‘Very Low-Dose’ Peanut Oral Immunotherapy Helps Desensitize

Oral immunotherapy using even very small amounts of peanut helps with desensitization and protecting from reactions due to accidental ingestion, a new study finds.

Researchers at Toronto and Montreal hospitals divided 51 children with a peanut allergy into three groups of 17. One group was told to strictly avoid peanut. A second group received “very low-dose” OIT, starting with 0.5 milligrams (mg) of peanut and escalating to a maximum of only 30 mg. A third received OIT starting at 0.5 mg and escalating to 300 mg, or about one peanut.

At the start of this ongoing study, participants could eat an average of 44 mg of peanut, but no more than 144 mg of peanut, before starting to react.

A year after starting OIT, both OIT groups – those who topped out at 30 mg daily and those who topped out at 300 mg – could consume substantially more peanut than when they started.

Among those in the very low-dose OIT who have had a food challenge to date, 11 out of 13 allergic children ate a total of 443 mg of peanut without reacting. Six out of the 13 could even eat over 1,000 mg.

By comparison at the one-year challenge in the 300 mg group, 8 out of 10 children could eat 443 mg of peanut. Six out of the 10 tested to date could eat over 1,000 mg.

Lead study author Dr. Julia Upton is encouraged by the amount of peanut many of the very low-dose group could tolerate. “This suggests we may not need to be pushing and pushing people far above their limits. Rather, we can achieve a lot from staying within their initial limits,” says the allergist-immunologist at The Hospital for Sick Children in Toronto.

Very Low-Dose OIT: Likely Easier to Manage

Upton notes that more participants have yet to have their peanut challenges. She presented the research at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting in San Antonio, Texas.

In oral immunotherapy, allergic individuals eat small amounts of their allergen daily. The goal is to desensitize patients to the allergen, to increase the threshold before they react. After months of gradually increasing doses, patients settle onto a “maintenance” dose to maintain a level of tolerance.

Three hundred milligrams is a common maintenance dose for peanut oral immunotherapy, including for the FDA-approved OIT treatment, Palforzia.

“Very low dose OIT – only 30 mg – likely provides significant desensitization versus avoidance, and it provides a cumulative tolerated dose that is many times higher than maintenance,” says Upton.

OIT is highly effective – studies show that peanut (as well as egg and milk) desensitizes between 60 and 80 percent of people.

But not everybody can make it to 300 mg. Some experience reactions during OIT, including potentially anaphylaxis, and decide to discontinue treatment. Others experience side effects such as stomach pains or respiratory symptoms.

It’s possible that sticking to a lower dose may lead to fewer reactions and side effects, although Upton and her colleagues still need to complete that analysis in the research.

“I worry that some people who have trouble ‘up-dosing’ in OIT think they are not doing well, or that the treatment isn’t right for them, or they won’t get any benefit. Or their doctors may think this,” Upton says. “Showing that eating even a tiny bit can make a helpful change to peanut allergy is encouraging and may help them stick with it.”

Previous research by Japanese researchers have found that very low-dose OIT for dairy may provide some protection.

In the ongoing Canadian study, children in both the lower and higher-dose OIT groups continued to receive their daily peanut dose for 21 months, when they underwent another food challenge. Results for both dosing strategies continued to look good. Of the very low-dose OIT group tested so far, 7 of 9 consumed a total of 443 mg of peanut without reacting. Five out of the 9 could eat over 1,000 mg.

At 21 months in the 300 mg group, 5 out of 6 who’ve done the challenge had success at 443 mg. Five of the 6 also could eat over 1,000 mg. (Upton noted that they had more dropouts in the 300 mg group.)

How Low Dose Can We Go?

There are potentially other benefits to lower-dose OIT as well. Some people struggle with the taste of peanuts. Thirty milligrams “is a very small amount and is not arduous to eat for most,” Upton says.

She suggests very low-dose OIT might make it easier for people to do OIT for multiple foods. This is since they’d need to eat less peanut to maintain desensitization to that one key allergen.

As well, lower dose OIT could help to make OIT more accessible. It takes fewer visits to reach 30 mg, which could make OIT less time-consuming and less costly.

“An initial very low-dose OIT approach may allow for widespread access and widespread increases in the protection against peanut,” Upton says.

She’s also interested in whether an even lower dose of peanut could provide protection. “In this study, very low-dose OIT is giving meaningful increases in peanut threshold dose. Therefore, we still haven’t found how low can we go, or the lowest dose of OIT that gives meaningful protection. Even lower may have value, too.”

And, she notes, those who reach the 30 mg dose and want to continue onto the higher dose could do so.

5 Years of Palforzia: Decreasing Reactions

Also at the AAAAI meeting, researchers presented data on up to 5.5 years of daily oral peanut immunotherapy using Palforzia in children ages 4 to 17.

Dr. Andrew Bird, a professor of pediatrics and internal medicine at University of Texas Southwest Medical Center, and colleagues pooled data on 1,127 children from three controlled Phase 3 trials. These included PALISADE, RAMSES, and ARTEMIS, and three open-label extension trials.

They found 91 percent of children had one or more treatment-related allergic reactions, the most common being wheezing or other respiratory symptoms, and stomach pain. Of those, 58 percent of symptoms were considered mild and 26 percent were moderate.

Reactions mostly occurred during the approximately six-month up-dosing period. Rates of reactions fell during Years 1 and 2. When researchers looked at specifics details on the more severe reactions, most had occurred when kids exercised within two hours of their Palforzia dose. There were very few severe treatment-related reactions after Year 2.

The level of peanut-specific IgE antibodies also fell over time, from 84 kUA/L before treatment to 11.25 in Year 5. Meanwhile, skin test wheal diameters fell from an average of 11.5 millimeters to 5.75 in Year 5.

“Long-term treatment … demonstrated a decreasing frequency of adverse events,” and sustained changes to the immune system that indicate desensitization, Bird told the AAAAI meeting.