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Management of Peanut Allergy: A Focus on Novel Immunotherapies

Christopher P. Parrish, MD
The management of peanut allergy involves strict avoidance, prompt recognition of allergic reactions, and rapid initiation of epinephrine and other supportive therapy for anaphylaxis. Avoidance presents several challenges and burdens to quality of life and daily activities. Currently, no treatment options are available for peanut allergy apart from epinephrine, which is the treatment of choice for severe allergic reactions. In recognition of the need for improved treatment options among patients with peanut allergy, several novel immunotherapies are undergoing clinical development, and clinicians must be knowledgeable about the safety and efficacy of these agents. This educational activity will provide an overview of current practices in peanut allergy management and novel immunotherapies with potential to improve outcomes among children and adults with peanut allergy.
Am J Manag Care. 2018;24:-S0
Because even a small amount of allergen can induce a systemic reaction in an individual with peanut allergy, strict avoidance is necessary to prevent life-threatening complications.1 However, effective avoidance presents several challenges to patients and their families, leading to substantial burdens to quality of life and daily activities.2,3 For example, Avery et al found that children with peanut allergy felt more threatened by potential hazards within their environment, more restricted regarding physical activity, and more worried about being away from home than did children with insulin-dependent diabetes.2 Alongside children’s burdens, parents also report significant disruption of daily activities due to avoidance measures.4,5 When dining out, adults with peanut allergy have reported social embarrassment from the need to check whether a particular food contains peanuts, and wanting to avoid this embarrassment can lead to increased risk-taking behaviors.3 Additionally, the need to seek familiarity in choice of establishment to reduce anxiety led to a lack of spontaneity in daily living, which was a regret for some adults with peanut allergy.3 While traveling, research has shown that peanut exposures can and do commonly occur on commercial airline flights, leaving many individuals with the responsibility of cleaning their own seats and not consuming any food served onboard.6 Approximately 1 of 8 people with peanut allergy have reported no longer flying due to fear of exposure while onboard an airplane,6 and these fears are not unwarranted. Close to half of fatal food allergy reactions are triggered by food consumed away from the home, and most reactions occur from foods not thought to contain the allergen.7

In addition to venturing outside home, strict avoidance must be maintained within the home. Although common household cleaning supplies will reliably remove peanut allergens from tabletops, dishwashing liquid alone will not.8 Similarly, hand soap and commercial wipes will remove peanut allergen from skin, but antibacterial hand sanitizer will not.8 When preparing food in the home, individuals and parents of children with peanut allergy must be careful not to cross-contaminate preparations and must carefully check food labels for allergens. The Food Allergen Labeling and Consumer Protection Act of 2004 requires that all food labels clearly identify the food source names of all ingredients that are or contain any protein derived from the 8 most common allergens, which are milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat, and soybeans.9

Regardless of labeling mandates, cross-contamination within the manufacturing setting is still a risk, and the disclosure of this risk on labeling remains voluntary.9 The wording of these precautionary labels is not standardized (“may contain [allergen],” “manufactured on shared equipment with [allergen],” “manufactured in the same facility with [allergen],” etc), yet studies have shown that individuals often ascribe a differing amount of risk based on the wording used.10 Managed care professionals should be aware of  potential misconceptions about avoidance and food labels as well as common myths and key messages, as shown in Table 1.10

Although avoidance is necessary to minimize the risk of exposure to an antigen, it is difficult to accomplish in day-to-day life, and severe reactions frequently occur despite significant efforts.11 Several challenges must be overcome to achieve effective avoidance, including understanding food labels, overcoming embarrassment (adults) and potential bullying (children) in social situations, failing to recognize actual risk, and preventing cross-contamination in the home. These issues should routinely be addressed in clinical practice with patients who have peanut allergy, and with their families.

Anaphylaxis

Anaphylaxis is a life-threatening emergency requiring immediate intervention.12 Although death is rare, it can occur and has occurred despite immediate epinephrine (adrenaline) use. Guidelines from the World Allergy Organization (WAO) recommend epinephrine as first-line treatment for anaphylaxis.13 Epinephrine has 3 primary mechanisms of action in anaphylaxis: (1) alpha-1 agonist vasoconstrictor effects prevent and relieve airway edema, hypotension, and shock; (2) β-1 agonist chronotropic and inotropic effects increase the rate and force of cardiac contractions; and (3) β-2 agonist effects lead to bronchodilation and decreased mediator release.13 Epinephrine is the only agent that has been shown to decrease hospitalizations and death in individuals experiencing an anaphylactic reaction.13 Usually administered through an epinephrine autoinjector, early injection of epinephrine (ie, before arrival to the emergency department [ED]), has been shown to reduce the odds of hospitalization compared with late administration (odds ratio [OR], 0.25; 95% CI, 0.12-0.49).14 Most importantly, delay in epinephrine administration has been associated with food allergy-induced fatalities.12

