Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Management of Refractory Anaphylaxis: An Overview of Current Guidelines.

In this review, we compare different refractory anaphylaxis (RA) management guidelines focusing on cardiovascular involvement and best practice recommendations, discuss postulated pathogenic mechanisms underlining RA and highlight knowledge gaps and research priorities. There is a paucity of data supporting existing management guidelines. Therapeutic recommendations include the need for the timely administration of appropriate doses of aggressive fluid resuscitation and intravenous (IV) adrenaline in RA. The preferred second-line vasopressor (noradrenaline, vasopressin, metaraminol and dopamine) is unknown. Most guidelines recommend IV glucagon for patients on beta-blockers, despite a lack of evidence. The use of methylene blue or extracorporeal life support (ECLS) is also suggested as rescue therapy. Despite recent advances in understanding the pathogenesis of anaphylaxis, the factors that lead to a lack of response to the initial adrenaline and thus RA are unclear. Genetic factors, such as deficiency in platelet activating factor-acetyl hydrolase or hereditary alpha-tryptasaemia, mastocytosis may modulate reaction severity or response to treatment. Further research into the underlying pathophysiology of RA may help define potential new therapeutic approaches and reduce the morbidity and mortality of anaphylaxis.

Prevalence of tree nut allergy in Europe: A systematic review and meta-analysis.

In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published the first systematic review that summarized the prevalence of food allergy (FA) and food sensitization in Europe for studies published 2000-2012. However, only summary estimates for tree nut allergy (TNA) were feasible in that work. In the current update of that systematic review, we summarized the prevalence of tree nut allergy/sensitization to individual tree nuts. Six databases were searched for relevant papers published 2012-2021 and 17 eligible studies were added to the 15 studies already identified between 2000 and 2012, giving a total of 32 studies. Of the investigated tree nuts, meta-analysis was possible for hazelnut, walnut, almond, and in few cases, for cashew, and Brazil nut. The lifetime self-reported prevalence was 0.8% (95% CI 0.5-1.1) for hazelnut and 0.4% (0.2-0.9) for walnut. The point self-reported prevalence was 4.0% (2.9-5.2) for hazelnut, 3.4% (2.0-4.9) for Brazil nut, 2.0% (1.1-2.9) for almond, and 1.8% (1.1-2.5) for walnut. Point prevalence of food challenge-confirmed TNA was 0.04% (0.0-0.1) for hazelnut and 0.02% (0.01-0.1) for walnut. Due to paucity of data, we could not identify any meaningful and consistent differences across age groups and European regions.

Tolerance development in cow's milk-allergic children receiving amino acid-based formula with synbiotics: 36-Months follow-up of a randomized controlled trial (PRESTO Study).

The objective of the present study is to assess the rates of acquired tolerance to cow's milk (CM) after 36 months in subjects who consumed amino acid-based formula with synbiotics (AAF-S) or amino acid-based formula without synbiotics (AAF) during a 1-year intervention period in early life as part of the PRESTO study (Netherlands Trial Register number NTR3725). Differences in CM tolerance development between groups were analysed using a logistic regression model. Results show that the proportion of subjects (mean [±SD] age, 3.8 ± 0.27 years) who developed CM tolerance after 36 months was similar in the group receiving AAF-S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p = 0.253), that is, figures comparable to natural outgrowth of CM allergy. Our data suggest that the consumption of AAF and absence of exposure to CM peptides do not slow down CM tolerance acquisition.

How to diagnose IgE-mediated food allergy.

Immunoglobulin E (IgE)-mediated food allergy is an immune response, typically to a food protein. Accurate diagnosis reduces unnecessary dietary restrictions and economic and psychological burden on patients and caregivers but relies on a rigorous clinical history, specific IgE diagnostic tests and, where needed, oral food challenge. Increased awareness is needed around which patients to test for IgE-mediated food allergy, as well as terms commonly associated with IgE-mediated food allergy testing, in order to optimise patient diagnosis and management. Herein, we describe approaches to diagnosis of IgE-mediated food allergy, appropriate interpretation of results and risks of overtesting.

Prevalence estimates of eight big food allergies in Europe: Updated systematic review and meta-analysis.

