Oral Immunotherapy: The Answer to Peanut Allergy?

Peanut-allergen powder approved by the FDA for the treatment of childhood peanut allergy

Young boy is tested for allergens

By Rachel M WhitselAPRN; Jaclyn A BjelacMD; Ahila SubramanianMD; Alice EW Hoyt, MD; and Sandra J HongMD

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Please note: This is an abridged version of an article that originally appeared in the Cleveland Clinic Journal of Medicine. To view it in its entirety, including a complete list of references, please visit https://www.ccjm.org/content/88/2/104.

Food allergies affect 32 million Americans, including roughly one in 13 children or two in every average-size American classroom.1,2 In a recent survey,3 approximately 38% of 4,075 respondents, both children and adults, reported having at least 1 food-related allergic reaction per year.

Peanut and tree-nut allergies have increased dramatically in prevalence, especially in children. Historically, children with food allergies have been treated through strict avoidance of the allergen. Recently, an oral preparation of peanut allergen (Palforzia) was approved for immunotherapy (ie, desensitization) in children 4 to 17 years old. This article reviews oral immunotherapy and its role in children with peanut allergies.

Peanut allergy

Many food allergies are first diagnosed when the patient is a young child. The most common food allergy in children is peanut and tree-nut allergy, estimated to affect 1 million children, and its prevalence more than tripled between 1997 and 2008.4 Peanut allergy is also the most common cause of severe food-associated anaphylaxis.

Risk factors for peanut allergy include severe atopic dermatitis, egg allergy in infancy, a family history of peanut allergy, and a personal or family history of atopy.5,6 The higher risk of familial peanut allergy may be in part related to delayed and reluctant introduction of peanuts to siblings of peanut-allergic children. Recent research suggests that delayed introduction of peanut into the diet is linked to higher rates of peanut allergies.4,7 The Learning Early About Peanut Allergy trial showed that introducing peanuts to children at age 4 to 11 months decreased the risk of developing a peanut allergy in children at high risk.8 Once patients develop peanut allergy, only 20% to 25% develop tolerance; most maintain their allergy for life.9

A new treatment option

Treatment of peanut allergy has been largely limited to educating patients and families about ingredient labeling and recommending complete avoidance of peanuts. Anaphylaxis caused by exposure to an allergen requires immediate treatment with epinephrine.

Oral immunotherapy is an emerging option offered by a limited number of allergists and immunologists. Although this therapy has shown some efficacy for food allergy desensitization, it has been criticized for lacking established protocols, having high rates of adverse reactions, and using grocery store products that may contain variable amounts of the allergenic proteins.10,11

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In January 2020, the US Food and Drug Administration (FDA) approved a novel peanut-derived oral immunotherapy product for treating childhood peanut allergy: Palforzia (peanut Arachis hypogaea allergen powder-dnfp). Containing a powder derived from roasted peanuts packaged in capsules or sachets at varying doses, it is indicated for use in children 4 to 17 years old. The capsule or sachet is not swallowed. Instead, it is opened, and the powder is mixed with applesauce, pudding, or something similar. It is given in dosing phases according to an oral immunotherapy protocol.

Efficacy and safety

Safety and efficacy data for the peanut-allergen agent come from clinical trials that enrolled more than 700 patients who were allergic to peanuts.

In a phase 3 trial,16 551 patients ages 4 to 55 with allergic dose-limiting symptoms at 100 mg or less of peanut protein (approximately one-third of a peanut kernel) were randomly assigned to receive the study drug or placebo in an escalating-dose protocol. Most patients (n = 496) were between ages 4 and 17, which reflects the FDA-approved age range.

Once participants reached the final study dose, they underwent a peanut challenge. The study drug recipients could ingest higher doses of peanut protein without dose-limiting symptoms than placebo recipients. The most common adverse reactions during treatment (incidence > 5%) were gastrointestinal, respiratory, and skin symptoms and anaphylactic reactions.16

This peanut-derived oral immunotherapy agent, like other forms of oral immunotherapy (which are not FDA-approved), is not appropriate for patients with uncontrolled asthma, eosinophilic esophagitis or other eosinophilic gastrointestinal disease.

Adverse reactions are a leading reason for stopping oral immunotherapy. In the randomized controlled trial of peanut allergen,16 43 (11.6%) of the 362 patients assigned to the active treatment group withdrew because of adverse events. Gastrointestinal disorders accounted for most of the adverse reaction-related discontinuations. Most discontinuations occur during the escalation or up-dosing phases, with only a few patients withdrawing during the maintenance phase.15,16

For those experiencing adverse reactions, the onset was typically rapid (median time 4 minutes after the dose), and symptoms resolved relatively quickly (median time 37 minutes).15 Thus, careful patient monitoring is crucial during the first hour after dosing. Additionally, dose escalation and up-dosing must be done in a medical setting with medical personnel experienced with oral immunotherapy and treatment of allergic reactions.

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Patients should be cautioned that the FDA-approved oral immunotherapy product is not a cure for food allergies; instead, it is intended to reduce their reactivity to peanut. In the initial clinical trials, an exit challenge was included to approximate a real-life scenario of accidental ingestion.

Daily dosing important

Longitudinal studies are under way, with two-year data from an open-label follow-up study that suggest long-term efficacy of daily treatment with the peanut-derived oral immunotherapy agent.17 Patients who received daily doses in the study showed greater immunomodulation and higher rates of desensitization that increased over time compared with patients given nondaily dosing. Furthermore, most patients in the daily-dosing groups had lower adverse event rates than those in the nondaily dosing groups.

All forms of oral immunotherapy carry the risk of life-threatening anaphylaxis. Oral immunotherapy has not been studied in pregnant women, and the risks to a fetus are unknown. Anaphylactic reactions could lead to hypotension and potential fetal demise.

Counseling needed

Patients and families must be carefully counseled on the signs and symptoms of anaphylaxis and carry auto-injectable epinephrine at all times. Strict avoidance of allergens, aside from daily oral immunotherapy dosing, is imperative. Illness, physical exertion around dosing, and recent dental work or tooth loss may increase the risk of a reaction.

When identifying candidates for oral immunotherapy, consideration should be given to the capacity of the patient and family to adhere to the safety precautions and dosing regimens. This requires careful discussion of medication compliance, family support, and ability to attend regularly scheduled appointments before initiating treatment. Patients with families who are not highly motivated to incorporate the necessary lifestyle modifications are unlikely to be ideal candidates for therapy.