Efficacy, safety and quality of life in a multicenter, randomized, placebo-controlled trial of low-dose peanut oral immunotherapy in children with peanut allergy

BACKGROUND: Only 2 small placebo-controlled trials on peanut oral immunotherapy (OIT) have been published. OBJECTIVE: We examined the efficacy, safety, immunologic parameters, quality of life (QOL), and burden of treatment (BOT) of low-dose peanut OIT in a multicenter, double-blind, randomized placebo-controlled trial. METHODS: A total of 62 children aged 3 to 17 years with IgE-mediated, challenge-proven peanut allergy were randomized (1:1) to receive peanut OIT with a maintenance dose of 125 to 250 mg peanut protein or placebo. The primary outcome was the proportion of children tolerating 300 mg or more peanut protein at oral food challenge (OFC) after 16 months of OIT. We measured the occurrence of adverse events (AEs), immunologic changes, and QOL before and after OIT and BOT during OIT. RESULTS: Twenty-three of 31 (74.2%) children of the active group tolerated at least 300 mg peanut protein at final OFC compared with 5 of 31 (16.1%) in the placebo group (P < .001). Thirteen of 31 (41.9%) children of the active versus 1 of 31 (3.2%) of the placebo group tolerated the highest dose of 4.5 g peanut protein at final OFC (P < .001). There was no significant difference between the groups in the occurrence of AE-related dropouts or in the number, severity, and treatment of objective AEs. In the peanut-OIT group, we noted a significant reduction in peanut-specific IL-4, IL-5, IL-10, and IL-2 production by PBMCs compared with the placebo group, as well as a significant increase in peanut-specific IgG4 levels and a significant improvement in QOL; 86% of children evaluated the BOT positively. DISCUSSION: Low-dose OIT is a promising, effective, and safe treatment option for peanut-allergic children, leading to improvement in QOL, a low BOT, and immunologic changes showing tolerance development

APPEAL-2: A pan-European qualitative study to explore the burden of peanut-allergic children, teenagers and their caregivers

Background: Allergy to Peanuts ImPacting Emotions And Life (APPEAL-1) was a recent European multi-country questionnaire survey that highlighted the negative impacts of peanut allergy (PA) on quality of life. A follow-on qualitative study, APPEAL-2, further assessed the burden of PA and associated coping strategies through semi-structured interviews. Objective: To gain qualitative insight on the strategies used to cope with and manage PA and the impact of these strategies on the quality of life of children, teenagers and caregivers. Methods: This cross-sectional qualitative study was conducted in eight European countries: the United Kingdom, France, Germany, Ireland, Spain, Italy, Denmark and the Netherlands. Semi-structured interviews were conducted with children (aged 8-12 years) and teenagers (aged 13-17 years) with self-/proxy-reported moderate or severe PA and with parents/caregivers of children or teenagers (aged 4-17 years) with moderate or severe PA. Data were analysed using thematic analysis; data saturation was assessed. Two conceptual models were developed to illustrate the impacts of PA and coping strategies used to manage them for (a) individuals with PA and (b) parents/caregivers of children with PA. Results: 107 participants were interviewed: 24 children, 39 teenagers and 44 caregivers. The conceptual models illustrated themes related to coping and control, driven by the fear of PA reactions, and the associated emotional, social, relationship and work impacts. Factors moderating these impacts included social attitudes and support, child-caregiver relationship and coping strategies used. Conclusions and Clinical Relevance: The APPEAL-2 results substantiate the findings of APPEAL-1; the results also suggest that the severity of experience with PA may not correlate with perception of its overall burden and show variable impacts by country

APPEAL‐1: A pan-European survey of patient/caregiver perceptions of peanut allergy management

Background: Peanut allergy (PA) is associated with marked quality‐of‐life (QoL) impairment. However, data are lacking on the experience and impact of living with PA from the perspectives of persons with PA (PwPA) and their caregivers. A llergy to P eanuts imP acting E motions A nd L ife study 1 (APPEAL‐1) was a pan‐European survey investigating these perspectives. This first of two articles reports clinical characteristics of PwPA and PA management practices. Methods: APPEAL‐1 was a quantitative, online survey conducted in eight European countries, developed by eight representatives of patient advocacy groups and five healthcare professionals and researchers. Eligible participants included adults with PA and parents/caregivers of PwPA who responded by self‐report and provided proxy‐report for the PwPA under their care. Data were summarised using nonweighted descriptive statistics. Results: Of 1846 completed/analysed questionnaires, 528 were from adults with PA (self‐report); 437 by proxy for children with PA (34 aged 0‐3 years, 287 aged 4‐12 years, 116 aged 13‐17 years); 881 from parents/caregivers (self‐report). Of PwPA (N=965), 95% reported diagnosis by healthcare professionals, mostly by clinical history and peanut‐specific allergy testing. Rates of allergic rhinitis, asthma, and other food allergies in PwPA were 50%, 42%, and 79%, respectively. Only 31% of PwPA received HCP advice/support following their worst allergic reaction, and 28% had not been prescribed an adrenaline auto‐injector. Results were similar by country but varied by age group. Conclusions: The APPEAL‐1 findings contribute to greater understanding of PA impact on PwPA, caregivers, and family members and the need for improved PA management across Europe

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 similar to 1.5 (Group A, n = 110) or similar to 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

Understanding the challenges faced by adolescents and young adults with allergic conditions:a systematic review

