Oral Desensitization for Peanut Allergy: Is It Why No, Or Is It Why Not?

posted in Food Allergy

Over the 25 years of treating patients with allergic conditions, I have witnessed changes in the prevalence, prevention advice and treatment of peanut allergy. The prevalence of peanut allergy in children in the United States, based on self-reporting in random telephone surveys, has increased from 0.4% in 1997 to 0.8% in 2002 to 1.4% in 2008.  In 2000, the recommendation from experts was for the child to avoid eating peanut until 3 years old. Now, the recommendation based on the LEAP and EAT clinical trials is to introduce peanut at some time between age 3 to 6 months old.

Peanut oral desensitization, also known as oral immunotherapy or OIT, has received increasing attention since the first case reports of its success in 2006 and the first clinical trial in 2009. The amount of peanut protein that can be eaten safely with OIT has been reported in studies to be as high as 1000 mg (approximately 4 peanut kernels) to 5000 mg (approximately 20 peanut kernels).

The percentage of peanut-allergic patients who are considered to develop a form of tolerance, called sustained unresponsiveness, after completing the treatment protocols of these clinical trials ranges widely—depending on the design and analysis of the trial– from 31% to 78%. These studies suggest, so far, that sustained unresponsiveness may be more likely to occur in younger children or those with relatively less positive baseline peanut skin tests and peanut blood tests.

No therapy, though, is without requirements and risk. The most notable of these are the following:

-The dose of peanut protein must be eaten at least once a day and every day.

-As with airborne allergen injection immunotherapy, there is a build-up phase and a maintenance phase.

-Based on a published protocol from a community-based group of allergists in Dallas, the build-up phase is 21 weeks of weekly office visits. The 1st week office visit is about a five-hour day of giving orally every 20-30 minutes a total of ten low doses of peanut protein—starting at microgram amounts— in the form of peanut flour diluted in distilled water flavored with Kool-Aid.  Subsequent weekly visits are approximately one hour for the single dose increase.  The dose of peanut tolerated in the office then becomes the dose that must be eaten every day.

-Before the daily dose consists of peanut kernels, the daily dose comes from diluted peanut flour in glass jars that are prepared in the allergist’s office, and then from peanut flour in capsules prepared at a specialty pharmacy.

-The maintenance phase in this protocol lasts for 3 years. After a one month follow-up office visit, office visits are then every 6 months.

-Serious allergic reactions that require the use of epinephrine can occur in a number of patients. Five community-based allergy practices that published their peanut OIT experience with a total of 352 patients found that 55 (15%) required epinephrine for treatment of reactions.

-The risk factors for serious reactions include the following:

  • Eating the peanut dose on an empty stomach
  • Exercising immediately prior to or within 2 hours after eating peanut, which I have seen so far.
  • An illness with a fever or an episode of gastroenteritis
  • Uncontrolled asthma, nasal/sinus allergies or eczema

-Modification of some daily activities must correspondingly be made in order to reduce these risk factors.

Peanut OIT is not widely and routinely used at this time because of concerns raised by food allergy researchers. These concerns include a reaction rate that is not negligible and can require epinephrine for stopping the reaction, an optimal maintenance dose that is not well-defined and an uncertain duration of the maintenance phase.  Avoidance of the food, which is the current standard of care, is still recommended by them.

Are there other current options and future possibilities? Sublingual desensitization (SLIT), in which the food is placed under the tongue and absorbed from there, has been studied for peanut and used by some community-based allergists.  In a 2015 study of 21 peanut-allergic patients randomized to either SLIT or OIT, adverse effects were substantially less for those who received SLIT.  However, patients who received OIT tolerated an average of approximately 24 peanuts, whereas patients who received SLIT tolerated an average of 1 to 2 peanuts.

Two other commercial products are in phase 3 clinical trials. Phase 3 is the last stage of experimental data that researchers must submit to the Food and Drug Administration (FDA), who then decides whether the product should be approved to market and for what purpose.

One of these products is a patch called Viaskin Peanut. A new patch containing up to 250 micrograms of peanut protein is placed daily on either the back or the upper arm.  Patients in the phase 2 clinical trial tolerated up to a median amount of 130 mg (less than 1 peanut) of peanut protein per day.  Side effects have not included anaphylaxis, but have included redness and a few bumps at the site of the actual peanut patch in 23% of those individuals.  The other product is oral desensitization with pharmaceutical grade peanut protein in a capsule—called AR101 for now.  The phase 2 study of 23 patients showed that all tolerated a cumulative amount of 443 mg (approximately 1½ peanuts) of peanut protein and that 18 of 23 tolerated a cumulative amount of 1,043 mg (approximately 4 peanuts) of peanut protein.

The title of this blog was motivated by the George Bernard Shaw quote: “You see things and you say ‘Why?’ But I dream things that never were and I say ‘Why not?”  The decision to go beyond avoidance and commit to oral desensitization is not straightforward.  Only the parents who see how their child is affected by peanut allergy can decide—after weighing both the process and the expected degree of protection—how to best provide comfort and the opportunity to thrive.

Dr. Klein