New world-first Australian research has experts calling for supervised oral challenges to be routinely considered, to both confirm an allergy and guide immunotherapy dosing.
A world-first national peanut oral immunotherapy program has found that 34.8% of infants suspected of having a peanut allergy tolerated the food during supervised oral challenges.
The findings suggest that clinical history and allergy sensitisation tests alone may not be sufficient to establish a diagnosis in infants who have previously experienced an allergic reaction.
The researchers said the results also demonstrated that challenges could be used to successfully establish an appropriate starting dose for oral immunotherapy (OIT) in the vast majority of infants with a confirmed peanut allergy.
The study, published in The Journal of Allergy and Clinical Immunology: In Practice, evaluated the diagnostic accuracy and safety of threshold oral food challenges (TOFCs) before commencing treatment through Australia’s Allergy Development to an Accelerated Pathway to Tolerance (ADAPT) program.
Among 778 infants who underwent a TOFC, 271 had no allergic reaction despite a history of a previous reaction to peanut and evidence of sensitisation on allergy testing.
These infants were considered peanut tolerant and could have their allergy diagnosis removed, allowing them to regularly consume peanut in an age-appropriate form rather than continue unnecessary allergen avoidance.
The research was a collaboration between the Murdoch Children’s Research Institute (MCRI), the National Allergy Centre of Excellence (NACE) and 10 paediatric public hospitals across Victoria, New South Wales, Queensland, South Australia, and Western Australia.
“Our results show that clinical history and allergy testing alone were not enough to accurately diagnose peanut allergy in many cases. A supervised oral food challenge should be routinely considered to confirm the diagnosis before an infant starts oral immunotherapy,” said Professor Kirsten Perrett, MCRI Population Allergy Group leader, NACE Director, and ADAPT Program lead.
“With peanut allergy one of the most common childhood food allergies, it’s particularly important that we have an accurate diagnosis when a baby first shows signs of a possible peanut allergy. We want to reduce the burden of food allergy for children and their families, and the ADAPT Program is a step in this direction.”
Australia has some of the highest reported rates of childhood food allergy in the world, with peanut allergy affecting approximately one in 30 children.
MCRI Population Allergy Group Senior Research Clinician and ADAPT Medical Lead Dr Tim Brettig said the findings highlighted the importance of confirming a peanut allergy before committing children to long-term treatment.
“Being able to identify those children early allows them to avoid an unnecessary allergy label and the burden of avoiding peanut,” he said.
Launched in 2024, ADAPT is the first nationally standardised model of care for peanut allergy treatment and the first peanut allergy treatment program offered in Australian public hospitals for infants outside a clinical trial setting.
It was designed to provide a standardised approach to peanut OIT for infants with a history of an IgE-mediated allergic reaction to peanut before 12 months of age and evidence of sensitisation.
Eligibility required a previous Consortium for Food Allergy Research (CoFAR) grade 1 or 2 reaction to peanut, alongside sensitisation (a positive skin prick test [SPT] of at least 3mm or peanut-specific IgE (sIgE) or Ara h 2 sIgE of at least 0.35kUA/L).
Under the program, eligible infants underwent a TOFC before commencing OIT. The challenge served two purposes: confirming whether the infant had a peanut allergy and determining the amount of peanut that triggers a reaction, which was subsequently used to guide the starting dose of immunotherapy.
The researchers noted that oral food challenges (OFCs) were not routinely performed before OIT in many settings, partly because of concerns about safety, time and resource requirements, or the belief that a convincing clinical history combined with a positive sensitisation test was sufficient to establish the diagnosis.
However, they argued that this approach risked exposing infants and their families to unnecessary allergen avoidance and potentially several years of treatment.
The study assessed 1275 infants under 18 months of age between April 2024 and October 2025. Of these, 778 (62.5%) proceeded to a TOFC, while 59 infants with a convincing history of a CoFAR grade 3 reaction underwent a separate escalation OFC.
