Treating food allergy

Gain a deeper understanding of the management of food allergy with Professor Sharon Chinthrajah below, including the teams involved in allergy care, the importance of education, and oral immunotherapy (OIT).

What is the multidisciplinary approach to treating food allergy?

The optimal approach to food allergy management is multidisciplinary and multifaceted, providing care for the range of comorbid conditions associated with food allergy as well as guidance and education for patients and their carers (Figure 1)³. Care should be guided by a range of healthcare professionals, including³:

• General practitioners
• Allergists
• Dieticians
• Nurses
• Pharmacists
• Psychologists
• Dermatologists
• Pulmonologists

A close collaboration between gastroenterologists and allergists is also useful for the management of gastrointestinal (GI) abnormalities associated with food allergy, such as eosinophilic esophagitis (EoE)⁴. Moreover, previous studies have shown that OIT induces concerning GI symptoms in 75–85% of patients^5,6. There is also concern that OIT is inducing de novo EoE, which occurs in 2.7–4.7% of with IgE-mediated food allergy^7,8. However, recent research indicates that transient eosinophilic inflammation can occur during OIT, but does not necessarily induce pathological EoE⁹.

Figure 1. Current strategies for the management of food allergy^10,11.

Food allergies can also have a huge psychosocial impact due to anxiety that can be faced when eating in social environments. Psychologists and therapists are therefore essential for addressing the impact on quality of life and psychological distress associated with food allergy¹².

How do you provide education and dietary advice?

Dieticians play a key role in food allergy management by providing advice on allergen avoidance while also ensuring a balanced overall diet using replacement foods that replace all the nutrients required for a healthy diet. Trained in food allergy, they play a crucial role linking the clinical setting and community by guiding¹²:

• Practical dietary management
• How to read food labels
• Avoidance of foods with practical advice
• The substitution of foods
• Regular food challenges to assess tolerance

As part of the multidisciplinary group, nurses are also instrumental in educating patients on how to use medications such as adrenaline autoinjectors, inhalers, and nasal spray devices. This is especially important in cases of acute allergic reaction, when it is important to have prior knowledge on how to rapidly and effectively use adrenaline autoinjectors¹².

Active management

The risk of atopic disease in infants with a both parents, a single parent, or a sibling with a history of atopy is 40–60%¹³. Therefore, the ideal management of food allergy is through primary prevention¹³.

Over the last two decades advances in the prevention of food allergy have resulted in significant changes to infant feeding guidance¹⁴.

A milestone piece of research was the Learning Early About Peanut Allergy (LEAP) study, which assessed the effect of early peanut consumption on the risk of developing peanut allergy (N=640)¹⁵.

The LEAP study revealed that the prevalence of peanut allergy is lower following the early introduction of peanut¹⁵

LEAP showed that in children with an initial negative skin prick test at age 4–11 months, the prevalence of peanut allergy at 5 years of age was higher in the avoidance group than in the group that received an early introduction of peanut (13.7% vs 1.9%; P<0.001). Similarly, in children with a positive skin prick test at age 4–11 months, the prevalence of peanut allergy at 5 years was higher in the avoidance group than in the intervention group (35.3% vs 10.6%; P=0.004). When the positive and negative skin prick test groups were combined, prevalence was 3.2% in the intervention group and 17.2% in the avoidance group (P<0.0001, Figure 2)¹⁵.

The Enquiring About Tolerance (EAT) study recruited 1,303 infants aged 3 months who had been exclusively breastfed. The infants were randomised to either early introduction of six allergenic foods (cooked egg, peanut, cow’s milk, sesame, whitefish and wheat) or standard introduction recommended in the UK (exclusive breastfeeding to 6 months)¹⁶. The early introduction intervention was considered safe but not easily achieved and adherence to the study protocol was low (43%). The intention-to-treat analysis at 3 years of age found no significant difference between the two groups in the prevalence of allergy to one or more of the six foods (7.1% for standard introduction vs 5.6 for early introduction; P=0.32)¹⁶. Prevalence of peanut allergy at 3 years was 2.5% in the standard introduction group and 1.2% in the early introduction group but the difference was not statistically significant (P=0.11; Figure 2)¹⁶.

