Low-dose oral immunotherapy (OIT) increased tolerance to peanut in allergic children about as well as higher-dose OIT, new research finds. Low-dose OIT also desensitized with fewer treatment-related reactions.
The results suggest that OIT using even a very small amount peanut protein – about one-eighth of a peanut kernel was the maximum daily dose – can protect against reactions from accidental exposure, says co-lead study author Dr. Julia Upton. She’s division head of immunology and allergy at Toronto’s Hospital for Sick Children, which collaborated with Montreal Children’s Hospital on the research.
In standard OIT treatment, patients gradually increase the amount of a food allergen they consume until they reach a daily maintenance dose. With peanut that’s often 300 mg of peanut protein (or higher) for achieving desensitization. To maintain tolerance, patients must continue eating their maintenance dose on a regular basis.
However, Upton and her colleagues decided to test whether peanut-allergic children could reach and maintain desensitization with far less of the food.
The study included 51 peanut-allergic children ages 2 to 18. The kids were randomly assigned to one of three groups: higher-dose OIT, low-dose OIT or peanut avoidance. Neither doctors nor patients knew which OIT dose participants were receiving.
At the start, children could tolerate an average of just 44 milligrams (mg) of peanut protein, or about one-fifth of a peanut kernel, before reacting.
Children in the low-dose group started therapy on a 0.5 mg dose of peanut protein daily, which escalated to a 30 mg maintenance dose. The higher-dose group followed the same starting dose, but escalated to 300 mg, roughly one peanut.
After one year of treatment, children underwent an oral food challenge to determine how much peanut they could tolerate.
Findings: Low-Dose Approach Worked
Children in both peanut-exposure groups showed substantial gains in tolerance. In the low-dose group, 13 of 17 children tolerated at least 443 mg of peanut protein. Seven of them tolerated more than 1,000 mg. That’s equivalent to about four peanuts.
In the higher-dose group, 10 of 17 children tolerated at least 443 mg. Eight tolerated more than 1,000 mg. None of the children in the avoidance group reached these thresholds.
“The purpose of this study was to see whether or not a 30-mg dose works, whether it induces immune changes, and whether it increases the amount of food a child can eat safely,” Upton says. “And we’ve shown that 30 mg works.”
Eight children dropped out over the course of the study. This included five in the peanut avoidance group and three in the 300-mg OIT group (two for anxiety and one for a suspected eosinophilic esophagitis reaction).
No children in the 30-mg group dropped out. Several children were excluded from the study early on because they reacted to the first doses of peanut.
The incidence of anaphylaxis, defined as symptoms involving two or more organ systems, was low in both OIT groups. However, children in the higher-dose group experienced a five-fold higher rate of allergic reactions involving a single organ system, such as hives, nausea or stomach pain.
How Low Can You Go?
The study’s findings also raise an intriguing question: just how little peanut protein is enough to provide protection?
Based on the persuasive results, Upton suspects doses even lower than 30 mg are likely to reduce the risk of reactions from accidental exposures.
“How low can you go?’” Upton says.
OIT has been shown in numerous studies to be highly effective in increasing tolerance to peanut, the process known as desensitization. But the therapy has drawbacks.
Reactions during dose escalation and even during maintenance are common. Symptoms are often mild, such as an itchy mouth or stomach pain. But they can include more severe reactions, such as vomiting or anaphylaxis.
Maintenance dose levels in OIT do vary. The FDA-approved peanut OIT treatment, Palforzia, uses a 300 mg maintenance dose. Many allergists also use that level when using peanut foods as therapy. Others aim much higher, sometimes thousands of milligrams.
When launching the low-dose OIT study, Upton and her colleagues wanted to test if a low and slow strategy could still shift the immune response while reducing side effects.
“What dosing do you need to be able to shift the immune system immunologically as well as clinically to increase the threshold of reactions?” Upton says.
Hints of Higher-Dose Benefits
The study findings also suggest that higher-dose OIT may offer some advantages. Blood tests showed a similar increase in IgG4 antibodies, which are associated with tolerance, in both the 30-mg and 300-mg groups.
But the 300-mg group was less reactive on a basophil activation test (BAT). BAT is a lab test that measures how strongly a type of white blood cell responds to allergen exposure. This suggests that the higher-dose OIT may have a greater effect on a key immune driver of allergic reactions.
In an analysis limited just to children who completed OIT, those in the high-dose group were also more likely to tolerate 1,000 mg of peanut than those in the low-dose group – eight of 12 children, compared with seven of 15 in the low-dose group.
Although the difference wasn’t statistically significant, possibly due to a small sample size, “there is a suggestion that the 300 mg looks like it desensitizes a bit more,” Upton notes. The trade-off may be a higher rate of treatment-related reactions, she says.
Using Low-Dose OIT in Practice
Upton began offering low-dose OIT in her allergy clinic about three years ago. Low-dose OIT requires fewer office visits for updosing, which appeals to busy families. Lower doses may be easier for kids who dislike the taste of peanut, and more manageable for patients undergoing OIT for multiple nut allergies.
A recent small study by Upton and colleagues tested low-dose, multi-nut OIT in 18 children who had between two and five peanut and tree nut allergies. Patients updosed every two months until reaching a maintenance dose of 30 mg.
After 18 months of treatment, the median tolerated dose for each nut was 1,000 mg. Ten of 15 children could tolerate 2,000 mg of each nut, the maximum tested dose.
Reducing treatment-related reactions may help more patients to complete OIT and remain on maintenance long-term. Upton notes that even at the start of the peanut study, most kids could tolerate one-eighth of a peanut without symptoms. By staying at that dose, many children gained meaningful protection from accidental exposure without ever escalating further.
When patients experience frequent symptoms during OIT, “they think the process doesn’t work for them,” she says.
The allergist considers 30 mg an initial goal, not an endpoint. Patients can stay at that dose if they choose. Or, they can continue to escalate to 300 mg or beyond to further increase their reaction threshold.
Low-dose OIT “opens flexibility to the OIT protocols,” Upton says. “Rather than quitting and going back to avoidance, maybe an initial low-dose approach can move people from the fear of the food and an avoidance regimen onto an active treatment regimen.”
Related Reading:
In Toddlers, OIT Can Lead to Peanut Allergy Remission: Study
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