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Future of food allergy

Declaration of sponsorship Novartis Pharma AG
Read time: 50 mins
Last updated:4th Aug 2021
Published:4th Aug 2021

Find out what the future holds for the diagnosis and treatment of food allergy by exploring:

  • The unmet needs of food allergy in our expert interview with Dr Alexandra Santos
  • Treatments currently being investigated or making their way to clinical practice in our infographic
  • Novel developments in diagnostic testing, such as the basophil and mast cell activation tests

Unmet needs in food allergy

Improving care is a multifaceted challenge, involving the development of new preventative measures and treatment as well as fostering proactive partnerships with patients to increase their educational awareness of the risks associated with food allergies1.

Instead of fear-based decisions, informed patients will then have the tools necessary to make evidence-based decisions and will be better able to manage the risks they face each day1.

Join Dr Alexandra Santos below where she describes the four key current unmet needs faced by patients with food allergy.

What are the unmet needs in the prevention of food allergy?

In 2015, the seminal Learning Early About Peanut Allergy (LEAP) study showed that the early introduction of peanut to infants had a significant positive effect in the prevention of peanut allergy2,3.

A key unmet need in the prevention of food allergy is the need to enhance and optimise the implementation of early food introduction to prevent the development food allergy1

Following the results of the LEAP study, and others, the European Academy of Allergy and Clinical Immunology (EAACI) and American Academy of Allergy, Asthma & Immunology (AAAAI) were updated in 2020 to add recommendations for the introduction of egg and peanut between the ages of four and six months4,5. However, challenges still remain.

A systematic review of twenty-eight food allergy prevention guidelines (1999–2019) was conducted to comprehensively appraise their quality for health professional use6.

Twenty-five guidelines were found to make recommendations on exclusive breastfeeding, AAACI, EAACI, Asia pacific association of paediatric allergy, Respirology & immunology (APAPARI), and Australasian Society of Clinical Immunology and Allergy (ASCIA). However, several guidelines made no exclusive feeding recommendations, such as the National Institute of Allergy and Infectious Diseases (NIAID) guidelines6.

Of the guidelines that did make recommendations, six recommended "exclusive/predominantly exclusive breastfeeding for at least 4 months” and seven recommended "exclusive breastfeeding for 6 months or around 6 months or at least 6 months"6.

While guideline recommendations vary, all recommend the early introduction of food within a 4–6 month range6

Twenty-seven guidelines make recommendations regarding the timing of solid food introduction into the infant diet. While these recommendations had a high variability, all were within a 4–6 month range. Specifically, sixteen guidelines recommend that common food allergen introduction should not be delayed6.

Notably, six documents were updated following the publication of the LEAP study to include peanut allergy specific information6.

Some guidelines also stratify patients based on risk, such as NIAID and American Academy of Pediatrics guidelines. Conversely, several guidelines have a universal introduction of early allergens6. A qualitative analysis of the EAT study (N=1,303) also revealed three main challenges to the early introduction of allergenic food3:

  • Refusal of some children to consume allergenic food
  • Caregiver concern over the potential for a reaction
  • Practical problems associated with the regimen compromising caregiver capacity to persist

There is also still little evidence available concerning the optimal dose and timing of allergenic foods for the prevention of food allergy7.

What are the unmet needs in the diagnosis of food allergy?

As the prevalence of food allergy increases, it is becoming ever more important to have accurate newer diagnostic tools that provide objective evidence and prevent the misdiagnosis of food allergy8.

Currently, the oral food challenge is the gold standard for identifying the threshold of responsiveness as well as diagnosis and monitoring food allergy. However, the procedure is burdensome, requiring a team of specialised health professionals to ensure the safety of the patient during the challenge9.

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Emerging diagnostics for food allergy

While the clinical history remains the most valuable tool to reach an accurate diagnosis, several new objective biomarkers are currently being investigated, or are beginning to make their way into clinical practice21.

See Dr Alexandra Santos below for a brief overview of the diagnostic tests that are currently making their way into clinical trials.

Can IgE to individual allergen molecules be detected?

A recent advance in diagnostic testing for food allergy is component-resolved diagnosis (CRD), a diagnostic test utilising specific IgE to single allergens or components21.

CRD enables the identification of specific IgE against both major and minor allergens. Panallergens are allergens present in different sources and can cause IgE cross-reactivity. Examples include profilins, procalcins, non-specific lipid transfer proteins, and Bet v 1 homologues21. This increased capacity of CRD to identify and characterise specific molecules allows for a greater ability to21,22:

  • Predict the evolution of the allergic process
  • Differentiate species-specific and cross-reactive allergens
  • Determine the risk of a severe reaction
  • Guide and stratify the outcome of the OFC
  • Discriminate against primary food allergies and secondary sensitisation

In clinical practice, this allows CRD to help improve the accuracy of diagnostic testing, although the oral food challenge still remains the gold standard due to its greater specificity and sensitivity22.

