More than one third of infants referred for peanut oral immunotherapy (OIT) were found not to be allergic when formally challenged, according to findings from Australia’s national ADAPT Peanut OIT Program.

The negative challenges occurred despite a history of peanut reactions and evidence of sensitization on skin-prick tests or Immunoglobulin E (IgE) tests, said Tim Brettig, MBBS, PhD, a pediatric allergist and immunologist at the National Allergy Centre of Excellence and Murdoch Children’s Research Institute in Melbourne, Australia.

“The findings suggest that many infants may be unnecessarily labelled as peanut allergic and could avoid both long-term dietary restriction and immunotherapy treatment. That creates an important opportunity for early and accurate delabelling.”

Brettig presented the results at the European Academy of Allergy and Clinical Immunology (EAACI) 2026 Annual Congress.

Unlike most OIT studies, ADAPT is not a clinical trial but a national model of care. Launched in 2024 in collaboration with 10 public pediatric hospitals across five Australian states, Brettig described the effort as the world’s first nationally standardized peanut OIT program for infants. Running alongside it is the ADAPT OIT Evaluation Study, an embedded retrospective evaluation.

“One of the key things that makes the ADAPT OIT program different is that it is the world’s first nationally standardized clinical program for food allergy treatment, not a trial itself,” Brettig told Medscape Medical News. “The evaluation study is designed to provide data in near real time so that we can continuously improve the program.”

By providing continuous feedback to clinicians from all participating centers, the evaluation is designed to improve safety, quality, and service delivery. The program also takes a pragmatic approach, using commercially available peanut flour and simple teaspoon measurements rather than specialized products, with the aim of supporting a sustainable model within the public healthcare system, Brettig said.

Confirming Peanut Allergy

OIT is increasingly used to increase tolerance to peanut and reduce the risk for allergic reactions following accidental exposure, but oral food challenges before treatment are not routinely performed in many centers. Instead, diagnosis often relies on clinical history and allergy biomarkers.

But confirming allergy before treatment is important not only to avoid unnecessary therapy but also because challenge testing can identify the threshold dose that provokes symptoms, allowing clinicians to individualize starting doses, Brettig said.

Eligible infants had experienced an IgE-mediated peanut reaction before 12 months of age and had evidence of sensitization on skin-prick testing or specific IgE testing. Children with mild-to-moderate previous reactions underwent a threshold oral food challenge (TOFC) consisting of seven escalating doses of peanut flour ranging from 15 mg to 1300 mg (roughly one teaspoon) of peanut protein.

If a reaction occurred, the eliciting dose was used to determine the starting dose of OIT. For non-anaphylactic reactions, the starting dose was set one step below the threshold dose, and for anaphylactic reactions, two steps below.

One Third Passed Challenge Testing

Between April 2024 and October 2025, 1244 infants were assessed across the 10 participating centers. Of these, 778 (62.5%) underwent TOFCs at a median age of 13 months. Overall, 65.2% had a positive allergic challenge, whereas 34.8% passed the challenge and were subsequently delabelled as peanut allergic.

Among infants with positive challenges, the median eliciting dose was 0.125 teaspoon (120 mg) of peanut protein, equivalent to approximately 0.25 teaspoon of peanut flour. Most reactions were mild and consisted primarily of urticaria.

Anaphylaxis Occurred but Managed Safely

Among 778 infants who underwent TOFCs, anaphylaxis occurred in 61 (7.8%), according to the researchers.

Two infants required infusions of adrenaline and admission to the ICU for persistent hypotension, whereas one required two doses of intramuscular adrenaline. All recovered fully without sequelae.

Importantly, Brettig noted, anaphylaxis occurred across the full range of challenge doses rather than being concentrated at higher doses, underscoring the importance of performing food challenges in appropriately resourced centers.

Investigators also examined whether commonly used allergy biomarkers could predict reaction severity or threshold. Infants with positive challenges had larger median wheal sizes (7 mm vs 5 mm) after skin-prick tests and higher median Ara h 2-specific IgE levels (2.1 kUA/L vs 0.3 kUA/L) than those with negative challenges.

However, neither marker reliably predicted reaction threshold, severity, or likelihood of anaphylaxis. Investigators did identify high-certainty diagnostic thresholds. All infants with a skin-prick test wheal size of at least 12 mm or an Ara h 2-specific IgE level of at least 5.0 kUA/L were confirmed to be allergic, corresponding to 100% specificity at those cutoffs. No infant with an Ara h 2 level above 5 kUA/L had a negative challenge, the researchers reported.

Personalized Dosing Appears Successful

At the time of analysis, 376 infants had commenced OIT. Of these, 97.1% successfully tolerated their personalized starting dose, determined by the threshold food challenge, Betting and his colleagues reported. Challenge-guided dosing not only improved safety but also reduced the number of up-dosing visits required to reach maintenance treatment compared with more traditional protocols, an important consideration for resource-constrained public allergy services, he added.

Ruperto González-Pérez, MD, PhD, a consultant allergist at the Hospital Universitario de Canarias, in Santa Cruz de Tenerife, Spain, called the study “really impressive.”

“I think it is really useful for routine practice,” said Canarias, who co-moderated the session.

Brettig said the current findings represent only “the tip of the iceberg” for the ADAPT program.

“We now have more than 870 children enrolled in oral immunotherapy nationally,” he said. “The first cohort will begin completing the 2-year program from July, when they will undergo follow-up food challenge assessments after an 8-week treatment pause to assess sustained unresponsiveness.”

The growing national database will allow investigators to evaluate long-term outcomes and use the findings to continuously refine the program. “One of our biggest challenges is understanding how we can deliver this more effectively and sustainably. That may involve exploring improved models of care, including expanding to other food allergens, telehealth, or expanding delivery to additional sites. We’re really trying to use the evidence generated through the program to guide our decisions as we move forward.”

Brettig and González-Pérez reported no relevant financial conflicts of interest.