A subsequent analysis of the EAT study found that among infants with sensitisation to one or more foods, infants with early introduction developed significantly less food allergy to one or more foods than infants with standard introduction (34.2% vs 19.2%; P=0.03)¹⁷.

Figure 2. Prevalence of peanut allergies in in the LEAP¹⁵ and EAT^16,17 studies. Prevalence was determined in children aged 3 years in the EAT study and 5 years in the LEAP study. EAT, Enquiring About Tolerance; LEAP, Learning Early About Peanut Allergy.

These results paved the way for implementation of the dual exposure hypothesis that both oral and cutaneous exposure to allergens will ultimately result in tolerance to the particular allergen and, in the case of the LEAP study, peanuts (Figure 3)^18,19.

Figure 3. Dual exposure hypothesis to food allergens. GI, gastrointestinal; IFN, interferon; IL, interleukin; TGF, transforming growth factor; Th, T helper; Treg, regulatory T cells (Adapted ¹⁹).

The importance of moving away from food allergen avoidance towards active management

Dr Sharon Chinthrajah briefly explains the importance of moving away from avoidance of allergens to active management, which includes oral immunotherapy and biologics.

Is food allergy care the same for all ages?

The provision of support as patients switch to adult-centred care is essential as adolescence, between 11 and 25 years old, is an important period of development involving significant biological, psychological and social changes²⁰.

Transition is the process that addresses the medical, psychosocial, and educational needs of young people as they move from child to adult-centred care²⁰.

As adolescents progress to adulthood, they face considerable biological, psychological, and social changes, while becoming responsible for their own²¹

In a systematic review of 106 studies, a wide range of fixed and modifiable factors were found to influence the management of adolescents with allergies. These factors included²²:

• New life developments
• Psychological factors
• Risk-taking behaviours
• Supportive relationships

Given the complexity of challenges faced by younger patients, a steady transition from paediatric to adult medical care informed by multidisciplinary guidelines is essential²¹.

What are the immunotherapy approaches to food allergy?

Food immunotherapy involves the incremental administration of specific allergens at fixed or increasing doses with the goal of increasing the clinical reaction threshold. Various types of strategies have been investigated including oral, epicutaneous, and sublingual. However, peanut oral immunotherapy has been the most extensively studied²⁵.

What is oral immunotherapy (OIT)?

How important is it to understand the combination of biologics therapies with oral immunotherapies for future food allergy management?

Dr Sharon Chinthrajah discusses the importance of further understanding the combination of anti-IgE therapies (such as omalizumab and dupilumab), with oral immunotherapies in the treatment of food allergies.

OIT involves the ingestion of food allergen protein to induce clinical desensitisation. While OIT for many allergens have been investigated, clinical trials have primarily focused on peanut allergy. This led to peanut allergen powder becoming the first approved treatment, by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), for the prevention of severe reaction to peanuts in 4–17-year-olds^26,27.

A notable recent study on OIT was the POISED study (N=120), a Phase 2 randomised control trial that evaluated the long-term sustained effects of peanut allergy OIT in adults and children⁵.

The POISED study revealed that, most patients could be successfully desensitised to 4000 mg of peanut protein, however, discontinuation or reduction of peanut OIT could increase the chance of regaining clinical reactivity in the majority⁵

Patients were maintained on 4000 mg peanut protein through to week 104 and then separated into three groups:

• Peanut-0 group – discontinued peanut treatment
• Peanut-300 group – ingested 300 mg peanut protein daily for 52 weeks
• Placebo group – received oat flour

In the third year, using double-blind, placebo-controlled food challenges (DBPCFC) to 4000 mg peanut at three-month intervals up to one year, the primary outcome was met with 35% of the peanut-0 group and 4% of the placebo group passing the 4000 mg challenge at both 104 and 117 weeks (P=0.0024)⁵.

A significant difference between the Peanut-0 and Peanut-300 groups was observed with 13% of Peanut-0 versus 37% of Peanut-300 participants completing the 4000 mg DBPCFC 12 months after OIT discontinuation⁵.