A further 438 infants eligible for either challenge did not proceed. Reasons included parents or carers declining OIT in favour of allergen avoidance, geographical barriers, concerns about treatment safety and parental anxiety about potential allergic reactions.
Baseline characteristics were similar between those who proceeded to an OFC and those who did not.
For infants undergoing a TOFC, the median age was 13 months. The median time from the initial reaction to the first allergy clinic assessment was three months, while the median interval between the initial reaction and completion of the TOFC was six months.
Most infants lived in metropolitan areas (88.9%), with relatively few Indigenous Australian patients represented in the cohort (1.5%). At the initial assessment, 65.7% of infants had a diagnosis of atopic dermatitis or eczema, and 52.7% had no other known food allergies.
The TOFC involved seven escalating doses of peanut protein, ranging from 15mg to 1300mg, administered at 15-minute intervals under medical supervision. Doses could be delayed at the treating clinician’s discretion if there were evolving signs of an allergic reaction.
The proportion of negative challenges was higher than the researchers had anticipated, suggesting that a substantial number of infants previously considered allergic might otherwise have continued to avoid peanut unnecessarily.
The findings also raised the possibility of transient peanut allergy, in which an initial immune response following peanut ingestion resolved over a relatively short period or did not translate into an ongoing reaction with subsequent exposure.
The researchers noted that comparable data on OFC outcomes are limited because challenges have traditionally been performed more selectively, often in patients considered more likely to have a negative result.
Among infants with a history of a CoFAR grade 1 or 2 reaction and a positive sensitisation test, the conventional approach before ADAPT would generally have been to diagnose peanut allergy and recommend allergen avoidance.
The researchers suggested that the substantially higher proportion of infants identified as peanut tolerant through ADAPT reflected the value of incorporating a systematic challenge into the diagnostic pathway rather than relying on more selective testing.
Median peanut SPT results were 7mm among infants with a positive challenge, compared with 5mm among those with a negative challenge. The presence of eczema (P<0.001) and additional food allergies (P=0.010), particularly cow’s milk allergy (P=0.015), were also associated with a positive challenge.
However, sex, treating site, language spoken at home, age at initial reaction, age at challenge, and CoFAR grade of the initial reaction were not significantly associated with challenge outcomes.
The researchers also assessed the diagnostic performance of the biomarkers.
An Ara h 2 sIgE cutoff of 2.0kUA/L provided a 95% positive predictive value (PPV), with a specificity of 96.5% (95% CI 90.1–99.3). All infants with results of at least 5.0kUA/L reacted during the TOFC, corresponding to 100% specificity in this cohort.
For peanut SPT, an 11mm cutoff provided a 95% PPV, with a specificity of 98.9% (95% CI 96.7–99.8). All infants with results of at least 12mm reacted during the challenge.
The area under the receiver operating characteristic curve was 0.815 for Ara h 2 sIgE and 0.714 for peanut SPT, suggesting that Ara h 2 performed better as a biomarker. However, neither test could reliably predict the eliciting dose or severity of an allergic reaction.
Additionally, SPT and Ara h 2 sIgE results were similar among infants who experienced anaphylaxis and those who had non-anaphylactic reactions; the median SPT was 7mm and median Ara h 2 sIgE was 3.1kUA/L for the former, and 7mm and 2.0kUA/L respectively for the latter.
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The researchers said these findings suggested that sensitisation biomarkers could not be used to predict either the dose at which an infant would react or the severity of the reaction.
Of the 507 positive TOFCs, 12.0% involved anaphylaxis, representing 7.8% of all 778 challenges. The most common symptoms among infants with positive challenges were urticaria (85.8%), pruritus (22.5%), and angioedema (17.6%).
Among the 29 infants with a history consistent with a CoFAR grade 3 reaction who underwent a TOFC rather than an escalation challenge, 48.3% did not react and were considered peanut tolerant.