Are basophil activation tests being used in clinical practice?

A novel test that is progressively transitioning into clinical practice is the basophil activation test (BAT)23. Processed within hours, flow cytometry is used to scan the surface of allergen-stimulated basophils to detect the expression of activation markers, such as CD63 and CD203c, following exposure to allergens24.

Functioning like an in vitro OFC, food extracts that are suspected of causing the allergic reaction are exposed to basophils to assess whether they degranulate upon stimulation24

BAT has been assessed for a variety of different food allergies and has reported sensitivity ranges from 77–98% and specificity from 75–100%, displaying a higher accuracy than SPT and sIgE23,24–33. In a more recent study that assessed the performance of BAT as a diagnostic marker for peanut allergy (N=104), BAT was shown to be superior to other diagnostic tests in differentiating peanut allergy and tolerance, have 100% specificity, and reduce the need for OFCs34. BATs have also been shown to correlate with severity of reaction at food challenge35.

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Investigational treatments for food allergy

The last decade of research has led to advances in the understanding of the pathophysiology of food allergy. Novel immunotherapies, biologic treatments, and therapies in the early stages of clinical trials offer the potential for increased safety, administration, and lasting tolerance38.

Join Dr Sharon Chinthrajah below, to discover the exciting developments in food allergy treatment that are currently under investigation39.

What allergen-specific approaches are being investigated?

In addition to the approval of peanut allergen powder for the treatment of peanut allergy for patients aged 4–17 years, various other oral immunotherapies (OITs) are currently being investigated (Figure 1, Table 1)38.

T4 Food Allergy_Fig1.png

Figure 1. Mechanisms of food allergy and investigational immunotherapy treatments (Adapted40). EPIT, epicutaneous immunotherapy; H1/2, histamine; IgE, immunoglobulin E; IgG, immunoglobulin G; IL, interleukin; ILC2, type 2 innate lymphoid cells; IT, immunotherapy; OIT, oral immunotherapy; PAMPs, pathogen-associated molecular patterns; SLIT, sublingual immunotherapy; TH2, T helper 2 cell; Treg, regulatory T cells; TSLP, thymic stromal lymphopoietin.

Other routes of exposure are also currently being investigated, including under the tongue with sublingual immunotherapies (SLITs) and through the skin with epicutaneous immunotherapies (EPITs), individually and in combination38.

OIT, SLIT, and EPIT are allergen-specific approaches utilising the progressive increase of exposure to a specific food allergen with the goal of reaching a daily maintenance dose to achieve desensitisation41,42.

Repeated exposure to the antigen through immunotherapy is believed to induce or restore tolerance to the allergen through decreased activation of mast cells and basophils due to decreased circulating immunoglobulin E (IgE), increased allergen-specific immunoglobulin G4 (IgG4)antibodies, and decreased T helper type 2 (TH2) cells43.

A comprehensive systematic review and meta-analysis (N=1,259), the efficacy and safety of OIT, SLIT, and EPIT management in food allergy were assessed44. In the twenty-seven trials included, they revealed a substantial benefit of OIT and SLIT compared to controls with respect to desensitisation (risk ratio [RR]=0.16, 95% CI 0.10, 0.26; Test for overall effect: Z=−7.582 [P<0.0001]). Eight studies also suggested a benefit to sustained unresponsiveness; however, this was not confirmed (RR=0.29, 95% CI 0.08, 1.13; Test for overall effect: Z=−1.788 [P<0.074])44.

Table 1 contains a non-exhaustive selection of published clinical studies in peanut allergy. In addition to these studies, other food allergens and methods of immunotherapy are actively being studied, including multi-allergen oral immunotherapy studies38.

Table 1. Overview of 2015 – 2021 published clinical studies, with DBPCFC inclusion criteria (Adapted45–47). DBPC, double blind placebo controlled; DBPCFC, double blind placebo controlled food challenge; EPIT, epicutaneous immunotherapy; M, months; OFC, oral food challenge; OIT, oral immunotherapy; PbO, placebo; pOIT, peanut oral immunotherapy; PP, peanut protein; ppOIT, peanut OIT plus probiotics; RCT, randomised controlled trial; SLIT sublingual immunotherapy; W, weeks.

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