For Egg Allergy Oral Immunotherapy, Low-Dose Liquid May Be a Key to Success

For egg-allergic children, an oral immunotherapy (OIT) protocol using low-dose liquid egg to start appeared to be the most successful in inducing tolerance in the outpatient setting, according to one academic center’s experience.

Compared with a protocol using either baked egg or high-dose liquid egg, OIT success was higher in those given low-dose liquid egg as indicated by 94% of patients becoming able to freely eat eggs as components of baked goods like cookies plus tolerate at least 3 g of egg on its own (17 of 18 vs 54 of 78 with the other two protocols combined, P<0.001).

Measuring success with a formal food challenge with 12 g of egg protein, the low-dose native egg protocol again came out on top, with 78% passing the test (14/18) compared with 61% (31/51) on the high-dose egg protocol and 44% (12/27) with baked egg for OIT, Antonella Cianferoni, MD, PhD, of Children’s Hospital of Philadelphia, and colleagues reported in the Annals of Allergy, Asthma & Immunology.

Oral immunotherapy for egg allergy has been proven effective at desensitizing allergic children in multiple studies since the 2012 Consortium of Food Allergy Research trial showed sustained benefits after a protocol with egg white powder OIT. However, standardization of protocols and broad uptake in allergy clinics didn’t coalesce the same way as in the peanut-allergy OIT arena, which had clinical trials for FDA approval of commercial products.

Some 60% of children outgrow egg allergy by adolescence, and American allergy and immunology societies don’t endorse egg OIT for them.

“It’s not for everybody, but a lot of patients that do our protocol express gratitude for being able to do it,” Cianferoni told MedPage Today.

While their protocols don’t break new ground, she said the group hopes that publishing their findings helps other practices adopt egg OIT more widely to improve patient access, as waitlists for it are common.

The retrospective study examined outpatients who underwent egg OIT between 2018 and 2023 at Children’s Hospital of Philadelphia. More than ten board-certified allergists and allergy advanced nurse practitioners at the center screened patients and found 111 appropriate candidates who underwent initial dose escalation under one of the three egg OIT protocols that evolved over the study period.

Initially, all patients got a baked egg protocol: 1 g of baked cake containing a set amount of egg daily for 3 months, followed by 1 g of baked egg in pancake daily for 3-6 months, and then transition to a native egg OIT protocol using liquid pasteurized egg whites.

The 27 patients undergoing baked egg OIT had trouble sticking with the protocol, though. They were more likely to stop compared to the two native egg protocols (44% vs 19%, P<0.01).

“The volume was starting to become an issue,” Cianferoni said. “A lot of the kids felt that eating all this baked egg every day was becoming difficult to do.”

The protocol moved to high-dose native egg OIT, with patients updosed from 3.3 mg to 4 g of liquid pasteurized egg white daily, which could be diluted into juice or another liquid or cooked. After reaching the maintenance dose of 3 g (equivalent to half an egg) without incident, patients could start eating half a cooked egg and expand their diet to include baked goods containing egg products, like waffles and pancakes.

Children prefer liquid to powdered egg because it can be masked more easily, Cianferoni noted.

However, with this protocol, reactions were an issue. Failure due to reaction during the initial dose escalation challenge was more common than with the other OIT protocols (20% vs 4%, P<0.05). Epinephrine was needed by 30% of kids on the high-dose protocol compared with 7% on the baked egg protocol.

The protocol then changed to a low dose of native egg, with individuals up-dosed from 1.6 mg to 3 g using liquid pasteurized egg white. After reaching the 3 g threshold, patients could eat as much baked egg products as they wanted. The rate of epinephrine use was 10%, and all of these were during the initial dose escalation phase without administration either at home or during office visits to increase doses.

“In order to have the highest possible success rate, we decided … for everybody to go slow and to find the dose that the minimum amount of patients possible would react to, and they would stay on the dose more consistently with the highest possibility of finishing the protocol,” Cianferoni said.

Of the 96 patients who passed initial dose escalation to start OIT, all but three had a history of ingestion and adverse reaction to baked or native egg. The other three patients had egg serum immunoglobulin E level over 100 kUA/L and had experienced contact reactions. The cohort’s mean age was 8.4 years, and 43% of the treated patients were female.

One limitation of the study was the sequential progression of protocols, such that that “knowledge gained from performing the first two protocols could have impacted the outcomes of the third (low-dose) protocol,” the researchers noted. Also, all the patients started OIT prior to FDA approval of omalizumab (Xolair) for food allergy in 2024.