The researchers said all challenge-related reactions were safely managed by the teams conducting the assessments. However, they emphasised that the approach carried a higher likelihood of anaphylaxis than traditional OFCs, primarily because the ADAPT protocol included infants with a higher likelihood of a positive result.
They said this meant TOFCs should be performed in centres with appropriate medical support and facilities to manage severe allergic reactions.
For infants who reacted during their TOFC, the challenge results were subsequently used to determine the starting dose for peanut OIT.
For the treatment, which involves daily peanut doses that are gradually increased to build tolerance, the individual’s starting dose was determined by the eliciting dose during the TOFC, with treatment commencing one dose below the eliciting dose for non-anaphylactic reactions and two doses below for anaphylactic reactions.
Up-dosing visits were scheduled every four weeks under supervision until the maintenance dose of 650mg of peanut protein (1/2 teaspoon of peanut flour) was reached. Infants were observed for two hours following each visit, and their families received training and written instructions on dose measurement and pre- and post-dosing requirements in line with established OIT guidelines.
Of the 507 infants with positive TOFCs, 394 had commenced the ADAPT program through the TOFC pathway at the time of the analysis. A further 113 (22.3%) had not proceeded to treatment despite a positive challenge or were waitlisted to commence.
Of those who commenced treatment, 97.5% successfully initiated OIT at the first up-dosing visit at a dose below their TOFC-determined reaction threshold.
Among the 10 infants who did not successfully commence at the planned dose, nine had their dose reduced and continued in the program; one infant could not tolerate the 3mg dose and discontinued treatment because a lower practical dose could not be reliably achieved.
The researchers said the results demonstrated that TOFCs could be used not only to confirm the diagnosis but also to establish an appropriate starting dose for OIT in most infants.
They said the findings highlighted a potential trade-off between the safety and diagnostic accuracy of different approaches to infant peanut allergy management.
Although OFCs were time- and resource-intensive and can cause anaphylaxis, avoiding them may result in children being incorrectly diagnosed and exposed to unnecessary treatment or long-term allergen avoidance.
They noted that TOFCs could also allow OIT to commence at a higher starting dose, potentially reducing the number of up-dosing steps required to reach maintenance treatment.
However, the researchers acknowledged the practical issues of TOFCs.
“Although the ADAPT program identifies the importance of a threshold OFC to confirm peanut allergy before commencing OIT, OFCs remain time- and resource-consuming and are the bottleneck in patient flow through the diagnostic process, and therefore into the OIT program,” they noted.
“Using the TOFC approach results in higher overall rates of anaphylaxis compared with traditional OFCs (ie, those used when the diagnosis is unclear from the clinical history, or allergy is suspected to be outgrown) and also higher rates compared with simply starting OIT based on the clinical history and biomarkers, but the trade-off for avoiding these extra anaphylaxis events is a reduction in accurate diagnosis.”
They said confirming allergy before commencing OIT could reduce the number of families who needed to commit logistically and emotionally to an unnecessary treatment program, as well as reducing the clinical resources required to deliver immunotherapy because fewer patients require it.
Additionally, they argued that confirming the diagnosis should not be limited to those being considered for OIT, given that a negative challenge could allow families to reintroduce peanut and avoid the burden of unnecessary food restrictions.
“We strongly recommend considering this approach for diagnosing peanut allergy in infants regardless of whether OIT or an allergen avoidance strategy is pursued,” they wrote.
“Accurately confirming allergy via OFC in infants can reduce the burden of allergy for patients, families, and society through misdiagnosis, and before the commencement of OIT, it can help avoid unnecessary treatment.”
The ADAPT program continues, and will also follow the infants who have a negative TOFC, with reassessment at two years to determine whether any have redeveloped peanut allergy after their initial negative challenge.
The Journal of Allergy and Clinical Immunology: In Practice, 5 November 2026
