Treatment Of Peanut Allergy Research Articles

Studies on Cashew and Shrimp-Oral Immunotherapy-Induced Changes in Allergen-Reactive CD4+ T Cells

Oral Immunotherapy (OIT) is a promising intervention for food allergic individuals and has been FDA-approved to treat peanut allergy. Various hitherto studies have probed the clinical efficacy and immune mechanism of OIT-induced desensitization to peanut, milk, and egg, although immunomodulatory effects of cashew and shrimp-OIT have not been investigated. Thus, we examined pre- vs. post-OIT PBMCs from 38 cashew (n=33) or shrimp (n=5) OIT treated participants.

P117 REAL-WORLD PERSPECTIVES OF HEALTH CARE PROVIDERS DELIVERING THE FIRST APPROVED TREATMENT FOR PEANUT ALLERGY

In January 2020, Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH) became the first treatment for Peanut Allergy (PA) approved by the US Food and Drug Administration (FDA). The adoption of innovative new therapies requires consideration of the skills, logistics and practicalities required for implementation.

P032 STUDIES ON CASHEW AND SHRIMP-ORAL IMMUNOTHERAPY-INDUCED CHANGES IN ALLERGEN-REACTIVE CD4+ T CELLS

Oral Immunotherapy (OIT) is a promising intervention for food allergic individuals, and has been FDA-approved to treat peanut allergy. Various hitherto studies have probed the clinical efficacy and immune mechanism of OIT-induced desensitization to peanut, milk, and egg, although immunomodulatory effects of cashew and shrimp-OIT have not been investigated. Thus, we examined pre- vs. post-OIT PBMCs from 38 cashew (n=33)- or shrimp (n=5)-OIT treated participants.

Open-label follow-on study evaluating the efficacy, safety, and quality of life with extended daily oral immunotherapy in children with peanut allergy.

BackgroundThe benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder‐dnfp (PTAH)—formerly AR101—has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy‐related quality of life.MethodsWe present a subset analysis of PALISADE‐ARC004 participants (aged 4–17 years) who received 300 mg PTAH daily for a total of ~1.5 (Group A, n = 110) or ~2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double‐blind, placebo‐controlled food challenge (DBPCFC); skin prick testing; peanut‐specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores.ResultsContinued maintenance with PTAH increased participants’ ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose‐limiting symptoms. Immune biomarkers showed a pattern consistent with treatment‐induced desensitization. Among PTAH‐continuing participants, the overall and treatment‐related exposure‐adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life.ConclusionsThese results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response.

What is the role of allergen immunotherapy in IgE-mediated food allergy?

In food allergy, allergen avoidance and emergency treatment are still therapeutic hallmarks but, recently, allergen immunotherapy (AIT), with different application routes, has gained more attention. In primary food allergy, oral immunotherapy has been frequently used in clinical trials. This year, an oral immunotherapy preparation for treatment of peanut allergy was licensed in Europe. In secondary food allergy, sublingual and subcutaneous extracts have been used in clinical trials, mostly with cross-reactive pollen allergens. As there is no AIT preparation licensed for this indication, therapy should only be started when there also is aneed for treating associated respiratory symptoms.

The route is the destination-novel forms of application of allergen immunotherapy

Allergen immunotherapy (AIT) is the only causal therapy of IgE-mediated allergies if allergen avoidance is not feasible. Already well established are subcutaneous (SCIT) and sublingual (SLIT) allergen application, and recently the first oral immunotherapy (OIT) for treating peanut allergy was approved. Interesting and promising new forms of allergen administration are intralymphatic (ILIT) and epicutaneous (EPIT) immunotherapy. Immunologic and clinical efficiency in terms of tolerance induction have been investigated in animal and clinical studies, including the first phase 3studies. The findings as well as advantages and disadvantages, potential risks and challenges that still have to be addressed before routine clinical application can be envisioned will be comprehensively presented and discussed.

Peanut allergy: Beyond the oral immunotherapy plateau.

