Can This Treatment Cure a Peanut Allergy?

On a September morning in 2013, Edwin Kim, MD, gave his 9-month-old son, Elliot, a bit of peanut butter on a cracker. A minute later, a rash broke out over his baby’s entire body. Elliot began to cough, and then he vomited.

Dr. Kim rushed his son to the emergency room and realized this was what his patients’ families go through. As an allergist, Dr. Kim had heard parents tell their stories, and now he was in their shoes, frightened in the emergency department. His child was allergic to peanuts, just like many of the kids he sees at the UNC Allergy and Immunology Clinic and an estimated 1.6 million other kids in the United States.

A New Treatment for Peanut Allergies?

The day before he rushed Elliot to the hospital, Dr. Kim had been in his lab researching treatment methods to help kids overcome allergies to foods such as nuts, legumes and eggs.

“For the past 10 years, I’ve been trying to develop a therapy that can protect kids from the most severe allergic reactions,” says Dr. Kim, who is an assistant professor of medicine at the UNC School of Medicine and a member of the UNC Children’s Research Institute. “We’re less concerned that kids can’t eat peanut butter and jelly sandwiches; we just want to protect kids, including my own, from accidental exposures.”

The latest hope involves placing tiny drops of liquefied peanut protein under the tongue to immunize people against allergic reactions. Dr. Kim is a leader on this kind of therapy, called sublingual immunotherapy, or SLIT.

Here’s how it works: When under the tongue, the tiny peanut droplet is absorbed immediately, and immune cells recognize the protein. The amount is so small that the immune system does not overreact: In fact, there’s no, or very little, allergic reaction. Over time, a child’s immune system becomes desensitized to the peanut protein, as it’s slowly trained to not freak out when faced with larger amounts of peanut, which is what often happens in accidental exposures.

Results from Dr. Kim’s latest clinical trial were published in the Journal of Allergy and Clinical Immunology (JACI), and they show that SLIT could offer a safe and effective way to protect people from severe allergic reactions, even anaphylaxis.

“As a parent of a child with a peanut allergy and another with a cashew allergy, I know the fear parents face and the need for better treatments,” Dr. Kim says. “We now have the first long-term data showing that sublingual immunotherapy is safe and tolerable while offering a strong amount of protection.”

Types of Immunotherapy Treatment for Peanut Allergies

SLIT is the least known of three main immunotherapeutic techniques clinician scientists have created for people with peanut allergies. All of them attempt to desensitize the immune system to peanut proteins to help people avoid severe allergic reactions, which Dr. Kim says can be triggered by about 100 milligrams of peanut protein. That’s the sort of trace amount people fear can show up in food that’s “manufactured in a facility that processes peanuts,” as many food packaging labels say. For reference, one peanut kernel is about 300 milligrams.

“The main idea beyond immunotherapy is to keep kids safe from the small hidden exposures that could occur with packaged foods, at restaurants and with other food exposures,” Dr. Kim says.

The most well-known and well-studied immunotherapy method is called oral immunotherapy, which requires people to eat a small portion of peanut protein daily. Similar to SLIT, the amount is increased over time to desensitize the immune system.

“Some kids are not thrilled with ingesting peanut flour because of the taste, which they associate with a severe allergic reaction they may have had,” Dr. Kim says. “But some kids don’t mind at all, and parents can hide the taste in other food or drinks.”

In a large clinical trial, oral immunotherapy patients started with ingesting 0.5 milligrams of peanut, which was increased to 300 milligrams over many weeks before maintaining that amount every day for the remainder of a year. This trial showed substantial effectiveness in protecting people, but some had serious side effects. A subsequent analysis of oral immunotherapy data published in The Lancet in April suggested that more clinical research was needed because of the risk of serious side effects. Today, the Food and Drug Administration is reviewing oral immunotherapy.

The second kind of immunotherapy, which is also under FDA review, involves placing a small patch on the skin that releases a small amount of peanut protein to desensitize the immune system.

“This approach has proven to be safe in clinical research but perhaps not as effective as researchers had hoped,” Dr. Kim says. “Still, it could become an FDA-approved treatment.”

The third approach is SLIT, and it has some advantages over the previous types of immunotherapy. One is that kids don’t taste the tiny drop under the tongue. Another is that, unlike in oral immunotherapy, the peanut protein in the drop avoids the digestive tract, so it requires much smaller doses.

In 2011, Dr. Kim and colleagues, including Wesley Burks, MD, dean of the UNC School of Medicine, conducted a small study of 18 patients to show that SLIT was safe and effective over one year. Dr. Kim’s team started each child with just a 0.0002-milligram dose of liquefied peanut under the tongue. The researchers increased that amount to 2 milligrams over a few months.

Since 2011, Dr. Kim and colleagues have seen 48 patients in the SLIT protocol of 2 milligrams daily for five years. The results have been encouraging: In the 2019 JACI paper, the researchers showed that 67 percent of patients could tolerate at least 750 milligrams of peanut protein without serious side effects. About 25 percent could tolerate 5,000 milligrams.

The Future of Allergy Immunotherapy

Dr. Kim’s data show SLIT is about as effective as oral immunotherapy. Although the SLIT study was much smaller, he says the approach poses much less risk of serious side effects. (The most common side effect was itchiness around the mouth that lasted about 15 minutes and did not need treatment.) Additionally, no one left the multiyear SLIT study because of side effects, which cannot be said for oral immunotherapy trials.

“Our sublingual immunotherapy participants tolerated between 10 and 20 times more peanut protein than it would take for someone to get sick,” Dr. Kim says. “We think this provides a good cushion of protection; maybe not quite as good as oral immunotherapy, but with an easier mechanism (under the tongue) and, as far as we can tell right now, a better safety signal.”

Dr. Kim’s lab has finished a separate SLIT study of 4 milligrams daily for 55 patients over four years. He hopes to publish the results this year.

“With sublingual immunotherapy, we hope we can maintain our safety profile while seeing an even stronger benefit for patients,” Dr. Kim says.

Dr. Kim and colleagues are also studying SLIT in a subset of children ages 1 to 4 because data from oral immunotherapy studies have shown that young patients have a stronger, more lasting benefit from immunotherapy.

“In our clinic, we focus on the idea there is no one perfect drug for food allergy,” Dr. Kim says. “There will have to be a lot of shared decisions between physicians, patients and parents about what method of treatment is best for each person. But we’re confident sublingual immunotherapy could be a good option for a subset of people.”

For more information, contact the UNC Allergy and Immunology Clinic or the UNC Children’s Research Institute.