CoFAR investigators previously reported 52-week outcomes from a randomized, controlled trial of peanut EPIT, observing modest and statistically significant induction of desensitization, highest in children ages 4-11 years.

To evaluate changes in efficacy, safety, and mechanistic parameters following extended open-label peanut EPIT.

Peanut-allergic participants (4-25 years) received 52 weeks of placebo (PLB), Viaskin Peanut 100 mcg (VP100) or 250 mcg (VP250), then crossover to VP250 for placebo (PLB-VP250) and VP100 (VP100-VP250) participants and continuation of treatment for VP250 participants (total=130 weeks of active EPIT). Efficacy was assessed by DBPCFC (5044 mg peanut protein) and adherence, safety and mechanistic parameters were evaluated.

At week 130, desensitization success was achieved in 1/20 (5%) PLB-VP250, 5/24 (20.8%) VP100-VP250, and 9/25 (36%) VP250 participants with median successfully consumed dose (SCD) change from baseline of 11.5 mg, 141.5 mg, and 400 mg, respectively. Median age (years) for week 130 desensitization success was 6.2 years (IQR:5.2,9.1) versus 9.4 years (IQR:7.6,12.8) for failures (p<0.001). Adherence was 96%. Adverse reactions were predominantly local patch-site reactions. Significant increases in peanut- and Ara h2-specific IgG4 observed at week 52 persisted to week 130. By a post-hoc analysis, there were no statistically significant increases from week 52 to week 130 in either desensitization success or SCD.

Extended treatment with VP250 was well-tolerated and desensitization observed at week 52 persisted between weeks 52 and 130. Treatment success was observed predominantly in younger participants with younger age at initiation of active therapy an important predictor of success.

The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with PeanuT (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents.

ARC004, the open-label follow-on study to PALISADE, used five dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals.

Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge (DBPCFC) and placebo arm (PTAH-naïve) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (Cohorts 1 and 3A) or non-daily (Cohorts 2, 3B, and 3C) dosing regimens; PTAH-naïve participants were built up to 300-mg/day PTAH, followed by maintenance dosing. At study completion, participants underwent an exit DBPCFC with doses up to 2000-mg peanut protein. Data were assessed using descriptive statistics.

Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n=256; PTAH-naïve, n=102). Among PTAH-continuing participants, exposure-adjusted adverse event (AE) rates were 12.94-17.54/participant-year (PY) and 25.95-42.49/PY in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate AEs. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, Cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naïve participants mirrored those of the PALISADE active arm.

Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

Current literature is inconsistent regarding the risk of severe side effects using accelerated induction protocols in Hymenoptera venom immunotherapy (VIT). In addition, several data indicate the influence of purity grade of venom preparation on tolerability. We evaluated the safety and tolerability of ultra-rush and rush build-up protocols using purified and non-purified venom preparations.

Retrospective single-center study of 581 VIT inductions (325 ultra-rush and 256 rush protocols) from 2005 to 2018 in 559 patients with bee and vespid venom allergy using aqueous purified (ALK SQ®) for ultra-rush protocol and aqueous non-purified (ALK Reless®) venom preparations for rush protocol.

Urticaria (8% vs. 3.1%, p = 0,013) and dose reductions (4.3% vs. 1.2%, p = 0,026) were significantly more frequent in the ultra-rush group. Overall rate of moderate-to-severe side effects (anaphylaxis ≥≥ grade 2 according to Ring and Meβmer) was low and did not differ significantly between protocols (p = 0.105). Severe events (grade 4 anaphylaxis) were not reported. Discontinuation rate was very low in both cohorts (0.6% vs 1.2%). The higher purity grade of venom preparations in the ultra-rush cohort did not improve tolerability. The bee venom group showed a non-significant trend towards higher incidence of mild reactions (urticaria), resulting in more frequent dose reductions and antiallergic therapy.

Rush and ultra-rush protocols show an excellent safety profile with only infrequent and mild anaphylactic reactions in bee and vespid venom allergy. Ultra-rush immunotherapy reduces the duration of the inpatient build-up phase setting and thus is viewed by the authors as preferred treatment in Hymenoptera venom allergic patients.

Allergic rhinitis (AR) is a chronic inflammatory immunoglobulin (Ig) E-mediated disease of the nasal mucosa that can be triggered by the inhalation of seasonal or perennial allergens. Typical symptoms include sneezing, rhinorrhea, nasal itching, nasal congestion and symptoms of allergic conjunctivitis. AR affects a quarter of the population in the United States of America and Europe.