BackgroundThere are a lack of disease‐modifying treatments for peanut allergy, which is lifelong in most instances. Oral immunotherapy has remained at the forefront of prospective treatments, though its efficacy is consistently undermined by the risk of adverse reactions and meager sustained effects.AimThis review discusses the current state of oral immunotherapy, its strengths and limitations, and the future of therapeutics for the treatment of peanut allergy.ConclusionThe persistence of peanut allergy is currently attributed to reservoirs of peanut‐specific memory B cells and Th2 cells, though the cellular and molecular interplay that facilitates the replenishment of peanut‐specific IgE remains elusive. Uncovering these events will prove critical for identification of novel targets as we forge ahead to a new age of peanut allergy treatment with biotherapeutics.

Contributions of the international plant science community to the fight against infectious diseases in humans-part 2: Affordable drugs in edible plants for endemic and re-emerging diseases.

SummaryThe fight against infectious diseases often focuses on epidemics and pandemics, which demand urgent resources and command attention from the health authorities and media. However, the vast majority of deaths caused by infectious diseases occur in endemic zones, particularly in developing countries, placing a disproportionate burden on underfunded health systems and often requiring international interventions. The provision of vaccines and other biologics is hampered not only by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, but also by challenges caused by distribution and storage, particularly in regions without a complete cold chain. In this review article, we consider the potential of molecular farming to address the challenges of endemic and re‐emerging diseases, focusing on edible plants for the development of oral drugs. Key recent developments in this field include successful clinical trials based on orally delivered dried leaves of Artemisia annua against malarial parasite strains resistant to artemisinin combination therapy, the ability to produce clinical‐grade protein drugs in leaves to treat infectious diseases and the long‐term storage of protein drugs in dried leaves at ambient temperatures. Recent FDA approval of the first orally delivered protein drug encapsulated in plant cells to treat peanut allergy has opened the door for the development of affordable oral drugs that can be manufactured and distributed in remote areas without cold storage infrastructure and that eliminate the need for expensive purification steps and sterile delivery by injection.

Preclinical development of plant-based oral immune modulatory therapy for haemophilia B.

SummaryAnti‐drug antibody (ADA) formation is a major complication in treatment of the X‐linked bleeding disorder haemophilia B (deficiency in coagulation factor IX, FIX). Current clinical immune tolerance protocols are often not effective due to complications such as anaphylactic reactions against FIX. Plant‐based oral tolerance induction may address this problem, as illustrated by the recent first regulatory approval of orally delivered plant cells to treat peanut allergy. Our previous studies showed that oral delivery of plant cells expressing FIX fused to the transmucosal carrier CTB (cholera toxin subunit B) in chloroplasts suppressed ADA in animals with haemophilia B. We report here creation of the first lettuce transplastomic lines expressing a coagulation factor, in the absence of antibiotic resistance gene. Stable integration of the CTB‐FIX gene and homoplasmy (transformation of ˜10 000 copies in each cell) were maintained in both T1 and T2 generation marker‐free plants. CTB‐FIX expression in lyophilized leaves of T1 and T2 marker‐free plants was 1.0–1.5 mg/g dry weight, confirming that the marker excision did not affect antigen levels. Oral administration of CTB‐FIX to Sprague Dawley rats at 0.25, 1 or 2.5 mg/kg did not produce overt adverse effects or toxicity. The no‐observed‐adverse‐effect level (NOAEL) is at least 2.5 mg/kg for a single oral administration in rats. Oral administration of CTB‐FIX at 0.3 or 1.47 mg/kg either mixed in food or as an oral suspension to Beagle dogs did not produce any observable toxicity. These toxicology studies should facilitate filing of regulatory approval documents and evaluation in haemophilia B patients.

Treatment of Peanut Allergy.

