Timothy grass sublingual immunotherapy (SLIT)-tablets are indicated for children with allergic rhinitis with or without conjunctivitis (AR/C).

To use pooled analyses to assess the short- and long-term tolerability and safety of timothy grass SLIT-tablet in children.

Data from 9 double-blinded, randomized European or North American trials that included children with AR/C treated up to 3 years with once-daily timothy grass SLIT-tablet or placebo were pooled.

In all, 1818 (SLIT-tablet=923; placebo=895) subjects were included in the analysis. The frequency of treatment-emergent adverse events (AEs) was 86% in the SLIT-tablet and 83% in the placebo groups and of treatment-related AEs (TRAEs) was 59% and 23%, respectively. Most (98%) TRAEs were mild-to-moderate in severity. The two most common TRAEs with SLIT-tablet were oral pruritus (33%) and throat irritation (19%), which had a median onset of 1 day and recurrence of 14.5 and 5 days, respectively. In all, 8% of subjects in the SLIT-tablet and 2% in the placebo groups discontinued due to AEs. There were 7 serious AEs assessed as related to SLIT-tablet, 1 systemic allergic reaction (severe with a drop in blood pressure), 3 epinephrine administrations, no eosinophilic esophagitis events, and no serious airway obstructions. The safety profile was similar in subjects across geographic regions and with and without asthma.

Pooled data indicate that short- and long-term timothy grass SLIT-tablet is well tolerated in children, regardless of geographic region. AEs were generally local, mild, and transient allergic reactions.

The effect of oral immunotherapy (OIT) on wheat allergy is promising in terms of the potential to obtain desensitization; however, the frequency of exercise-induced allergic reactions on desensitization (EIARDs) and the associated risk factors remain to be determined.

Twenty-five patients underwent rush OIT for wheat allergy, and 21 achieved the full-dose intake of wheat products (5 g of wheat protein). Exercise-provocation tests were repeatedly performed after the ingestion of a full-dose wheat product. The time-course of the levels of the specific IgEs (sIgE) to wheat extract, total gliadin, deamidated gliadin, recombinant gliadin components (α/β-,γ-,ω1,2- and ω-5-) and glutenin (high and low molecular weight) components were analyzed using ImmunoCAP® , ELISA or IgE immunoblotting.

Fourteen patients (66.7%) were diagnosed as EIARD+, which remained 5 years after rush OIT in 11 patients (52.4%). There were no differences in the clinical backgrounds of the EIARD+ and EIARD- patients. However, EIARD+ patients showed significantly higher sIgE levels to all gliadin and glutenin components than EIARD- patients before OIT. The sIgE levels to each component decreased equally after 1 and 2 years of OIT. On IgE immunoblotting, sera from all patients reacted to the multiple gluten bands, and some reacted to the water-soluble bands. The intensity of all IgE-reactive bands also became equally lighter after OIT.

EIARDs were frequently observed and remained for a long period after successful OIT for wheat allergy. None of the specific wheat components were found to contribute to EIARDs.

Peanut allergy is a potentially severe and lifelong allergy, with few effective treatments or preventative measures.

To convene an expert panel of allergists, pediatricians, and advocates to discuss and highlight unmet needs in the prevention and management of peanut allergies.

Literature searches of PubMed were performed. The panel evaluated published data on the prevention of peanut allergy, treatment of existing peanut allergy, and management of reactions following unintentional peanut exposures.

Key unmet needs in the prevention and management of peanut allergy were identified, including: 1) enhancing and optimizing implementation of early peanut introduction as a means of preventing the development of peanut allergy; 2) developing knowledge translation strategies regarding the safety and efficacy data for current and emerging immunotherapies for peanut-allergic children to support their use in clinical practice; and 3) promoting understanding of true exposure risk in allergic individuals and ensuring access to epinephrine for accidental exposures that provoke severe reactions. Clinicians should help educate caregivers about the actual risks associated with peanut allergy, and its prevention and management so that treatment decisions can be evidence based rather than fear based. Support tools are needed to help address caregiver goals, expectations, and psychological barriers, as well as identify facilitators for prevention and treatment strategies.

There are significant unmet needs in our understanding of peanut allergy; addressing these needs will help to enhance understanding of how to most effectively prevent and treat peanut allergy, as well as educate the food-allergic and nonallergic community regarding current evidence-based practices.

