Selecting patients for food allergy therapy

Abstract

Background:

Food allergies pose a significant burden on the daily life of individuals with food allergy, including dietary, psychosocial, and economic impact. The management of food allergy has shifted recently from previous passive avoidance approaches to current active therapeutic interventions.

Objective:

This article aims to discuss selection of patients with food allergies for different therapies.

Methods:

Published literature on risks and benefits of various therapies as well as articles on shared decision-making were reviewed for this article. Key papers are included.

Results and Conclusion:

In addition to the two U.S. Food and Drug Administration approved therapies currently available (for oral peanut immunotherapy and for treatment of single and/or multiple food allergies), many novel treatments are on the horizon. Alternative forms of food immunotherapy, such as epicutaneous and sublingual, as well as a variety of new biologics are under development. When selecting patients for therapy, it is important to consider multiple factors, including eligibility, age, type of food, history of life-threatening reactions, baseline quality of life, and the presence of atopic comorbidities. As the food allergy landscape becomes enriched with novel treatment modalities, choice of the appropriate therapy for each individual is more challenging. Avoidance also remains an acceptable strategy for those who prefer this approach.

Food allergies affect an estimated 8% of children and 10% of adults in the United States.^1,2 They can impact the lives of patients in multiple ways, including social interactions, dietary limitations and nutritional effects, psychological burden (such as fear of accidental exposures, bullying), and cost.^3–5 Food allergy is also a wider health-care and societal issue, with increasing prevalence,⁶ health-care utilization, and economic costs (both direct and indirect).^7,8 For many years, the only available approach consisted of avoiding the allergenic food(s), but, in the past few years, active approaches for managing food allergies have also emerged. These include two currently U.S. Food and Drug Administration (FDA) approved products and/or drugs as well as many treatments in various stages across the development pipeline.^9,10

To successfully select an appropriate therapy, it is important to know which therapies are currently available and what practical requirements are there for each one, in addition to benefits and risks of treatment. The first food allergy therapy approved by the FDA in 2020 was a drug licensed for peanut oral immunotherapy (OIT).⁹ The drug was initially licensed for ages 4–17 years, but the license was recently extended to also cover ages 1–3 years. It is not licensed currently for adults. OIT involves the administration of increasingly large daily doses of the allergenic foods.¹¹ Dose increases typically occur in the clinic to ensure that the dose is tolerated. In between the clinic updosing visits, the patient takes the tolerated dose at home.¹¹ The aim is to reach a target maintenance dose that will protect individuals from accidental exposures and severe allergic reactions. Rates of desensitization are ∼60–80% after a year of therapy.^11,12 Limitations of this therapy include allergic reactions during treatment, which are mostly mild-moderate, but anaphylaxis may also occur in ∼10–20%.^11,13 There is a need to reduce or transiently stop therapy during periods of illness and/or tiredness and/or sleep deprivation or menstruation. In addition, exercise and, for some patients, hot showers are not allowed within 2–3 hours after dosing.¹⁴ Taste aversion related to the food allergen ingested has also been observed.¹⁵ Uncontrolled asthma is a contraindication in initiating OIT.^11,16 Of note, noncommercial OIT is also practiced in a variety of settings.¹⁶ The second FDA-approved product is omalizumab, licensed in 2024 for treating both single and multiple food allergies, in individuals ages ≥ 1 year.¹⁰ Omalizumab is administered in the form of a subcutaneous injection, every 2–4 weeks, depending on weight and total serum immunoglobulin E (IgE) level at baseline (pretreatment). Injection-site reactions are common, but anaphylaxis related to the drug is very rare.¹⁷ Neither of the two drugs is a cure for food allergy, but both aim to increase the threshold of reactivity and provide protection from allergen exposures.

When considering therapeutic approaches, it is important to remember that participation in research trials that investigate new therapies can be another option. Alternative forms of immunotherapy such as epicutaneous and sublingual are being studied, and show good efficacy and safety, especially with longer treatment duration.^18,19 Epicutaneous immunotherapy (EPIT) involves the application of a patch on the skin (usually on the patient’s back) that contains 250 μg of peanut protein.¹⁸ The protein is slowly absorbed through the skin, which results in desensitization. After a 12-month period, research studies showed an efficacy rate of 35.3% in increasing the eliciting dose and achieving desensitization.¹⁸ EPIT uses a proprietary patch that is not available as yet for use outside the research setting. Sublingual immunotherapy consists of the administration of daily liquid drops, which contain a few milligrams of protein (e.g., 2–4 mg of peanut protein), under the tongue. Rates of desensitization after 44 weeks are reported as 70%.¹⁹ Sublingual immunotherapy is being reported in clinical use as well.²⁰ Unfortunately, there is very little homogeneity across trials in terms of populations enrolled, target dose, and dosing schedules, which prevents a direct comparison among different immunotherapy routes. In addition to different immunotherapy forms, various biologics are also being investigated for use in food allergy. Recently published trials on the use of dupilumab in food allergy have shown limited efficacy despite the drug having a license for use in other atopic conditions, such as eosinophilic esophagitis, asthma, and atopic dermatitis (as well as sinusitis with nasal polyps, prurigo nodularis, and chronic obstructive pulmonary disease).²¹

