January 09, 2026
6 min read
Key takeaways:
- Peanut protein tolerance at 1 year was similar between 30 mg and 300 mg peanut oral immunotherapy maintenance doses.
- The number of systemic allergic reactions was lower in the 30 mg maintenance dose group.
More peanut-allergic children receiving a 30 mg maintenance dose for peanut oral immunotherapy vs. avoiding peanut tolerated at least 443 mg and 1,043 mg of peanut protein at 1 year, according to study results.
The study, published in The Journal of Allergy and Clinical Immunology: In Practice, noted that this dose is approximately one-eighth of a peanut.
Data were derived from Upton JEM, et al. J Allergy Clin Immunol Pract. 2025;doi:10.1016/j.jaip.2025.10.007.
Julia E. M. Upton
“Peanut immunotherapy reaching only a very low dose of 30 mg peanut protein can meaningfully raise reaction thresholds, meaning raising how much peanut can be safely eaten and potentially reducing risk from accidental exposures,” Julia E. M. Upton, MD, MPH, head of the division of immunology and allergy at The Hospital for Sick Children (SickKids), project investigator in the SickKids Research Institute and co-director of the SickKids food allergy and anaphylaxis program, told Healio.
“For clinicians who do not yet recommend or offer OIT, this study showed that even a very low dose was clearly superior to avoidance to raise the threshold of reaction and induce positive immune changes,” Upton said. “Importantly, the children assigned to the 30 mg dose had fewer systemic adverse events than those assigned to 300 mg.”
In a prospective, blinded, randomized controlled trial, Upton and colleagues assessed 51 children (median age, 10 years; 51% boys) with peanut allergy to uncover the impact of a very low peanut OIT (P-OIT) maintenance dose (30 mg) on tolerance, safety and laboratory parameters at 1 year vs. open label peanut avoidance and a 300 mg P-OIT maintenance dose.
“[My colleagues and I] had noticed a few things that made us wonder if very low doses of that food may make OIT safer and easier,” Upton told Healio. “If the OIT dose causes allergic symptoms, dropping the dose for a few weeks to months then often results in a higher dose being tolerated.
“We also noticed that many children dislike eating large amounts of the food they are allergic to, and we wondered if a lower dose may be preferable,” she said.
Additionally, Upton said this study was prompted by results from treatment given under the tongue and through the skin.
“There have been positive results for peanut treatment with extremely low doses of peanut protein under the tongue (typically 1 mg to 4 mg) and through the skin (less than 1 mg),” she told Healio.
Included children were reactive to 444 mg peanut protein or less in double-blind placebo-controlled food challenges (DBPCFCs), and 44 mg of peanut protein was the initial cumulative-tolerated dose in the total cohort, according to the study.
Results
Each group included 17 children. DBPCFC completion was achieved by 15 children in the group assigned to the 30 mg peanut protein maintenance dose, 12 children in the group assigned to the 300 mg peanut protein maintenance dose and 12 children in the avoidance group.
Notably, the two children in the 30 mg group who did not complete DBPCFC were deemed ineligible. No children in this group withdrew from the study, whereas three of the children in the 300 mg group did.
“I was surprised to see that no children withdrew from the 30 mg dose group [while] three withdrew from the 300 mg dose group,” Upton said.
“It was unexpected that there were five children who withdrew from the avoidance group, even though they had the option of treatment at 1 year,” she added. “This withdrawal from avoidance may speak to families wanting treatment.”
Tolerance, safety
Compared with the avoidance group, researchers found that significantly more children receiving the 30 mg maintenance dose for P-OIT tolerated 443 mg or higher of peanut protein at 1 year (13 [76.5%] vs. 0; P < .001). Similarly, the number of children who tolerated 1,043 mg or higher of peanut protein at 1 year was significantly larger in the 30 mg maintenance dose group vs. the avoidance group (7 [41.2%] vs. 0; P = .007).
Between the 300 mg P-OIT maintenance dose group and the avoidance group, significantly more children receiving OIT tolerated 443 mg or higher of peanut protein at 1 year (10 [58.8%] vs. 0; P < .001), as well as 1,043 mg or higher of peanut protein (8 [47.1%] vs. 0; P = .003) at 1 year.
“The proportion of children who tolerated 443 mg or greater [peanut protein] or 1,043 mg or greater [peanut protein] in each P-OIT group was similar,” Upton and colleagues wrote.