In 2014, the European Academy of Allergy and Clinical Immunology published prevalence estimates for food allergy (FA) and food sensitization (FS) to the so-called eight big food allergens (i.e. cow's milk, egg, wheat, soy, peanut, tree nuts, fish and shellfish) in Europe for studies published between 2000 and 2012. The current work provides 10-year updated prevalence estimates for these food allergens. A protocol was registered on PROSPERO before starting the research (reference number CRD42021266657). Six databases were searched for studies published 2012-2021, added to studies published up to 2012, resulting in a total of 93 studies. Most studies were graded as at moderate risk of bias. The overall pooled estimates for all age groups of self-reported lifetime prevalence were as follows: cow's milk (5.7%, 95% confidence interval 4.4-6.9), egg (2.4%, 1.8-3.0), wheat (1.6%, 0.9-2.3), soy (0.5%, 0.3-0.7), peanut (1.5%, 1.0-2.1), tree nuts (0.9%, 0.6-1.2), fish (1.4%, 0.8-2.0) and shellfish (0.4%, 0.3-0.6). The point prevalence of food challenge-verified allergy were as follows: cow's milk (0.3%, 0.1-0.5), egg (0.8%, 0.5-1.2), wheat (0.1%, 0.01-0.2), soy (0.3%, 0.1-0.4), peanut (0.1%, 0.0-0.2), tree nuts (0.04%, 0.02-0.1), fish (0.02%, 0.0-0.1) and shellfish (0.1%, 0.0-0.2). With some exceptions, the prevalence of allergy to common foods did not substantially change during the last decade; variations by European regions were observed.

Frequency of food allergy in Europe: An updated systematic review and meta-analysis.

Food allergy (FA) is increasingly reported in Europe, however, the latest prevalence estimates were based on studies published a decade ago. The present work provides the most updated estimates of the prevalence and trends of FA in Europe. Databases were searched for studies published between 2012 and 2021, added to studies published up to 2012. In total, 110 studies were included in this update. Most studies were graded as moderate risk of bias. Pooled lifetime and point prevalence of self-reported FA were 19.9% (95% CI 16.6-23.3) and 13.1% (95% CI 11.3-14.8), respectively. The point prevalence of sensitization based on specific IgE (slgE) was 16.6% (95% CI 12.3-20.8), skin prick test (SPT) 5.7% (95% CI 3.9-7.4), and positive food challenge 0.8% (95% CI 0.5-0.9). While lifetime prevalence of self-reported FA and food challenge positivity only slightly changed, the point prevalence of self-reported FA, sIgE and SPT positivity increased from previous estimates. This may reflect a real increase, increased awareness, increased number of foods assessed, or increased number of studies from countries with less data in the first review. Future studies require rigorous designs and implementation of standardized methodology in diagnosing FA, including use of double-blinded placebo-controlled food challenge to minimize potential biases.

EAACI guidelines on the diagnosis of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.

Tolerance development in cow's milk-allergic infants receiving amino acid-based formula: A randomized controlled trial.

BACKGROUND: Tolerance development is an important clinical outcome for infants with cow's milk allergy. OBJECTIVE: This multicenter, prospective, randomized, double-blind, controlled clinical study (NTR3725) evaluated tolerance development to cow's milk (CM) and safety of an amino acid-based formula (AAF) including synbiotics (AAF-S) comprising prebiotic oligosaccharides (oligofructose, inulin) and probiotic Bifidobacterium breve M-16V in infants with confirmed IgE-mediated CM allergy. METHODS: Subjects aged ≤13 months with IgE-mediated CM allergy were randomized to receive AAF-S (n = 80) or AAF (n = 89) for 12 months. Stratification was based on CM skin prick test wheal size and study site. After 12 and 24 months, CM tolerance was evaluated by double-blind, placebo-controlled food challenge. A logistic regression model used the all-subjects randomized data set. RESULTS: At baseline, mean ± SD age was 9.36 ± 2.53 months. At 12 and 24 months, respectively, 49% and 62% of subjects were CM tolerant (AAF-S 45% and 64%; AAF 52% and 59%), and not differ significantly between groups. During the 12-month intervention, the number of subjects reporting at least 1 adverse event did not significantly differ between groups; however, fewer subjects required hospitalization due to serious adverse events categorized as infections in the AAF-S versus AAF group (9% vs 20%; P = .036). CONCLUSIONS: After 12 and 24 months, CM tolerance was not different between groups and was in line with natural outgrowth. Results suggest that during the intervention, fewer subjects receiving AAF-S required hospitalization due to infections.

Pharmacokinetics of adrenaline autoinjectors.

