Considering Food Desensitization? Read This First

Editor's note: Originally published on January 25, 2019, this article has recently been updated.

We are on the cusp of a revolution in the management of food allergy, with a promising treatment now on the horizon.

The results of an industry-sponsored peanut oral immunotherapy (OIT) trial recently published in the New England Journal of Medicine^[1] have generated a lot of excitement. Impressively, it showed that in patients aged 4-17 years, 67.2% treated with the peanut-derived oral immunotherapy drug AR101 could tolerate 600 mg of peanut protein (about two whole peanuts) versus only 4% of controls. Nearly all patients who finished therapy could eat about 1.5 peanuts at the end, as long as they kept taking AR101. Almost 5% withdrew because of gastrointestinal (GI) side effects. Severe reactions occurred in about 5% of treated patients as well.

Comparatively, a recently published study^[2] of OIT in the private practice setting using peanut flour and other commercial peanut foods reported a higher rate of patient dropout (about 20%) and frequency of GI symptoms (37%). These authors reported that only 6.5% of patients achieved sustained unresponsiveness (defined as not reacting to peanut even a few months after stopping the study drug). Of patients with peanut-specific IgE levels >100, all were still reactive to peanut challenge.

Clearly, OIT is not curative. For most patients, it seems only to be protective for as long as they take it.

Limiting OIT Risks

A number of factors may trigger allergic reactions to the OIT dose, including nonsteroidal anti-inflammatory drug use, illness (upper respiratory or GI infection), stress/fatigue, seasonal allergy, and even consuming the OIT dose on an empty stomach.^[3]

This issue is highlighted by the case I heard about at a recent meeting, concerning OIT dose-related, exercise-induced anaphylaxis in an adolescent. The patient took her dose of OIT and then went to a track meet. After feeling unwell, she went to the bathroom, where she was soon discovered by friends to be swollen and vomiting. Had they not looked for her and called an ambulance, the results might have been worse. This speaks to the unwritten dangers of food allergy and OIT, especially in teenagers who have active schedules and may not appreciate the risks or consequences of ignoring medical advice.

Patient selection for OIT should, of course, only include patients actually allergic to the food. That necessitates food challenges because prior history alone is not predictive.^[4] As always, food challenges must be done cautiously. The symptoms-eliciting dose (threshold) for reactivity in peanut challenges ranges widely, from 25 mg (in 28%) to over 1 g (38%). It is important to note that the allergen content^[5] of peanut flours varies to some degree (about 20%), which probably raises the risk of OIT pending approval of AR101.

Other Emerging Treatments

It is estimated that OIT reduces the risk for accidental peanut allergy reactions by 95%,^[6] so a strong argument can be made for OIT being superior to avoidance alone.^[7] An ideal alternative, of course, would reduce accidental exposure risk without the attendant risks and side effects of OIT.

This epicutaneous therapy (EPIT) has shown some efficacy in children aged 6-11 years. Results showed that 50% achieved the primary endpoint of either tolerating a 300-mg peanut challenge or a 10-fold diminution in sensitivity as assessed by challenge, as opposed to 25% of placebo-treated patients. The response rate increased from 50% to 68% after a 24-month extension of the trial, suggesting that EPIT may have a more gradual onset of action.^[8] As to tolerability, most patients had irritation at the patch test site, but the study drug did not cause any serious adverse reactions, which enabled over 95% adherence and a negligible dropout rate. A further advantage of EPIT is that it has not been reported to cause GI symptoms or eosinophilic esophagitis. Could EPIT even be a viable treatment for eosinophilic esophagitis?

Understandably, many worried parents of children with food allergies have sought out allergists in private practice who have been willing to accommodate them by performing office-based OIT. Fortunately, no OIT deaths have been reported to date, but that risk will always exist regardless of whether this treatment receives US Food and Drug Administration (FDA) approval.

One way to attenuate the risk of OIT is with the monoclonal anti-IgE antibody omalizumab, which enables more rapid up-dosing with reduced risk.^[3] Omalizumab is also a viable stand-alone therapy for IgE-mediated food allergy (80-fold increase in peanut threshold), although it is not FDA-approved for this use.

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