The use of an epinephrine autoinjector has been associated with fewer adverse events (AEs) compared with intravenous (IV) bolus administration of epinephrine.15 An observational study by Campbell et al evaluated outcomes between routes of epinephrine administration in an ED setting.15 Of 573 patients, 4 overdoses occurred, all with patients who received IV bolus epinephrine. Furthermore, cardiovascular AEs were seen in 10.0% of patients receiving IV bolus epinephrine compared with just 1.3% of patients using an epinephrine autoinjector (OR, 8.7; 95% CI, 1.8-40.7; = .006).15 Therefore, extreme caution is recommended when using IV bolus epinephrine.13

For adults, the dosage of epinephrine for anaphylaxis is 0.2 to 0.5 mg (0.2 to 0.5 mL of 1 mg/mL solution) intramuscularly (IM) or subcutaneously (SC) every 5 minutes as needed.16 For IV administration, the dose is 1 mg (1 mL of 1 mg/mL solution) in 250 mL of dextrose sodium chloride (4 mcg/mL) infused at 1 mcg/min (15 mL/h) or 1 mg in 100 mL of normal saline (10 mcg/mL) infused at 5 to 15 mcg/min (30 to 100 mL/h).16 In children, the dose is 0.01 mg/kg (0.01 mL/kg of 1 mg/mL solution) or 0.3 mg/m2 SC to a maximum dose of 0.5 mL, which can be repeated every 4 hours if required.16 Epinephrine autoinjectors are available in 0.1-, 0.15-, and 0.3-mg doses and may be injected SC or IM; doses may be repeated if severe anaphylaxis persists.16 This is a summary of dosages, and full dosing guidelines should be reviewed for complete recommendations.

The correct use of epinephrine autoinjectors is a critical aspect in the management of care for patients with allergies. Bonds et al found that among 102 patients using epinephrine autoinjectors, just 16% administered the epinephrine correctly; of the remaining 84%, 56% missed 3 or more steps in the administration process.17 Errors included not holding the unit in place for 10 seconds after triggering (76% made this mistake), failure to place the needle end of the device on the thigh, and failure to depress the device forcefully enough to activate the injection.17 When counseling on the use of epinephrine autoinjectors, managed care professionals should ensure that the patient and/or caregiver is aware of potential AEs (eg, palpitations, pale skin, sweating, nausea, vomiting, asthenia, dizziness, headache, tremor, and anxiety), how to recognize injection-site infections, and the importance of holding the leg of young children firmly during injection to prevent injury.16 Patients and caregivers should be advised to seek medical assistance after use, even if symptoms have subsided.16

Along with ensuring the proper administration technique, proper storage of epinephrine autoinjectors is also essential. Injectors should be kept at 20° C to 25° C (68° F-77° F) to protect the epinephrine from degradation; freezing for a few days is acceptable, although the solution must be thawed completely before use.13

Second- and third-line therapies for anaphylaxis include H1-antihistamines, H2-antihistamines, and glucocorticoids.13 It is important to understand that none of these agents should be used alone for anaphylaxis because these therapies are primarily prophylactic and supportive and are not lifesaving.13 Following an anaphylactic reaction, patients should be referred to an allergy/immunology specialist to accurately diagnose the trigger and provide long-term management.13

Emerging Therapies

There are a number of therapies currently under investigation for desensitization of peanut protein. To best understand the clinical data regarding the safety and efficacy of these agents, knowledge of best practice guidelines and common terminology is essential. These standards are summarized below, followed by an overview of the agents currently undergoing development for use in patients with peanut allergy.

PRACTALL Food Challenge Recommendations for Clinical Trials

When evaluating clinical trials involving patients with peanut allergy, managed care professionals should be aware of study design methodology and outcome definitions. Published in 2012 by the American Academy of Allergy, Asthma & Immunology (AAAAI) and European Academy of Allergy and Clinical Immunology (EAACI), the PRACTALL guidelines provide standardized recommendations for the performance of double-blind, placebo-controlled food challenges (DBPCFCs), which are considered the gold standard.18 Although some trials have successfully incorporated DBPCFCs into their methods, others have not, and recognition of these differences is important to interpreting outcomes.

 
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