We previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT™) for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250μg) in a 12-month randomized controlled study (PEPITES) of peanut-allergic children aged 4-11 years.

To assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) open-label extension PEOPLE study.

Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250μg, subjects who had received DBV712 250μg in PEPITES underwent Month-36 double-blind, placebo-controlled, food challenge (DBPCFC) with an optional Month-38 sustained unresponsiveness (SU) assessment.

198 (93%) of 213 eligible subjects who had received DBV712 250μg in PEPITES entered PEOPLE, of whom 141 (71%) had assessable DBPCFC at Month 36. At Month 36, 51.8% (73/141) of subjects reached an eliciting dose (ED) of ≥1000 mg, compared with 40.4% (57/141) at Month 12. 75.9% (107/141) demonstrated increased ED compared to baseline. 13.5% (19/141) tolerated the full DBPCFC of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. 18 subjects underwent an optional SU assessment; 14/18 (77.8%) maintained an ED of ≥1000 mg at Month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events low (1%).

These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.

Peanut allergy is the leading cause of food-related anaphylaxis. Current management options can negatively affect food allergy-related quality of life. We aimed to investigate the efficacy of an investigational oral biologic drug (AR101).

The AR101 Trial in Europe Measuring Oral Immunotherapy Success in peanut-allergic children (ARTEMIS) trial was a multicentre, double-blind, randomised, placebo-controlled phase 3 trial done at 18 hospitals in Ireland, France, Germany, Italy, Spain, Sweden, and the UK. Children and adolescents with peanut allergy, aged 4-17 years, who developed dose-limiting symptoms to 300 mg or less peanut protein (equivalent to approximately one peanut kernel) during a double-blind placebo-controlled food challenge test at study entry were enrolled. Participants were randomly assigned (3:1) to receive daily doses of either AR101 oral immunotherapy (AR101 group) or a taste-masked placebo (placebo group). All participants, investigators, and care providers were masked to treatment allocation until the study was completed. Doses were increased every 2 weeks over 6 months until a dose of 300 mg was reached and maintained for 3 months. The primary endpoint was the proportion of participants in the intention-to-treat or safety population (defined as those participants who had been randomly assigned and had received at least one dose of the assigned drug) who could consume a single dose of 1000 mg (cumulative dose 2043 mg) peanut protein without developing dose-limiting allergic symptoms at an exit double-blind placebo-controlled food challenge after 9 months of treatment. Additional endpoints included safety (ie, the frequency and severity of adverse events) and changes in food allergy-related quality of life, assessed by use of age-appropriate Food Allergy Quality of Life Questionnaires (FAQLQs) and the Food Allergy Independent Measure (FAIM). The study is registered with ClinicalTrials.gov, NCT03201003 , and is completed.

Between June 12, 2017, and Feb 15, 2018, 227 patients were screened, of whom 175 were randomly assigned to the AR101 group (n=132) and the placebo group (n=43). All primary and secondary endpoints were met. 77 (58%) of 132 participants in the AR101 group tolerated 1000 mg peanut protein at the exit food challenge versus one (2%) of 43 participants in the placebo group (AR101-placebo treatment difference 56·0% [95% CI 44·1-65·2], p<0·0001). Adverse events were reported by almost all participants. The maximum severity of adverse events reported was mild or moderate for most participants who received AR101 (mild, 66 [50%] of 132 participants; moderate, 63 [48%]; and severe, one [1%]) or placebo (mild, 24 [56%] of 43 participants; moderate, 18 [42%]; severe, none). Participants aged 8-12 years in the AR101 group reported improvements that exceeded the minimum clinically important difference between the two groups across all FAQLQ domains. Additionally, participants in the AR101 group and their caregivers reported improvements that exceeded the minimum clinically important difference in FAIM domains related to the perceived likelihood and outcomes of a severe allergic reaction.

AR101 oral immunotherapy treatment led to rapid desensitisation to peanut protein, with a predictable safety profile that improved with treatment, and an associated improvement in self-reported and caregiver-reported food allergy-related quality of life. These patient-oriented outcomes provide invaluable data to help physicians, patients, and caregivers make informed, shared decisions on the management of peanut allergy.

Allergic rhinoconjunctivitis is a global health problem. Different Allergen ImmunoTherapy (AIT) regimes are marketed but have low adherence because they are expensive, complex and time consuming. New AIT forms are needed.

In a three-year follow-up double-blinded randomized placebo-controlled trial we aimed to investigate effect of intralymphatic AIT (ILIT).