Changes in specific IgE and specific IgG4 from before to after P-OIT observed in the 30 mg group did not differ from those observed in the 300 mg group, according to the study. When compared with the avoidance group, both groups had significantly improved specific IgE and specific IgG4.
Between study entry and the 12-month mark, researchers also reported that children in the 30 mg group had lower median skin prick test (8 mm to 5 mm; P = .01), and the same was true for children in the 300 mg group (7.5 mm to 4.25 mm; P = .05).
“The finding that OIT with only 30 mg peanut protein for about a year can have meaningful clinical and laboratory changes challenges the long-standing assumption that much higher doses (hundreds or thousands of milligrams) are necessary for success,” Upton told Healio.
“The median tolerated amount at the start of the study was 30 mg, so for many of the children the 30 mg was their initial tolerated dose or lower (44 mg was the average/median tolerated dose at study entry) and yet this was enough to drive immune changes and see an increase in how much peanut a child could safely eat,” she continued.
In terms of safety, there was a total of 269 systemic allergic reactions in the 30 mg group, which was less than the 323 reactions that occurred in the 300 mg group. Similarly, the number of moderate or severe non-anaphylactic systemic reactions (single organ system only) was lower in the 30 mg vs. 300 mg maintenance dose group (36 vs. 88).
Impact, future studies
Reflecting on the study as a whole, Upton told Healio there are several potential benefits of lower P-OIT doses.
“Lower doses may reduce systemic reactions, require fewer up-dosing visits and potentially improve adherence, making OIT more practical for families,” she said. “For clinicians who manage patients on OIT, if their patient is struggling with the OIT dose due to reactions or dislike, they may consider dropping the dose to a well-tolerated dose rather than returning to avoidance.
“Overall, a little OIT can go a long way to teach the immune system to be less reactive to a food a patient is allergic to,” Upton continued.
Looking ahead, Upton told Healio the lowest possible dose below which OIT does not work has not been found yet.
“Therefore, I think attention will continue on low, slow approaches,” Upton said. “It would be interesting to study many aspects of very low dose OIT.
“One example is using very low doses for years and then jumping to a new dose to reduce medical visits and cost,” she continued. “This approach has been explored in under the tongue immunotherapy and after years of through the skin immunotherapy.”
Importantly, Upton noted that the presented study did not look into whether the typical restrictions of OIT can be lifted with very low doses.
“These restrictions include lowering the dose when ill and avoiding exercise within a few hours of the dose,” she told Healio. “These activities can reduce the amount of peanut that triggers a reaction so a patient requires dose management. With the under the tongue and through the skin approaches there are typically no dosing changes.”
Studies on the impact of treatment longer than 12 months and real-world use are in the works, according to Upton.
“We did evaluate these children again at 21 months of treatment, so we will soon report the longer-term experience with these doses,” she said. “We have [also] implemented this low-dose approach in our immunotherapy clinics and are currently reviewing our experience to report on the real-world use of this approach.
“I think we will see fewer and fewer immunotherapy studies with an avoidance arm as immunotherapy becomes more widely offered,” Upton added.
For more information:
Julia E. M. Upton, MD, MPH, can be reached at julia.upton@sickkids.ca.
Sources/Disclosures
Source:
Upton JEM, et al. J Allergy Clin Immunol Pract. 2025;doi:10.1016/j.jaip.2025.10.007.
Reference:
Disclosures:
This study was funded by the Canadian Institutes of Health Research, the Montreal Children’s Hospital Foundation, the SickKids Food Allergy and Anaphylaxis Program, and the U.S. Peanut Advisory Board. Upton reports receiving grants or contracts from ALK-Abelló, the Canadian Institutes of Health Research, DBV Technologies, Innovation Fund Denmark, Regeneron, Sanofi and the SickKids Food Allergy and Anaphylaxis Program; honoraria from AstraZeneca, Pear Healthcare, Pfizer and Viatris; participation on the advisory board for ALK-Abelló, Bausch Health, Pfizer and Pharming; a leadership role in Allergy (editorial board), Allergy, Asthma & Clinical Immunology (associate editor), Annals of Allergy, Asthma & Immunology (editorial board), the Canadian Society of Allergy and Clinical Immunology and Food Allergy Canada; and receipt of drug (omalizumab) from Novartis for research study, all outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.
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