Recently there has been a great deal of interest in local and national media about how peanut allergic patients can overcome their allergy enabling them to eat peanuts without worry of reaction. Oral food desensitization is a potentially exciting and even liberating concept. But like many issues in health care, there are potential pros and cons that are being uncovered as studies go forward, including safety, cost, side effects, candidate foods, convenience, etc. that remain unclear or unanswered. This article details some of our findings on both sides of the issue to date.
What is the science of oral food immunotherapy? By way of background, 4-5% of the US population is allergic to foods and 1-3% are allergic to peanuts. The annual death from food anaphylaxis is estimated to be 150-200/year, 67% caused by peanuts. This represents 1 death per every 24,000 peanut allergic patients/year. Most people who die from peanuts knew they were allergic, and most did not have their epinephrine on hand. Other than death, 1.6% of peanut allergic persons have a severe reaction to accidental peanut exposure/year, and 1.1% of peanut allergic persons require epinephrine per year. Spontaneous loss of peanut allergy occurs in 4% of peanut allergic children each year, and cumulative remissions over 7-8 years is 22-34%
What is the status of clinical studies on peanut OIT to date? In this country we have a few select centers of excellence that are independently funded and equipped to conduct academically robust clinical trials to answer questions of peanut and other food allergy immunotherapy. While protocols vary somewhat from institution to institution, there are some general approaches that are part of these investigations. Protocols to study peanut oral immunotherapy generally include:
- A one day escalation phase (0.1 mg doubling every 30 minutes to a certain maximum, often 50 mg. For reference, one peanut contains about 180 to 200 mg of peanut protein allergen. During this phase, 50% or more develop significant and sometimes serious adverse events, and most experience a 10% dropout rate.
- A maintenance phase where over several months there is a step increase 25-50 mg every few weeks to achieve a daily maintenance dose, generally 1800 to 4,000 mg/day (9 to 20 peanuts). This phase is maintained variably for months to 3 years. During this time, 50% of patients experience adverse effects. Studies indicate that around 85% of study patients can achieve this dose on an ongoing basis.
- A challenge test on while on maintenance (usually 4000-5000 mg peanut protein) to demonstrate true tolerance to peanuts.
- A discontinuation phase where oral peanuts are stopped, and generally 2-3 months later patients undergo another oral challenge to determine if they remain truly desensitized. While studies vary, such oral challenges are associated with a 50-80% pass rate, but this seems to decline with additional time and subjects become susceptible again to serious reactions.
Adverse effects and complications may occur as a consequence of peanut OIT. In one study, 12% of peanut allergic patients required epinephrine during escalation phase, and 6% of patients during maintenance. Recently, there is concern about a rising prevalence of eosinophilic esophagitis (EoE) in oral peanut desensitized patients. EoE is a disorder of the food tube characterized by marked infiltration of a particular type of WBC (eosinophil) that can lead to pain, narrowing and chronic inflammation. The incidence in of EoE in the general population is 1/10,000, while the incidence in a peanut OIT study was 10% of patients given oral peanut immunotherapy. Other oral and GI side effects, wheezing, worsening asthma, anaphylaxis have been shown to worsen or evolve in some patients. Outcomes studies seem to indicate that peanut OIT does not lead to cure, and continuous exposure to peanuts is likely needed to sustain desensitization.
At the center of increasing interest in using peanut OIT in routine clinical practice is a recently published paper by Wasserman et al. This study consists of a retrospective chart review of 352 patients who underwent peanut OIT in 5 different practices. They found an 85% success in desensitization to peanut. Since this review was retrospective, the article has some flaws inherent in such studies. In general, selection criteria from different centers were not well defined, methods varied considerably from center to center, targeted maintenance doses varied from 415 to 8000 mg of peanut protein, and the maintenance period was variable. Reactions requiring epinephrine were required in 0.7 of 1000 doses during escalation, and 0.2 of 100 doses during maintenance. There was a 5% drop out rate of those on maintenance. While a helpful review, several problems were noted with the methods and outcomes, including an enormous range of maintenance dosing, patients on treatment were twice as likely to require epinephrine than untreated patients, no long term reduction in reactions from accidental exposures was determined, there was no data on less-severe reactions or reactions that required treatment with other medications or required ER visits, the risk of EoE in patients treated with peanut OIT was 10%, and cost date was not provided, although cost for peanut OIT compared to standard care requires frequent, time-consuming office visits as opposed to a yearly visit in those not on treatment
The outcomes of this and other studies looking at peanut OIT must be compared with the current standard of care for peanut allergy: accurate diagnosis, education about avoidance, self-injectable epinephrine. Compared with peanut OIT, current standard care has the following outcomes: incidence of fatal anaphylaxis = 134 deaths/year (vs unknown for peanut OIT), incidence of epinephrine treated reactions = 1.1%/year (vs several on peanut OIT), incidence of EoE is 0.0001%/year (vs 10% on peanut OIT), incidence of remission/cure is 4%/year (vs 85% on peanut OIT, at least for a period and probably declines), and cost is low (vs peanut OIT).
For these and other reasons, editorials and reviews of peanut OIT to date suggest that this method of treatment for peanut allergy is promising but at this point is not the treatment method of choice. A few such articles and opinions include:
- Wood and Sampson (JACI January 2014): “We remain convinced that food OIT is not ready for clinical practice”
- Sampson, Peanut oral immunotherapy: Is it ready for clinical practice? (JACI In Practice, 2013): “Although peanut oral immunotherapy shows promise, the evidence currently available on its effectiveness, risk benefit, and potential long-term consequences is insufficient to support its use in clinical practice. Appropriately designed, prospective clinical trials are urgently needed to determine whether oral immunotherapy is a safe, effective form of therapy for food allergy.”
- Nurmatov et al: Cochrane Database Review 2012: “Peanut OIT represents a promising, potentially disease-modifying therapeutic approach for the management of IgE-mediated peanut allergy. However, currently there is insufficient evidence in terms of long-term effectiveness, safety, and cost-effectiveness of peanut OIT to recommend its routine use in clinical practice.”
- Cox et al (JACI 2011, AIT practice parameter): “The safety and efficacy of oral and sublingual immunotherapy for food hypersensitivity is currently investigational.”
We encourage patients to speak with their allergy doctor certified by the American Board of Allergy and Immunology and discuss what may be the best approach for them and their family members regarding peanut allergy.