Patients with grass pollen rhinoconjunctivitis were treated with either three ILIT injections and an ILIT booster one year later, three ILIT injection and a placebo booster or three placebo injections and a placebo booster. Primary outcome was improvement in a combined symptom and medication score, cSMS. A novel evaluation tool with a linear regression model of cSMS and grass pollen counts was developed. Secondary outcomes were changes in grass specific immunoglobulins and skin and nasal provocation tests to grass pollen.

36 patients were included. Log10 transformed cSMS was reduced by 0.30 (95%CI 0.11 – 0.49), p=0.002 equalling 48.5% (95%CI 24.5% – 62%), in the entirethree-year follow-up period, significant only in the first follow-up season but not in the second and third season. The regression model showed a 37%, p<0.001, reduction in cSMS. The booster injection had no additional. Secondary, repeated measures of IgE and IgG4 to grass, showed significant between-group difference and within-group change in the ILIT groups. No change in provocation test was found.

Intralymphatic immune therapy gives a substantial reduction in grass pollen allergy symptoms and use of rescue medication, significant in the first season after treatment. A booster injection had no additional effect.

Oral immunotherapy is a common treatment in cow’s milk protein allergy. The Department of Pediatric Allergology at the Children’s Hospital of Zaragoza performed a retrospective analysis of 335 infants under 1 year of age diagnosed with IgE-mediated cow’s milk and early treated. Clinical evaluation, skin prick test, and serum-specific IgE level control were performed before starting and after finishing treatment. Upon completion of treatment, more than 98% of patients became tolerant to milk and no one presented serious adverse reactions. Nowadays, the remaining non-tolerant patients (1.8%) can take milk or derivatives daily-as prophylaxis-to a certain maximum dose and still remain asymptomatic. After immunotherapy, both positive skin prick tests and a progressive decrease in specific IgE levels were found, as desensitization to milk increased. Conclusion: Oral immunotherapy is a safe and effective treatment against allergy to cow’s milk proteins in infants. Such treatment should be offered to the children’s families from the first moment of diagnosis. What is known: • Cow’s milk proteins are responsible for the earliest IgE-mediated allergic reactions in children. • Oral immunotherapy (OIT) is commonly used as cow’s milk allergy treatment and it is proposed at different ages. What is new: • OIT it is an effective and safe method with no severe reactions at early ages. • The number of reaching successful treatments is awesome so we believe that immunity response can be molded at the first months of life, so the probability of success with infants is greater than in older children.

Allergic diseases have remarkably increased in recent years. Nowadays, efforts for curing and management of these disorders are an important concern worldwide. Allergen-specific immunotherapy (ASIT) has recently gained more attention as a means for the management of allergic diseases. Adjuvants or helper agents are materials applied for better stimulating and shifting of protective responses, and these belong to an extremely diverse collection of complexes. The main function of adjuvants includes acting as depot foundations, transferring vehicles, and immunostimulators. Immunostimulatory adjuvants have gained increasing attention for ASIT. In this regard, the present study provides a review of old and new adjuvants used in allergen immunotherapy.

Immunotoxins appear as promising therapeutic molecules, alternative to allergen-specific-immunotherapy. In this work, we achieved the development of a protein chimera able to promote specific cell death on effector cells involved in the allergic reaction. Der p 1 allergen was chosen as cell-targeting domain and the powerful ribotoxin α-sarcin as the toxic moiety. The resultant construction, named proDerp1αS, was produced and purified from the yeast Pichia pastoris. Der p 1-protease activity and α-sarcin ribonucleolytic action were effectively conserved in proDerp1αS. Immunotoxin impact was assayed by using effector cells sensitized with house dust mite-allergic sera. Cell degranulation and death, triggered by proDerp1αS, was exclusively observed on Der p 1 sera sensitized-humRBL-2H3 cells, but not when treated with non-allergic sera. Most notably, equivalent IgE-binding and degranulation were observed with both proDerp1αS construct and native Der p 1 when using purified basophils from sensitized patients. However, proDerp1αS did not cause any cytotoxic effect on these cells, apparently due to its lack of internalization after their surface IgE-binding, showing the complex in vivo panorama governing allergic reactions. In conclusion, herein we present proDerp1αS as a proof of concept for a potential and alternative new designs of therapeutic tools for allergies. Development of new, and more specific, second-generation of immunotoxins following proDerp1αS, is further discussed.

