapy (SCIT) using house dust mite (HDM) in children and adults with allergic rhinitis (AR) are limited. This study aimed to compare the long-term effects of HDM-SCIT in a cohort of Chinese pediatric and adult patients with AR.

A total of 124 pediatric and adult AR patients received HDM-SCIT for 3 years, with 118 patients being followed-up for 2 years. Prior to treatment (baseline), at the end of the 3-year treatment periods (third year) and 2 years after the discontinuation of treatment (fifth year), all patients were evaluated for total nasal symptom scores (TNSS), daily medication score (DMS), total combined score (TCS; symptoms [nasal + ocular] + DMS) and quality of life (QoL). Safety was assessed according to adverse events reported.

After 3-year treatment, HDM-SCIT significantly improved symptoms and QoL scores at the end of the third and fifth years in both groups. Better improvements were observed in the third and fifth years based on baseline, in children compared to adults (TNSSΔ3: 6.66 vs. 5.41, P = 0.011; TCSΔ3: 4.30 vs. 3.83, P = 0.027 and TNSSΔ5: 6.16 vs. 4.86, P = 0.037; TCSΔ5: 4.11 vs. 3.62, P = 0.044).Shorter duration of AR history before SCIT (<10 vs. ≥10 years) resulted in better improvements at the end of the third and fifth years (TCSΔ3: 4.12 vs. 3.13, P= 0.036; TCSΔ5: 3.90 vs. 3.09, P = 0.033). HDM-SCIT was safe and comparable in both children and adults with AR.

Children with AR may achieve better long-term efficacy of HDM-SCIT than adults with AR.

IgE-mediated food allergies are an increasing health concern, and current management includes food avoidance and use of emergency medications. Effective treatment of food allergy is highly desirable. Next generation approaches for the treatment of food allergy aim to improve both safety and efficacy, potentially including long-term tolerance.

Oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) will likely be integrated into clinical practice as part of food allergy management in the near future. Newer approaches, such as sublingual immunotherapy (SLIT), modified proteins, lysosomalassociated membrane protein DNA (LAMP DNA) vaccines, and the use of immunomodulatory agents, are early in development and depending on results, could also become important treatment options. This is a review of novel approaches to the treatment of food allergythat are currently under investigation, including the use of SLIT, modified proteins, probiotics, Chinese herbal supplements, biologic therapies, and DNA vaccines, as well as a summary of the current status of OIT and EPIT.

Ultra-rush (UR) are induction protocols used in venom immunotherapy (VIT).

To evaluate the adverse reactions during a 210-minutes UR and determine possible risk factors.

Retrospective study of 129 patients submitted to UR with VIT in the last 20 years.

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.

Most SR during UR were mild with no need for adrenaline treatment. The honey bee venom and the severity of the anaphylaxis during the field sting were the only SR´s risk factorsfor systemic adverse reactions during the UR.