1. Amy Burris, MD*,† 2. Theresa Bingemann, MD*,† 1. *Department of Medicine: Allergy, Immunology, and Rheumatology and 2. †Division of Pediatric Allergy and Immunology, University of Rochester Medical Center, Rochester, NY Peanut allergy (PA) affects 0.5% to 2% of children and is often a persistent condition that poses the risk of life-threatening reactions on exposure to peanut. It is the most common food allergy to cause anaphylaxis and death. Because allergy testing does not predict the severity of reactions, it is imperative that peanut-allergic children have access to epinephrine autoinjectors at all times. Although cutaneous reactions, including generalized urticaria, angioedema, and atopic dermatitis, are the most common, anaphylaxis accounts for more than one-third of reactions. Recently, research has focused on prevention strategies for PA. In high-risk infants, early introduction of peanut at younger than 11 months of age plays a crucial role in preventing PA. Conversely, avoidance of peanut is associated with increased risk of PA. Guidelines recommend early introduction of peanut to infants with no eczema or mild to moderate eczema. Infants with severe eczema should be promptly referred to an allergist for evaluation of peanut sensitization before introduction. Disruption of the skin barrier, as with eczema, plays a role in the development of food allergy. Transcutaneous exposure of food allergens may promote allergic sensitization, whereas allergen exposure through the gut may promote tolerance. Studies show that increased environmental peanut exposure leads to increased risk of PA, especially in children with eczema. Aggressive emollient therapy early in life may decrease the risk of developing eczema. Studies examining the role of early emollient therapy and development of food allergy are ongoing. The cross-reactivity between peanut allergens and environmental allergens means that apparent sensitization to peanut does not necessarily …

Emerging developments in the forefront of peanut oral immunotherapy.

Despite the COVID-19 pandemic, progress continued in the field of peanut oral immunotherapy over the past 12 to 18 months. Of importance, the first oral immunotherapy product for the treatment of peanut allergy was approved by the US Food and Drug Administration in January 2020. Suggested modifications to the practice of oral immunotherapy, some of which may have lasting impacts, were circulated as a result of the pandemic. New advances in pathophysiology, sustained unresponsiveness, quality of life, safety, and cost effectiveness were also published. During 2020, COVID-19 influenced the daily practice of allergy and immunology, with peanut oral immunotherapy being no exception. However, clinicians now have a FDA-approved treatment option for peanut allergy in children, a welcome development for a difficult disease. Future research is needed to clarify several knowledge deficits surrounding the best use of peanut OIT.

Current developments in the treatment of peanut allergy

AbstractPeanut allergy is a potentially life-threatening disease because it leads to severe allergic reactions, especially in children but also in adults. So far, allergen avoidance is the most effective therapy for treating peanut allergy. In this article, current developments of peanut allergy specific immunotherapy are critically discussed based on the existing literature. These include sublingual, epicutaneous and oral peanut immunotherapy. Nonspecific treatment approaches with new-targeted antibodies such as anti-IgE (omalizumab) or anti-IL-4/IL-13 receptor antibodies (dupilumab) can also be used to treat peanut allergy with regard to the mode of action of these antibodies. Multiple studies are already available for omalizumab and are currently performed with dupilumab. Whether and which therapies for the treatment of peanut allergy will be available on the market in the future is not only relevant in terms of clinical effectiveness in the sense of a long-term stable increase in the threshold level, but also in terms of the tolerability in everyday life of affected patients.

Basophil activation tests identify a peanut OIT subgroup with improved safety and outcomes

Oral immunotherapy (OIT) treatment for peanut allergy is now FDA approved for treatment of peanut allergic patients. The need for accurate and robust prognostic biomarkers to aid in patient selection is critical. We investigated the long-term safety of peanut OIT from our POISED study, and the potential role of BATs in predicting adverse events during long-term OIT and double-blind-placebo-controlled-food challenges (DBPCFCs).

AIT: New Avenues in Allergen Immunotherapy.