The introduction of high-quality and standardized extracts for immunotherapy has renewed the interest in the treatment of pediatric allergic asthma that represents a high-prevalence disease.

In addition to clinical trials, several systematic reviews and metaanalyses were published, confirming overall the clinical efficacy of allergen immunotherapy in pediatric asthma. In addition, new data on the preventive effect of the treatment on asthma onset were published. Despite this, many intriguing questions emerged, in parallel to the development of knowledge.

Allergen immunotherapy is overall effective for the treatment of asthma in children, but a class-effect should not be claimed, rather the efficacy of each single product. According to the recent findings, the challenge for the future research will be to clarify: when to start immunotherapy in children, which are (if they exist) the predictive biomarkers for efficacy in the single individual, the magnitude of the preventive effect and the optimal duration of the treatment.

Sublingual immunotherapy (SLIT) is administered via tablets (SLIT-T) or liquid drops (SLIT-D). In North America, currently four SLIT-T formulations are FDA approved for allergy immunotherapy and SLIT-D are an off-label use of subcutaneous immunotherapy (SCIT) extracts. The purpose of this review is to compare and contrast aspects of SLIT-T and SLIT-D including physical characteristics, mechanism of action, dosing, efficacy, safety, adherence, and cost.

PubMed literature review (no limits), product prescribing information, and manufacturer websites.

Publications related to physical characteristics, mechanism of action, dosing, efficacy, safety, and adherence.

Published evidence indicates that tablet and drop formulations differ in regard to physical characteristics, dosing, and strength of evidence for efficacy. It is currently unknown if there are any differences in absorption and mechanism of action between the two formulations. Optimal dosing, efficacy, and safety have been established for SLIT-T. In contrast, in North America there is little support for efficacy of SLIT-D from randomized DBPC trials and dose ranges have not been appropriately evaluated. SLIT-T treat a single allergen whereas in the United States SLIT-D often contain multiple allergens to treat polysensitization. The safety profile of SLIT-T and SLIT-D appears similar, and both formulations are considered safer than SCIT.

Professional guidelines should make a clear distinction between SLIT-T and SLIT-D in their recommendations to minimize confusion with the umbrella term of SLIT.

While peanut oral immunotherapy (POIT) represents a promising treatment for peanut allergies in children, safety concerns remain a common barrier to widespread adoption. We aimed to systematically assess available evidence to determine the risk and frequency of adverse events occurring during POIT, and examine study-level characteristics associated with their occurrence and severity. A systematic search of MEDLINE, EMBASE, and Web of Science was conducted through April 2019. Controlled and non-controlled studies evaluating POIT were eligible. Twenty-seven studies, involving 1488 subjects, were included. Adverse events to POIT were common and led to treatment discontinuation in 6.6% of children (95% CI 4.4-9.0; 27 studies, I2 = 48.7%). Adverse events requiring treatment with epinephrine occurred among 7.6% (4.5-11.4; 26 studies, I2 = 75.5%) of participants, at a rate of 2.0 per 10,000 doses (0.8-3.7; 15 studies, I2 = 64.4). Use of a rush treatment phase and targeting a higher maintenance dose were associated with a higher risk and frequency of epinephrine use, while using co-treatments in addition to POIT was associated with a lower risk of treatment discontinuation due to adverse events. While adverse events to POIT are common, this study provides promising explorative evidence that certain modifications to existing treatment protocols could significantly improve treatment outcomes.

The prevalence of food allergy is increasing. At the current time, there are no approved treatments for food allergy. Major limitations of immunotherapy are long treatment periods (months or years), frequent clinic visits, high costs, increased risk of adverse events during treatment, and lack of durability of desensitization. Additionally, it is allergen-specific, and in those allergic to multiple allergens, the length and cost of treatment are further increased. In this review, we summarize recent developments in novel non-allergen-specific treatments for food allergy.

A number of monoclonal antibodies that block IgE or specific pro-allergenic cytokines or their receptors have shown promise in clinical trials for food allergy. The insight we have gained through the use of one drug for the treatment of an atopic disease is quickly being translated to other atopic diseases, including food allergy. The future for food allergy treatment with biologics looks bright.