Selecting patients for therapy can be a complex process, likely to become more complicated as new treatments come into the market (Fig. 1). First, the clinician needs to assess the patient for eligibility for each available therapy. There are certain contraindications as well as limitations that do not allow every patient to receive every therapy. For example, OIT is contraindicated in individuals with active eosinophilic esophagitis (for some, this is a relative contraindication).²² It is also contraindicated in patients noncompliant with epinephrine carriage and use.²² This limitation is due to safety concerns. However, omalizumab has a dosing guide for total serum IgE levels of up to 1850 IU/mL, so patients with higher total IgE values are currently not eligible.²³ Second, the process of “selection” has changed significantly over time because patients now have a key role in choosing options for their care. The physician is responsible for making the correct diagnosis of food allergy, informing patients of the available options, and describing what each of these option entails (including risks and benefits). The patient or caregiver, however, is responsible for sharing with his or her physician his or her goals for therapy as well as preferences with regard to different options and what matters most to him or her (his or her values). Selection, therefore, reflects a two-way conversation between the patient and the physician, exploring all approaches for therapy, and making a decision on the one that the patient values the most and aligns with his or her preferences and goals. This process is also known as shared decision-making.^24–26 Third, the age of the patient is a consideration. As noted above, the currently available products are licensed for different age groups. There is also ongoing discussion on the optimal time for intervention with a suggestion that early therapy (infants and toddlers up to age 4 years) is likely associated with a better efficacy and safety profile.^27–29 Real-world data, mostly from Canada, have shown good safety and efficacy of early life peanut OIT.^30,31 This practice has not yet been replicated in other countries, and there are limited data that support it currently, with a lack of head-to-head studies that focus on early versus late treatment. Fourth, the type and number of food(s) treated may also influence therapy selection. Certain food allergies, such as milk, egg, wheat, soy, will resolve in the majority of individuals by early adulthood, whereas others, such as peanut, tree nuts, seeds, and seafood, will likely persist lifelong.^32–37 There is, therefore, a perspective to be considered on whether waiting to see if the food allergy will resolve may be a consideration during shared decision-making. Fifth, baseline quality of life should be taken into consideration when discussing active interventions for food allergy. Most studies that focus on quality-of-life changes before and after OIT have shown improvement in quality of life, although this was not a universal finding, with some studies that showed that ultimate improvement occurred at maintenance and quality of life may actually decrease during the updosing period.^12,38–41 Similarly, limited research on quality-of-life changes before and after EPIT has shown improvement after treatment.⁴² For omalizumab, no change was noted in the initial trial period (blinded period of therapy), but improvement was shown during the trial extension period.¹⁷ Sixth, a number of other factors, including the presence of atopic comorbidities (asthma, allergic rhinitis, atopic dermatitis), a history of a life-threatening allergic reaction to trace amounts of food may influence therapy selection. For example, individuals with food allergy and with moderate-severe concomitant asthma may choose omalizumab because the drug has been used for many years to treat asthma. In contrast, OIT is not recommended when asthma is not well controlled.²² It is important to note that avoidance remains a valid option for individuals who prefer this approach, e.g., in patients with food allergy who do not experience reduced quality of life at baseline.

Figure 1.

Considerations when selecting patients for food allergy therapies.

Shared decision-making has center place in patient and therapy selection. With an increasing focus on value-based medicine and personalized care models, a number of patient-related factors need to be taken into account in this process. The cost of treatment is a significant one. This needs to take into account both direct costs (e.g., cost of drug, clinic visit, out of pocket), and indirect costs (e.g., travel, time off work). Very few studies have evaluated the cost-effectiveness of new therapies to date.^43,44 In addition, access to treatments and equity issues remain as unmet needs.⁴⁵

CONCLUSION

We are navigating an exciting landscape for food allergy therapy, with two already FDA-approved drugs and many more in different stages of development. As the landscape becomes enriched with novel treatment modalities, the choice of the appropriate therapy for each individual is more challenging. The use of shared decision-making facilitates this process and allows for the choice that best fits every patient, every time.