During the last decades a substantial increase of allergic diseases has been noticed including allergic asthma and rhinoconjunctivitis as well as food allergies. Since efficient avoidance of airborne - and often hidden - food allergens is not possible, allergen immunotherapy (AIT) is the only causative treatment with the goal of inducing allergen tolerance in affected individuals. Efficacy as well as safety of AIT significantly depends on how the allergen is presented to the immune system, meaning both the route and the form of its application. Here, new ways of allergen administration have lately been explored, some of which are auspicious candidates for successful implementation in the therapeutic management of immediate-type allergies. While the first oral AIT has been approved recently by the FDA for the treatment of peanut allergy, further interesting routes of allergen application include either epicutaneous, intradermal, intranasal, or intralymphatic delivery. Besides, rather the immunologically relevant peptides instead of whole allergen may be administered to develop tolerance. In this chapter, we will describe these new and promising avenues of allergen application in the field of AIT. In addition, we will discuss their potential for future treatment of IgE-mediated allergic diseases enhancing therapeutic efficiency while further minimizing the risks of adverse events.

Epicutaneous immunotherapy for treatment of peanut allergy: Follow-up from the Consortium for Food Allergy Research

Consortium for Food Allergy Research investigators previously reported 52-week outcomes from a randomized controlled trial of peanut epicutaneous immunotherapy, observing modest and statistically significant induction of desensitization, highest in children ages 4 to 11 years. We sought to evaluate changes in efficacy, safety, and mechanistic parameters following extended open-label peanut epicutaneous immunotherapy. Peanut-allergic participants (4-25 years) received 52 weeks of placebo (PLB), Viaskin Peanut 100 μg (VP100) or 250 μg (VP250), and then crossed over to VP250 for PLB (PLB-VP250) and VP100 (VP100-VP250) participants and continued treatment for VP250 participants (total= 130 weeks of active epicutaneous immunotherapy). Efficacy was assessed by double-blind, placebo-controlled food challenge (5044 mg peanut protein), and adherence, safety, and mechanistic parameters were evaluated. At week 130, desensitization success was achieved in 1 of 20 (5%) PLB-VP250, 5 of 24 (20.8%) VP100-VP250, and 9 of 25 (36%) VP250 participants, with median successfully consumed dose 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 (interquartile range, 5.2-9.1) versus 9.4 years (interquartile range, 7.6-12.8) for failures (P< .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 successfully consumed dose. 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.

A study to assess current approaches of allergists in European countries diagnosing and managing children and adolescents with peanut allergy.

Food allergy is documented to result in considerable morbidity, negative impact on quality of life, and substantial medical care costs. Although anecdotal data suggest widely varying practices in the diagnosis and management of food allergies, the diversity and relative frequency of these practices have not been documented. A questionnaire was developed evaluating allergists' management approaches of individuals with peanut allergy (PA) in Germany (DE), France (FR), and the United Kingdom (UK). Here, we report the survey results from a total of 109 allergists from DE, FR and the UK. They reported to confirm PA at initial diagnosis using skin prick test (≥60%), while allergists from DE and FR reported using allergen-specific IgE testing more (>86%) compared to the UK (<50%). At initial diagnosis, oral food challenge was used less in DE (13%) and FR (14%) and very rarely in the UK (3%) to confirm diagnosis. Recognition of acute reactions, use of adrenaline auto-injectors and allergen avoidance were reported to be discussed with the patient/caregiver at the initial office visit by most allergists (>75%). Half of the responders reported assessing the patient's quality of life. 63% allergists reported retesting for PA resolution at a later date, with 45% allergists indicated to recommend ingestion of a normal serving of peanut regularly upon resolution. Lack of effective PA treatment was reported to be a 'very significant' barrier for optimal PA treatment, with allergists being less than 'moderately familiar' with data from clinical trials testing new treatments options for PA. Lastly, allergists stated that the severity of patient's PA ranked as the most important factor in their decision to recommend oral immunotherapy for PA treatment. This survey provides essential insights into the practice of allergists and highlights some areas that would inform strategies for education and improving PA healthcare.

