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.

Diagnosing, managing and preventing anaphylaxis: Systematic review.

BACKGROUND: This systematic review used the GRADE approach to compile evidence to inform the European Academy of Allergy and Clinical Immunology's (EAACI) anaphylaxis guideline. METHODS: We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18 449 participants: 29 randomized controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarized narratively because studies were too heterogeneous to conduct meta-analysis. RESULTS: It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. There was also insufficient evidence about the impact of most anaphylaxis management and prevention strategies. Adrenaline is regularly used for first-line emergency management of anaphylaxis but little robust research has assessed its effectiveness. Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. We searched for but found little or no comparative effectiveness evidence about strategies such as fluid replacement, oxygen, glucocorticosteroids, methylxanthines, bronchodilators, management plans, food labels, drug labels and similar. CONCLUSIONS: Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.

Preventing food allergy in infancy and childhood: Systematic review of randomised controlled trials.

BACKGROUND: This systematic review of ways to prevent immediate-onset/IgE-mediated food allergy will inform guidelines by the European Academy of Allergy and Immunology (EAACI). METHODS: The GRADE approach was used. Eleven databases were searched from 1946 to October 2019 for randomized controlled trials (and large prospective cohort studies in the case of breastfeeding). The studies included heterogeneous interventions, populations, and outcomes and so were summarized narratively. RESULTS: Forty-six studies examined interventions to reduce the risk of food allergy in infancy (up to 1 year) or early childhood. The following interventions for pregnant or breastfeeding women and/or infants may have little to no effect on preventing food allergy, but the evidence is very uncertain: dietary avoidance of food allergens, vitamin supplements, fish oil, probiotics, prebiotics, synbiotics, and emollients. Breastfeeding, hydrolyzed formulas, and avoiding cow's milk formula may not reduce the risk of cow's milk protein allergy; however, temporary supplementation with cow's milk formula in the first week of life may increase the risk of cow's milk allergy. Introducing well-cooked egg, but not pasteurized raw egg, from 4 to 6 months probably reduces the risk of hen's egg allergy. Introducing regular peanut consumption into the diet of an infant at increased risk beginning from 4 to 11 months probably results in a large reduction in peanut allergy in countries with a high prevalence. These conclusions about introducing peanut are based on moderate certainty evidence, from single trials in high-income countries. CONCLUSIONS: Sixty percent of the included studies were published in the last 10 years, but much still remains to be understood about preventing food allergy. In particular, there is a need to validate the potential benefits of early introduction of food allergens in a wider range of populations.

Preventing immediate-onset food allergy in infants, children and adults: Systematic review protocol.

BACKGROUND: More than 17 million people across Europe have allergies to food and the burden of food allergies is increasing. In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published guidelines for preventing food allergy. Important research has been published since then and it is essential to ensure the guidelines reflect the latest evidence. A systematic review will be undertaken to help prepare new guidelines due to be published in 2020. METHODS: Eleven bibliographic databases will be searched from inception to 31 October 2019 for randomized controlled trials about any intervention designed to prevent the development of new cases of immediate-type/IgE-mediated food allergy in infants, children and adults. There are few randomized controlled trials about the impact of breastfeeding on food allergy so prospective cohort studies about breastfeeding with at least 1000 participants at general risk or 200 at high risk of food allergy will also be eligible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to assess the certainty of the evidence and tabulate summary data. The risk of bias in individual trials will be assessed using the Cochrane risk of bias tool. All data extraction and quality appraisal will be undertaken independently by two reviewers in partnership with a taskforce of EAACI members. CONCLUSIONS: Preventing food allergy has the potential to improve personal well-being and reduce societal healthcare costs. It is important that forthcoming European guidelines take the latest research into account. Past reviews have tended to focus on single interventions or combined food allergy with other outcomes, making it difficult to draw robust conclusions about potential impacts for policy and practice.

Systematic review of monotherapy with biologicals for children and adults with IgE-mediated food allergy.

Background: Biological therapies relieve symptoms in allergic inflammatory diseases so we systematically reviewed the evidence about whether biological monotherapy could benefit people with IgE-mediated food allergy. Methods: We searched six bibliographic databases from 1946 to 30 September 2021 for randomised and non-randomised controlled trials about biological monotherapy in people with IgE-mediated food allergy confirmed by oral food challenge. We used the Grading of Recommendations, Assessment, Development and Evaluation approach to narratively summarise findings from three trials with 118 participants. The studies were too heterogeneous and sparse to conduct meta-analysis. Results: We included one randomised trial about etokimab, one about omalizumab and one about the discontinued TNX-901. All were in people with peanut allergy in the USA, mostly aged 13+ years. There was a trend towards improved tolerance of peanut during treatment, with few side effects. However, we have very low certainty about the evidence due to the small number of trials and participants. No included trial reported on quality of life or cost-effectiveness. Conclusions: There is not yet enough certainty to support offering etokimab or omalizumab widely for food allergy. Clinicians may consider the merits for individuals, but large randomised trials with standardised measures are needed to confirm the safety, efficacy and most suitable candidates, doses and durations of treatment before more universal use.