AR has been shown to reduce work productivity in 36-59% of the patients with 20% reporting deteriorated job attendance. Moreover, 42% of children with AR report reduced at-school productivity and lower grades. Most importantly, AR impacts the patient’s quality of life, due to sleep deprivation. However, a proportion of patients fails to respond to conventional medication and opts for the allergen immunotherapy (AIT), which currently is the only disease-modifying therapeutic option. AIT can be administered by either subcutaneous (SCIT) or sublingual (SLIT) route. Both routes of administration are safe, effective, and can lead to tolerance lasting years after treatment cessation. Both innate and adaptive immune responses that contribute to allergic inflammation are suppressed by AIT. Innate responses are ameliorated by reducing local mast cell, basophil, eosinophil, and circulating group 2 innate lymphoid cell frequencies which is accompanied by decreased basophil sensitivity. Induction of allergen-specific blocking antibodies, immunosuppressive cytokines, and regulatory T and B cell phenotypes are key pro-tolerogenic adaptive immune responses.

A comprehensive understanding of these mechanisms is necessary for optimal selection of AIT-responsive patients and monitoring treatment efficacy. Moreover, it could inspire novel and more efficient AIT approaches.

Allergen immunotherapy (AIT) is the only disease-modifying treatment with evidence for sustained efficacy. However, it is poorly developed compared to symptomatic drugs. The main reasons come from treatment duration implying monthly injections during 3 to 5 years or daily sublingual use, and the risk of allergic side-effects. To become a more attractive alternative to lifelong symptomatic drug use, improvements to AIT are needed. Among the most promising new immunotherapy strategies is the use of bioparticles for the presentation of target antigen to the immune system as they can elicit strong T cell and B cell immune responses. Virus-like particles (VLPs) are a specific class of bioparticles in which the structural and immunogenic constituents are from viral origin. However, VLPs are ill-suited for use in AIT as their antigenicity is linked to structure. Recently, synthetic biology has been used to produce artificial modular bioparticles, in which supramolecular assemblies are made of elements from heterogeneous biological sources promoting the design and use of in vivo-assembling enveloped bioparticles for viral and non-viral antigens presentation. We have used a coiled-coil hybrid assembly for the design of an enveloped bioparticle (eBP) that present trimers of the Der p 2 allergen at its surface, This bioparticle was produced as recombinant and in vivo assembled eBPs in plant. This allergen biotherapeutic was used to demonstrate i) the capacity of plants to produce synthetic supramolecular allergen bioparticles, and ii) the immunomodulatory potential of naturally-assembled allergen bioparticles. Our results show that allergens exposed on eBPs induced a very strong IgG response consisting predominantly of IgG2a in favor of the TH1 response. Finally, our results demonstrate that rDer p 2 present on the surface of BPs show a very limited potential to stimulate the basophil degranulation of patient allergic to this allergen which is predictive of a high safety potential.

Food oral immunotherapy (OIT) has emerged as way to mitigate serious allergic reactions including life-threatening anaphylaxis related to accidental ingestion. However, gastrointestinal-related adverse effects of OIT have been reported and are often cited as reasons for discontinuation of therapy. We summarize recent research on the prevalence of eosinophilic esophagitis (EoE) in patients undergoing OIT.

We examined 12 recent studies on OIT for peanut, milk, walnut, egg, and wheat, which enrolled a total of 620 patients. Gastrointestinal symptoms were common during OIT, and while generally mild, 24 (3.9%) patients from the reviewed studies reported gastrointestinal symptoms that were significant enough to prompt discontinuation of OIT. Of these, two (0.3% of the total 620 patients or 8.3% of those with gastrointestinal symptoms) patients had biopsy-confirmed EoE. One of these patients was subsequently found to also have ulcerative colitis that had been previously undiagnosed.

EoE is a rare but concerning side effect of OIT. More research is needed to better elucidate both the OIT-related and patient-related factors that may predispose individuals to develop EoE. The presence of comorbid conditions and/or preexisting subclinical esophageal eosinophilia may account for some of cases of EoE identified during OIT.