A044 SPECIFIC PEANUT EPITOPES AS A BIOMARKER FOR DESENSITIZATION DURING EPICUTANEOUS IMMUNOTHERAPY

Epicutaneous immunotherapy (EPIT) is under investigation for the treatment of peanut allergy. Existing biomarkers used in the diagnosis of peanut allergy are not adequate for quantifying desensitization during immunotherapy. We sought to assess performance of the Bead Based Epitope Assay (BBEA), which enables simultaneous quantification of antibodies recognizing sequential epitopes, in predicting desensitization during EPIT.

Epicutaneous immunotherapy protects cashew-sensitized mice from anaphylaxis.

BackgroundThe prevalence of tree nut allergy has increased worldwide, and cashew has become one of the most common food allergens. More critically, cashew allergy is frequently associated with severe anaphylaxis. Despite the high medical need, no approved treatment is available and strict avoidance and preparedness for prompt treatment of allergic reactions are considered dual standard of care. In the meantime, Phase III study results suggest investigational epicutaneous immunotherapy (EPIT) may be a relevant and safe treatment for peanut allergy and may improve the quality of life for many peanut allergic children.ObjectiveWe aimed to evaluate the capacity of EPIT to provide protection against cashew‐induced anaphylaxis in a relevant mouse model.MethodsThe efficacy of EPIT was evaluated by applying patches containing cashew allergens to cashew‐sensitized mice. As negative control, sham mice received patches containing excipient. Following treatment, mice were challenged orally to cashew and anaphylactic symptoms, as well as plasmatic levels of mast‐cell proteases (mMCP)‐1/7, were quantified.ResultsOf 16 weeks of EPIT significantly protects against anaphylaxis by promoting a faster recovery of challenged mice. This protection was characterized by a significant reduction of temperature drop and clinical symptoms, 60 minutes after challenge. This was associated with a decrease in mast‐cell reactivity as attested by the reduction of mMCP‐1/7 in plasma, suggesting that EPIT specifically decrease IgE‐mediated anaphylaxis.ConclusionWe demonstrate that EPIT markedly reduced IgE‐mediated allergic reactions in a mouse model of cashew allergy, which suggests that EPIT may be a relevant approach to treating cashew allergy.

Oral Immunotherapy for Food Allergy-a US Regulatory Perspective.

The recent approval of Palforzia for treatment of peanut allergy by the US Food and Drug Administration (USFDA) predicts that additional products for oral immunotherapy (OIT) are on the horizon. In this article, the authors review the legal framework by which the USFDA regulates products for OIT of food allergy and the clinical data that demonstrated that the safety and effectiveness profile of Palforzia supported approval and conclude with a discussion of oral food challenge (OFC) as a clinical endpoint to demonstrate safety and effectiveness of OIT products.

Food allergy: Epicutaneous immunotherapy.

The goal of allergen-specific immunotherapy for treatment of immunoglobulin E (IgE) mediated food allergy is to safely and effectively modify the allergic response, providing protection against anaphylaxis via ongoing exposure to the triggering allergen. Targeted allergen exposure via application of allergen to the epidermis has emerged as a potentially promising approach to desensitization. Epicutaneous immunotherapy (EPIT) uses allergen embedded on an adhesive patch secured to the skin. This allows for long-lasting allergen exposure, with subsequent antigen uptake and trafficking by skin antigen-presenting cells to regional lymph nodes, which produce immunomodulatory effects in a manner that is noninvasive and limits exposure of allergen to the systemic circulation when applied to intact skin. As such, EPIT is overall well tolerated; local application site reactions are common, but systemic adverse effects are infrequent compared with other forms of immunotherapy. For peanut allergy, EPIT may increase the dose-triggering threshold in some individuals with peanut-allergy, especially younger children, but induction of remission has not been closely studied, and reliable predictors of clinical response are lacking. With U.S. Food and Drug Administration approved treatment for peanut allergy now available, the precepts of shared decision-making will be crucial in discussions with patients and their families with regard to treatment options.