Anaphylaxis is a medical emergency with adrenaline acknowledged as the first-line therapy. It is therefore important that patients have access to self-injectable adrenaline in the community. Manufacturers have been requested by European Medicine Regulators to generate pharmacokinetic data for these autoinjector devices. For the first time, these data provide an insight into how individual devices work in different populations, and how they compare. We undertook a thorough literature search and also accessed grey literature, using searches of medicine regulators' websites and freedom of information requests. The data demonstrate that it takes at least 5-10 min to achieve early peak plasma concentration for most devices. The specific autoinjector device seems to be the most important determinant of pharmacokinetics, with different devices giving rise to different plasma adrenaline profiles. Needle length does not seem to be the most important factor; rather, the force and speed of injection (which varies from one device to another) is likely to be of greater importance. In general, peak plasma adrenaline concentration is lower and time-to-peak concentration longer with increased skin-to-muscle depth. However, it is difficult to draw conclusions with the current available data, due to a lack of head-to-head comparisons, small numbers of study participants and the failure to acknowledge the biphasic nature of intramuscular adrenaline absorption for analysis purposes.

Risk factors for severe reactions in food allergy: Rapid evidence review with meta-analysis.

This rapid review summarizes the most up to date evidence about the risk factors for severe food-induced allergic reactions. We searched three bibliographic databases for studies published between January 2010 and August 2021. We included 88 studies and synthesized the evidence narratively, undertaking meta-analysis where appropriate. Significant uncertainties remain with respect to the prediction of severe reactions, both anaphylaxis and/or severe anaphylaxis refractory to treatment. Prior anaphylaxis, an asthma diagnosis, IgE sensitization or basophil activation tests are not good predictors. Some molecular allergology markers may be helpful. Hospital presentations for anaphylaxis are highest in young children, yet this age group appears at lower risk of severe outcomes. Risk of severe outcomes is greatest in adolescence and young adulthood, but the contribution of risk taking behaviour in contributing to severe outcomes is unclear. Evidence for an impact of cofactors on severity is lacking, although food-dependent exercise-induced anaphylaxis may be an exception. Some medications such as beta-blockers or ACE inhibitors may increase severity, but appear less important than age as a factor in life-threatening reactions. The relationship between dose of exposure and severity is unclear. Delays in symptom recognition and anaphylaxis treatment have been associated with more severe outcomes. An absence of prior anaphylaxis does not exclude its future risk.

Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: A systematic review and meta-analysis.

It remains uncertain as to whether nutrient supplementation for the general population considered healthy could be useful in the prevention of RTIs, such as COVID-19. In this systematic review and meta-analysis, the evidence was evaluated for primary prevention of any viral respiratory tract infection (RTI) such as SARS-CoV-2, through supplementation of nutrients with a recognized role in immune function: multiple micronutrients, vitamin A, folic acid, vitamin B12, C, D, E, beta-carotene, zinc, iron and long-chain polyunsaturated fatty acids. The search produced 15,163 records of which 93 papers (based on 115 studies) met the inclusion criteria, resulting in 199,055 subjects (191,636 children and 7,419 adults) from 37 countries. Sixty-three studies were included in the meta-analyses, which was performed for children and adults separately. By stratifying the meta-analysis by world regions, only studies performed in Asia showed a significant but heterogeneous protective effect of zinc supplementation on RTIs (RR 0.86, 95% CI 0.7-0.96, I2  = 79.1%, p = .000). Vitamin D supplementation in adults significantly decreased the incidence of RTI (RR 0.89, 95% CI 0.79-0.99, p = .272), particularly in North America (RR 0.82 95% CI 0.68-0.97), but not in Europe or Oceania. Supplementation of nutrients in the general population has either no or at most a very limited effect on prevention of RTIs. Zinc supplementation appears protective for children in Asia, whilst vitamin D may protect adults in the USA and Canada. In 10/115 (8.7%) studies post-hoc analyses based on stratification for nutritional status was performed. In only one study zinc supplementation was found to be more effective in children with low zinc serum as compared to children with normal zinc serum levels.

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

BACKGROUND: The 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. METHODS: We 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. RESULTS: Continued 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. CONCLUSIONS: These 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.

Allergen immunotherapy and/or biologicals for IgE-mediated food allergy: A systematic review and meta-analysis.

BACKGROUND: There is substantial interest in immunotherapy and biologicals in IgE-mediated food allergy. METHODS: We searched six databases for randomized controlled trials about immunotherapy alone or with biologicals (to April 2021) or biological monotherapy (to September 2021) in food allergy confirmed by oral food challenge. We pooled the data using random-effects meta-analysis. RESULTS: We included 36 trials about immunotherapy with 2126 mainly child participants. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5.-21.4, high certainty); cow's milk (RR 5.7, 1.9-16.7, moderate certainty) and hen's egg allergy (RR 8.9, 4.4-18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300 mg or 1000 mg peanut protein was 2. Oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0-1.2, low certainty) or severe reactions in peanut allergy (RR 1,6, 0.7-3.5, low certainty), but may increase (mild) adverse reactions in cow's milk (RR 3.9, 2.1-7.5, low certainty) and hen's egg allergy (RR 7.0, 2.4-19.8, moderate certainty). Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8-3.8, moderate certainty). Results were unclear for other allergies and administration routes. There were too few trials of biologicals alone (3) or with immunotherapy (1) to draw conclusions. CONCLUSIONS: Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow's milk and hen's egg allergy. More research is needed about quality of life, cost and biologicals.