There have been very few studies in real-life settings comparing the treatment effects of allergen immunotherapy (AIT) and pharmacotherapy for perennial allergic rhinitis (AR).

This study was performed to compare AIT and pharmacotherapy in terms of their effects on the symptom control and quality of life (QOL) of AR patients with/without asthma.

A total of 250 patients diagnosed with AR with/without asthma were included and assigned to the immunotherapy (AIT plus pharmacological treatment) or control (pharmacological treatment only) group. Clinical and medication scores, QOL scores, and lung function (forced expiratory volume in one second as a percentage; FEV1%) were measured at baseline and 3 years after the start of treatment.

This study showed that there was clinical improvement in AR symptoms in the AIT group, whereas standard pharmacotherapy alone had no significant effect on nasal symptoms. The QOL and satisfaction scores, as evaluated with a visual analogue scale (VAS), were further improved compared to the pharmacotherapy group. There was a significant improvement in medication scores in both AIT groups. According to our results, while total asthma scores and asthma control test scores were significantly improved in the HDM AIT group, they did not change in the Parietaria pollen AIT group. In our study FEV1% was increased compared to the baseline value in the AIT group, but it was not statistically significant. On the other hand, FEV1% remained without any improvement in patients on standard pharmacotherapy.

Perennial AIT was found to be superior to pharmacotherapy in decreasing symptoms as well as in improving QOL scores in AR patients with/without asthma. HDM AIT was more effective for asthma symptoms than Parietaria pollen AIT.

Allergy immunotherapy (AIT), both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), is an effective and safe treatment for allergic rhinitis and allergic asthma due to inhalant allergens. However, there are many variables in how it is administered.

To review the evidence that suggests the optimal practice(s) to minimize adverse reactions to AIT.

Articles that reported the results of various approaches to the practice of AIT and evidence-based guidelines were consulted for guidance about approaches that would minimize adverse reactions to AIT.

Evidence is presented that supports care in the preparation of allergy extracts for treatment; use of modified extracts; location for administration of SCIT and SLIT; risk factors for systemic reactions; AIT in patients on adrenergic blocking agents and angiotensin-converting enzyme inhibitors; use of premedication; the need for prescription of epinephrine autoinjectors; adjustments in dose for pollen seasons, interruptions in treatment, and for local and systemic reactions; and the safety in patients with autoimmune diseases and during pregnancy.

Although some of these variables have not been adequately studied, there are many studies that indicate practices that minimize the risk of adverse reactions for both SCIT and SLIT.

Most birch-pollen-allergic patients develop allergic cross-reactions to the major allergen found in apples Mal d1, known as pollen-related food allergy (prFA). This is due to a strong clinically relevant homology between the major allergen in birch Bet v 1 and Mal d 1. Daily apple consumption induces oral tolerance in prFA, but its effect on the inhalational allergy has not been investigated.

As continuous apple consumption might also mitigate the inhalational allergy, this study aimed to uncover apple cultivars suitable for treatment of birch-pollen rhinoconjunctivitis and apple allergy in a controlled and established dosage.

Patients (n=52) with birch-pollen allergy and prFA to apples were subjected to a Prick to Prick-Test (SPT) with 23 cultivars (red-fleshed-, old-traditional, and new-commercial). By SPT the apple parts flesh, peel-equatorial and peel-apical near the stalk were compared for their reactivity. One apple cultivar of each allergenicity class (low, middle, high) was subsequently tested in an oral provocation test (OPT).

According to the SPTs we provide a ranking of all 23 cultivars. Red-fleshed apples displayed the lowest reactivity, followed by old- and new cultivars. Four cultivars showed disagreement from their allergenicity class: Santana and Pink Lady®, new cultivars that provoked only low to moderate. In contrast, White Rosemary and Goldparmäne, two old cultivars, induced strong reactions. Skin reactivity increased from flesh to peel to stalk and SPT results could predict the severity of prFA of each allergenicity class.

Herein we propose a treatment protocol for allergen immunotherapy to birch-pollen and prFA with daily apple consumption. Red-fleshed-, old- and the new cultivars Santana and Pink Lady® provoke less allergic reactions and are suitable for initial induction. After a controlled and well tolerated increase of intake, also moderate and finally high allergenic apple cultivars should be integrated into treatment of birch-pollen allergenic patients.