The data in the POISED study highlighted that a discontinuation, or dose reduction, to 300 mg of peanut protein could lead to an increased chance of regaining a clinical reactivity to larger doses⁵. BATs and specific IgEs at baseline were able to identify those patients who were more likely to be successful at week 117²⁸.

Epicutaneous immunotherapy (EPIT)

EPIT requires placing an adhesive dermal patch, containing food protein, onto the skin to induce desensitisation through the passive transfer of solubilised protein via the skin²⁹.

A phase 2 multi-centre study (N=74) found that peanut EPIT administration was safe and produced a modest treatment response after 52 weeks, with the highest responses among younger children (4–11 vs >11 years, P=0.03)²⁹. Longer duration on therapy yielded larger tolerated doses on repeat challenges from the long term follow up of the Phase 3 study³⁰.

Sublingual immunotherapy (SLIT)

SLIT involves using drops or tablets to place small quantities of the allergen under the tongue to induce desensitisation³¹.

Various studies have determined the safety and efficacy of SLIT in hazelnut^32,33, peach³⁴, and peanut. A double-blind, placebo-controlled study, of peanut SLIT showed that SLIT safely induced clinical desensitisation in peanut allergic children, with the treatment group safely ingesting 20 times more peanut protein than the placebo group (median 1710 mg vs 85 mg, P=0.011)³¹.

What are the limitations of current management strategies?

While avoidance strategies and the newly approved oral immunotherapy (OIT) are recommended for the treatment of food allergy^1,2,23, it is important to consider their limitations when providing patient-centred care.

What are the limitations of allergen immunotherapy for food allergy?

While OIT is recommended in the European guidelines for the treatment of milk, egg, and peanut allergies²⁴, and peanut allergen powder is now approved for the prevention of severe reaction to peanuts²⁷, concerns have been raised about its safety³⁵.

Develop your knowledge of the limitations of OIT with Dr Sharon Chinthrajah below, such as their side effects and the possibility of severe reactions.

In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis (N=1,041), OIT versus no OIT was shown to increase:

• Anaphylaxis risk (risk ratio [RR] 3.12, P=0.0001)
• Anaphylaxis frequency (incidence rate ratio [IRR] 2.72, P=0.0004)
• Epinephrine use (RR 2.21, P=0.0048)

OIT also increased serious adverse events (RR 1.92, P=0.0488), and non-anaphylactic reactions (vomiting: RR 1.79, P<0.0001; angioedema: 2.25, P=0.021; upper tract respiratory reactions: 1.36, P=0.037; lower tract respiratory reactions: 1.55, P=0.071)³⁵.

Gastrointestinal symptoms are currently the most limiting side effect, affecting approximately 75–85% of people treated with OIT, preventing maintenance of treatment in some patients^5,6

Moreover, while systemic reactions are rare, additional severe reactions to OIT treatment include generalised urticaria/angioedema, wheezing/respiratory distress, laryngeal oedema, and repetitive emesis³³. Eosinophilic esophagitis (EoE) has also been shown to cause persistent abdominal symptoms in patients treated with OIT³⁶.

The risks of no therapy should be weighed against the benefits of successful treatment for each patient, using a shared decision making process based on patient preferences³⁷

Another important limitation to OIT treatment is the development of taste aversion over time. A long-term follow up for peanut OIT demonstrated that 10% of the patients discontinued treatment due to taste aversion and that patients with significant food aversion were more likely to discontinue treatment compared to patients who liked, or were indifferent to treatment (P=0.002)³⁸.

What are the limitations of avoidance?

For decades, the core strategy for treating food allergies has been strict avoidance backed up by an anaphylaxis action plan and carrying an epinephrine auto-injector^1,2.

However, while avoidance is useful for avoiding accidental exposure to food allergens, it can also be psychologically disabling³⁹. Over years of living with food allergies, patients can experience a range of psychological issues, such as depression, anxiety, and bullying³⁹.

In extreme cases, food avoidance can even lead to social isolation and high levels of anxiety focusing on the potential for future reactions³⁹.

Click here to learn more about the unmet needs of food allergy and the future of diagnosis and treatment