Basophil activation tests (BATs) can closely monitor, in vitro, a patient’s propensity to develop type I hypersensitivity reactions. Because of their high specificity and sensitivity, BATs have become promising diagnostic tools, especially in cases with equivocal clinical histories, skin prick test results, and/or levels of specific IgE to allergen extracts. BATs also are useful as tools for monitoring the effects of treatment, since oral immunotherapy (OIT) studies report a diminution in patients’ basophil responsiveness over the course of OIT. This review will discuss the BAT findings obtained before, during, and after OIT for food allergy. We will mainly focus on the association of basophil responsiveness, and alterations in basophil surface markers, with clinical outcomes and other clinical features, such as blood levels of specific IgG and IgE antibodies. The detailed analysis of these correlations will ultimately facilitate the use of BATs, along with other blood biomarkers, to differentiate short-term desensitization versus sustained unresponsiveness and to improve treatment protocols. Given the critical anatomic location of mast cells adjacent to the many IgE+ plasma cells found in the gastrointestinal tissues of allergic individuals, we will also discuss the role of gastrointestinal mast cells in manifestations of food allergies.

There is a dearth of real-world evidence studies focused on allergy immunotherapy (AIT) use among patientswith allergic rhinitis (AR).

This study examined claims data of AR patients residing in the United States to assess patient characteristicsand health outcomes.

AR patients were identified in the IBM MarketScan database between January 1, 2014, and March 31, 2017. Patients receiving AIT were identified with relevant billing codes (earliest AIT claim for vaccine as the index date); patientswithout AIT were identified with claims that contained a diagnosis code for AR (earliest AR claim as the index date). All the patients were required to have continuous enrollment 12 months prior to and following their index date. AIT patients reaching 25+ injection claims were analyzed as a separate maintenance cohort. Patients were assessed for demographic characteristics, comorbid conditions, and health care utilization.

A total of 2,334,530 AR patients were included; 103,207 had at least one AIT claim, with 45,279 (43.9%) of thesepatients reaching maintenance. Patients who reached AIT maintenance presented higher rates of baseline comorbidities than both the full AIT cohort and the patients with no AIT claims, including asthma (34.6% versus 30.1% versus 7.5%) and upper respiratory tract infections (63.1% versus 60.3% versus 34.2%). From baseline to follow-up, maintenance AIT patients demonstrated reductions in all AR-related comorbidities assessed, along with reductions in all-cause and AR-related service utilization.

Patients initiating AIT presented the greatest need for therapeutic intervention, as evidenced by higher allergy-related comorbidities; those who reached maintenance demonstrated improved outcomes following the initiation oftherapy. Continued efforts to increase patient awareness and adherence to AIT are needed.

House dust mite (HDM) sublingual immunotherapy (SLIT) has proven to be effective for allergic rhinitis (AR), but its efficacy varies among patients. No candidate biomarkers for prediction of response to SLIT are available. Periostin, a matricellular protein, is involved in pathophysiology of AR, and its serum levels reflect airway allergic inflammation.

To evaluate the relationship between serum periostin levels and current rhinitis control before and after standardized quality (SQ)-HDM SLIT, and to investigate the role of periostin in predicting clinical response.

One hundred eleven subjects with HDM-induced AR were randomized to receive either SLIT plus pharmacotherapy or pharmacotherapy alone, for 48 weeks. At enrollment and the end of study, clinical characteristics and biomarkers that included serum periostin, serum HDM-specific IgE (s-IgE), total IgE, blood eosinophil counts, and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were measured. The association between clinical indices or biomarkers and clinical response to SLIT was analyzed.

A response to SLIT was recorded in 64% (32 of 50) patients. High serum periostin levels (>30.2 ng/mL) were associated with an effective response to SLIT, and the magnitude of RQLQ improvement was correlated with the level of serum periostin. The sensitivity and specificity based on receiver operating characteristic analysis for periostin were higher than those of s-IgE. Multivariate regression analysis showed that serum periostin was an independent factor for SLIT responders.

Serum periostin appears to be a useful biomarker for predicting the response to SQ-HDM SLIT in patients with AR.

A significant amount of medical literature has been published on the prevalence and treatment modalities of allergies to common household pets like dogs and cats. Although sensitization rates to horses are high in many urban areas, allergies to horses are rarely discussed. In order for allergists to treat effectively horse-allergic patients, they must be aware of various clinical presentations and treatment modalities that exist. A literature search was conducted in PubMED using the terms horse, immunotherapy, inhalant allergies, and food allergy limited to human studies from any period. What follows is a review of the prevalence, clinical presentations, and treatment modalities of horse aeroallergens and food allergies.