High-dose, rapid-escalation oral immunotherapy (OIT) with an adjunct probiotic was effective for treating hen’s egg and milk allergies in children, the small, open-label PREMO trial from Australia found.

Reporting findings in Pediatric Allergy and Immunology, Mimi L.K. Tang, MD, allergist/immunologist at Murdoch Children’s Research Institute in Melbourne, and colleagues said the treatment strategy may increase the likelihood of achieving sustained unresponsiveness (SU) and shorten the required treatment period.

“The findings provide observational evidence that this approach was highly effective at binding remission of allergy,” Tang told Medscape Medical News. “We now need to confirm efficacy and safety in a blinded, placebo-controlled, randomized trial.” 

Alongside peanuts, hen’s eggs and cow’s milk are among the three most common causes of pediatric immunoglobulin E-mediated food allergies. 

“In Australia, egg allergy is the single most common food allergy during infancy, but because the majority — about 80% — resolve during school years, peanut and tree nuts assume greatest prevalence by late primary and early secondary school,” said Tang.

High-dose, rapid-escalation OIT previously proved successful for treating peanut allergy in the PPOIT-003 study, achieving high SU rates of 46%-74%.

The current open-label proof-of-concept trial enrolled 40 girls and boys ages 5 to 17 (mean age just over 9 years) with egg (n = 20) or milk (n = 20) allergy as confirmed by double-blind placebo-controlled food challenge (DBPCFC). The children received the gut-friendly probiotic Lactobacillus rhamnosus GG and appropriate OIT for 18 months, with SU assessed by DBPCFC posttreatment and after 8 weeks of dietary allergen exclusion. “We selected L rhamnosus GG based on its many tolerogenic effects,” Tang said.

The primary outcome was the proportion completing the dose-escalation phase; secondary outcomes were the proportion achieving SU, adverse events, and change in health-related quality of life (HRQOL).

Nine (45%) egg and seven (35%) milk OIT participants completed dose escalation, and 17 (85%) in both groups were able to reach the maintenance phase with appropriate dose modifications. Eleven (55%) egg and 10 (50%) milk participants attained SU, and clinically significant improvements in HRQOL were observed in both groups.

Treatment-emergent adverse events, however, were frequent, with moderate or severe episodes documented in nine (45%) egg and 13 (65%) milk participants. Adverse events included gastrointestinal, respiratory, skin, and cardiovascular manifestations, and more than half of the participants required dose adjustments. Three quarters of treatment completers achieved SU and improved quality of life.

“The very high levels of SU attained during PREMO suggest that the combination of rapid updosing with a minimum of 12 months of maintenance dosing may offer an efficient and effective treatment option for many patients,” the authors wrote. “Clinicians practicing OIT should consider the trade-off between the speed of up-dosing and the required duration of maintenance dosing.”

As to an adjunct probiotic, while it may have enhanced efficacy, it was not supported by results from PPOIT­003, in which a probiotic reduced gastrointestinal symptoms but did not lead to higher SU rates.

Offering a US perspective on the study, Jeffrey Factor, MD, executive director of the New England Food Allergy Treatment Center in West Hartford, Connecticut, commended the authors for showing that their protocol resulted in many patients reaching maintenance and attaining SU.

“But this was an uncontrolled open-label study without a placebo arm, and that limits the significance of their findings and observations with probiotic therapy,” he told Medscape Medical News. “Additionally, there’s the high occurrence rate of adverse reactions, many of which were classified as moderate-to-severe, in the study populations — both egg, 45%, and milk, 65%. These levels are high and would warrant a less aggressive protocol.”

As to adjunct probiotic therapy, the emergence of biologics such as omalizumab, now approved for preventing anaphylaxis due to multiple food allergies, could make other adjuncts such as probiotics less desirable, Factor said.

Tang’s group is investigating potential patient factors that modify treatment efficacy. “We will continue to examine available data to gain a deeper understanding of key effect modifiers of OIT,” she said.

This study was jointly funded by Prota Therapeutics and Murdoch Children’s Research Institute. Tang disclosed receiving consultant fees from CSL Seqirus and Pfizer, as well as interest/options in Prota Therapeutics. She reported being a member of the medical advisory board of Anaphylaxis & Anaphylaxis Australia, the board of directors of the Asia Pacific Association of Allergy, Asthma, and Clinical Immunology, AllergyPal, and Prota Therapeutics; and expert committees of the American Academy of Allergy, Asthma, & Immunology, the Asia Pacific Association of Allergy, Asthma, and Clinical Immunology, and the Australasian Society of Clinical Immunology and Allergy.

Co-author Loke reported receiving consultant fees from SPRIM Consulting and an institutional grant from Siolta Therapeutics, outside of the submitted work. Factor reported having no relevant conflicts of interest.