EAACI guidelines: Anaphylaxis (2021 update).

Anaphylaxis is a clinical emergency which all healthcare professionals need to be able to recognize and manage. The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline. The guideline was developed using the AGREE II framework and the GRADE approach. The evidence was systematically reviewed and recommendations were created by weighing up benefits and harms. The guideline was peer-reviewed by external experts and reviewed in a public consultation. The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase. The prompt use of intramuscular adrenaline as first-line management is recommended with the availability of adrenaline autoinjectors to patients in the community. Pharmacokinetic data should be provided for adrenaline autoinjector devices. Structured, comprehensive training for people at risk of anaphylaxis is recommended. Simulation training and visual prompts for healthcare professionals are suggested to improve the management of anaphylaxis. It is suggested that school policies reflect anaphylaxis guidelines. The evidence for the management of anaphylaxis remains mostly at a very low level. There is an urgent need to prioritize clinical trials with the potential to improve the management of patients at risk of anaphylaxis.

Development and validation of the food allergy severity score.

BACKGROUND: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. METHODS: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. RESULTS: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. CONCLUSION: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

Maternal anxiety and previous anaphylaxis are associated with alexithymia in young patients with food allergy.

BACKGROUND: Alexithymia is a multifaceted personality construct described as "a lack of words to express emotions" that includes difficulty identifying feelings, difficulty describing feelings and a concrete, externally oriented cognitive style. Among patients with food allergy (FA) alexithymia has been found higher than in general population and associated with dysfunctional coping strategies. Childhood traumatic experiences and/or dysfunctional parent-child relationship can contribute to alexithymia. The study aimed to explore possible associations between child alexithymia and mother alexithymia and anxiety, as well as previous anaphylaxis. METHODS: Sixty-five mother-child pairs have been recruited. Children had a medical diagnosis of FA. The Toronto Alexithymia Scale-20 was used to assess alexithymia in participants. The State-Trait Anxiety Inventory was used to assess trait anxiety in mothers. Statistical analysis was performed to investigate the influence of variables sex, previous anaphylaxis, and adrenaline auto-injector prescription on child and mother's alexithymia and to explore possible association between maternal and child alexithymia. RESULTS: A substantial percentage of children were alexithymic (21.5%) or borderline (33.8%), while mothers' frequencies were lower and in line with prevalence in general population. Child alexithymia was positively associated with previous anaphylaxis and mothers' trait anxiety (p < .05). Mother trait anxiety was also associated with maternal alexithymia. Furthermore, a positive association between child and mother alexithymia has been found. CONCLUSIONS: Clinicians must be aware of the role of alexithymia and its association with maternal anxiety and previous anaphylaxis in children with FA, encouraging seeking psychological support when needed. A multidisciplinary patient-centered approach should be put in place for the effective care of FA.

Prevention and management of allergic reactions to food in child care centers and schools: Practice guidelines.

Food allergy management in child care centers and schools is a controversial topic, for which evidence-based guidance is needed. Following the Grading of Recommendations Assessment, Development, and Evaluation approach, we conducted systematic literature reviews of the anticipated health effects of selected interventions for managing food allergy in child care centers and schools; we compiled data about the costs, feasibility, acceptability, and effects on health equity of the selected interventions; and we developed the following conditional recommendations: we suggest that child care centers and schools implement allergy training and action plans; we suggest that they use epinephrine (adrenaline) to treat suspected anaphylaxis; we suggest that they stock unassigned epinephrine autoinjectors, instead of requiring students to supply their own personal autoinjectors to be stored on site for designated at-school use; and we suggest that they do not implement site-wide food prohibitions (eg, "nut-free" schools) or allergen-restricted zones (eg, "milk-free" tables), except in the special circumstances identified in this document. The recommendations are labeled "conditional" due to the low quality of available evidence. More research is needed to determine with greater certainty which interventions are likely to be the most beneficial. Policymakers might need to adapt the recommendations to fit local circumstances.

Food allergy across the globe.

The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and diverse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will also discuss similarities and differences between FA guidelines.

AR101 Oral Immunotherapy for Peanut Allergy.

BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions. METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms. RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older. CONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).