BACKGROUND: Adolescence represents a vulnerable time for individuals with asthma and allergic conditions. They suffer an unexpected degree of morbidity. This systematic review aimed to understand the challenges faced by adolescents and young adults with these conditions. METHODS: A systematic literature search was undertaken across eight databases. References were checked by two reviewers for inclusion. Study data were extracted, and their quality was assessed in duplicate. A narrative meta-synthesis was undertaken. RESULTS: A total of 108 papers describing 106 studies were retrieved, most focused on asthma. Five themes were identified across studies: (a) Health-related quality of life-impairment was associated with poor disease control, psychosocial issues, adolescent-onset allergic disease and female sex; (b) Psychological factors-asthma and food allergy were associated with anxiety and depression, atopic dermatitis was associated with suicidal ideation, and that parental emotional support may be protective; (c) Adherence-suboptimal adherence was associated with older age, barriers to medication usage, poor symptom perception and failure to take responsibility, and positive factors were routines, simpler treatment regimes, better knowledge and perceptions about medications; (d) Self-management-facilitated by education, knowledge and a positive attitude; and (e) Supportive relationships-families could modify barriers to adherence and foster positive views about self-management, adolescents suggested that their peers should be more involved in supporting them, and adolescents also wished to have support from nonjudgemental healthcare professionals. CONCLUSIONS: We have some understanding of the challenges faced by adolescents with asthma, less so for other allergic conditions. This knowledge will be used to support guidelines for managing adolescents

A practical toolbox for the effective transition of adolescents and young adults with asthma and allergies - an EAACI Position paper

Adolescence is a critical stage of rapid biological, emotional and social change and development. Adolescents and young adults (AYA) with asthma and allergies need to develop the knowledge and skills to self-manage their health independently. Healthcare professionals (HCP), parents and their wider network play an essential role in supporting AYA in this process. Previous work showed significant limitations in transition care across Europe. In 2020, the first evidence-based guideline on effective transition for AYA with asthma and allergies was published by EAACI. We herein summarize practical resources to support this guideline's implementation in clinical practice. For this purpose, multi-stakeholder Task Force members searched for resources in peer review journals and grey literature. These resources were included if relevant and of good quality, and were pragmatically rated for their evidence-basis and user friendliness. Resources identified covered a range of topics and targeted healthcare professionals, AYA, parents/carers, schools, workplace, and wider community. Most resources were in English, web-based and had limited evidence-basis. This position paper provides a valuable selection of practical resources for all stakeholders to support effective transitional care for AYA with asthma and allergies. Future research should focus on developing validated, patient-centred tools to further assist evidence-based transition care

Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)

BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.</p

Airlines provide too little information for allergy sufferers!

&lt;jats:title&gt;Summary&lt;/jats:title&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Introduction&lt;/jats:title&gt; &lt;jats:p&gt;Allergic reactions are reported to account for approximately 2–4% of all medical emergencies on commercial airline flights. In 2016, the International Air Transport Association (IATA) published recommendations on risk prevention in severe allergies.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Methods&lt;/jats:title&gt; &lt;jats:p&gt;Using a written questionnaire and an internet search, an investigation was conducted on the extent to which airlines operating in Germany have implemented the IATA recommendations and, e.g., offer peanut/nut allergy sufferers appropriate measures.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Results&lt;/jats:title&gt; &lt;jats:p&gt;Only 14 of the 104 airlines contacted responded to the written survey. Of 115 airlines, 72 provided information for allergy sufferers on their homepage, but mostly in insufficient detail. No results were found for the search term “allergy” (or “Allergie”) on the websites of 43 airlines. The information on the individual airlines has been summarized in table form.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Discussion&lt;/jats:title&gt; &lt;jats:p&gt;The information offered by many airlines for passengers with allergies is insufficient. To offer greater guidance, updated information has been formulated in German and English, and its use is recommended.&lt;/jats:p&gt; &lt;/jats:sec&gt

APPEAL-1:A multiple-country European survey assessing the psychosocial impact of peanut allergy

Background: Peanut allergy (PA) is a common, potentially life‐threatening, and typically lifelong condition with a significant burden of illness. However, information is lacking on how persons with PA (PwPA) and their caregivers perceive the psychosocial impact of living with PA. The Allergy to Peanuts imPacting Emotions And Life study 1 (APPEAL‐1) survey, conducted across Europe, investigated the experience and impact of living with PA. Here, we report data evaluating the psychosocial impact of PA on PwPA and their caregivers. Methods: APPEAL‐1 was an online survey conducted in 8 European countries. Representatives of 8 patient advocacy groups and 5 healthcare‐research specialists developed the survey. Eligible respondent groups included: adults diagnosed with PA (self‐report); parent/nonparent caregivers (proxy‐report for a child with PA); and parent/nonparent caregivers (self‐report of PA impact on themselves). Results: Of 1846 total study respondents, 419 were adults with PA (self‐report); 546 were parents/ caregivers (proxy‐report) ; 881 were parents/caregivers (self‐report). Most respondents reported lifestyle restrictions regarding food (84‐93%) and additional domains including parties and socializing, holiday activities and destinations, and taking public transport (53‐89%). Approximately 40% rated themselves as “very” frustrated and “very” stressed. Two‐thirds (65%) felt socially isolated; 43% were bullied. Less than half felt confident in knowing when to use an adrenaline autoinjector. Several intercountry differences were observed such as high levels of uncertainty and stress in respondents from Ireland, highest rates of anxiety in respondents from Germany, and social exclusion and isolation most common in respondents from France. Conclusions: PA imposes an adverse psychosocial impact on patients and caregivers, leading to frustration, stress, and isolation. Attention to the impact of PA is needed in research and clinical practice to improve PA healthcare and public education programs