Food allergy is an important medical problem with increasing prevalence throughout the world. Different approaches of food immunotherapy are being investigated including oral, epicutaneous and sublingual routes. Sublingual immunotherapy (SLIT) for food allergy involves placement of glycerinated allergen under the tongue daily to achieve allergen-specific desensitization. SLIT has been studied in the treatment of hazelnut, peach, apple, milk and peanut allergies with substantial focus on the treatment of peanut allergy. Phase II studies have shown SLIT for treatment of peanut allergy increases the tolerated dose of peanut by a substantial margin with fewer and less severe side effects than other modalities. This review discusses the mechanisms of SLIT, early studies of its use in food allergy and larger randomized controlled trials for treatment of peanut allergy. Future directions using the mechanisms involved in SLIT include oral mucosal immunotherapy for peanut allergy.

The effect of prolonged allergen immunotherapy is still insufficiently known, especially in elderly patients.

The effect after a 3-year course of injected allergen-specific immunotherapy (AIT) for grass pollen allergy in elderly patients with allergic rhinitis was observed.

Thirty-eight elderly patients (mean ± standard deviation, 66.2 ± 2.7 years old) who received preseasonal injected AIT or placebo for grass pollen allergy were monitored for 3 years and compared with a placebo group. The combined symptom medication score (CSMS), serum level of immunoglobulin G4 (IgG4) to phleum pratense 5 (Phl p5) and quality of life were assessed immediately after AIT and 3 years later.

After AIT, the CSMS was significantly decreased from 2.15 (range, 1.27-3.00) to 1.13 (range, 0.79-1.36) (p = 0.03) and remained lower (1.41 ± 0.72 versus 2.41 ± 1.11) than that in the placebo group during the 3 years after AIT. Serum-specific IgG4 against increased during the course of AIT and remained at a high level during further observation. Quality of life, based on the Rhinoconjunctivitis Quality of Life Questionnaire, was significantly decreased in the patients who received AIT from 1.51 (95% confidence interval [CI], 1.21-1.84) to 1.01 (95% CI, 0.93-1.87) (p < 0.05) and was decreased to 0.97-1.26 (95% CI, 0.88-1.82) during the 3 years after discontinuation of AIT.

A prolonged positive effect after AIT for grass pollen allergy was observed in elderly patients with allergic rhinitis. Further trials are needed to confirm this effect.Clinical trial MC56871/12.

Hypersensitivity or an allergy to chicken egg proteins is a predominant symptomatic condition affecting 1 in 20 children in Australia; however, an effective form of therapy has not yet been found. This occurs as the immune system of the allergic individual overreacts when in contact with egg allergens (egg proteins), triggering a complex immune response. The subsequent instantaneous inflammatory immune response is characterized by the excessive production of immunoglobulin E (IgE) antibody against the allergen, T-cell mediators and inflammation. Current allergen-specific approaches to egg allergy diagnosis and treatment lack consistency and therefore pose safety concerns among anaphylactic patients. Immunotherapy has thus far been found to be the most efficient way to treat and relieve symptoms, this includes oral immunotherapy (OIT) and sublingual immunotherapy (SLIT). A major limitation in immunotherapy, however, is the difficulty in preparing effective and safe extracts from natural allergen sources. Advances in molecular techniques allow for the production of safe and standardized recombinant and hypoallergenic egg variants by targeting the IgE-binding epitopes responsible for clinical allergic symptoms. Site-directed mutagenesis can be performed to create such safe hypoallergens for their potential use in future methods of immunotherapy, providing a feasible standardized therapeutic approach to target egg allergies safely.

Digital health technologies carry the great potential of assisting physicians in making well-informed diagnostic and therapeutic decisions. In allergy care, electronic clinical diaries have been recently used to prospectively collect patient data and improve diagnostic precision.

This review summarizes the clinical and scientific experience we gathered over 10 years of using a digital platform for patients suffering from seasonal allergic rhinitis.

The mobile application and back-office of AllergyMonitor (TPS software production, Rome, Italy) enable patients to record their daily allergy symptoms as well as drug and immunotherapy intake plus possible side effects in a customizable way. The results can be accessed by the patient and attending physician as concise reports via a smartphone or computer. This technology has been used in several clinical studies and routine practice since 2009.

Our studies showed that A) the etiological diagnosis of SAR may be supported by matching prospectively registered symptoms with pollen counts; B) it is possible to perform a short-term prediction of SAR-symptoms at individual level; C) the adherence to daily symptom monitoring can remain high (> 80%) throughout several weeks when prescribed and thoroughly explained by the treating doctor; D) the use of mobile technology can improve adherence to symptomatic drugs as well as allergen-specific immunotherapy and E) the choice of the correct symptom-severity-score is critical at patient level, but not at group level.

The studies and clinical practice based on the use of AllergyMonitor have proven the reliability and positive impact of a digital platform including an electronic diary (eDiary) on the diagnostic precision of SAR in poly-sensitized patients as well as patient adherence to both, drug therapy and allergen immunotherapy.