Calvin Hall is five years old and ready to attend school this year at Grass Valley Elementary. Like most five-year-old boys, he has certain food preferences: mac and cheese, cheeseburgers and pizza. He’d like to try the classic kids’ lunch peanut butter and jelly sandwich some time but right now he can’t because he’s severely allergic to peanut butter. In fact, if he eats one peanut he could go into anaphylactic shock.
His mother, Kaley Daniels-Hall, carries an Epi-pen with her everywhere and makes sure he has one with him when he goes to friends’ houses just in case a peanut strays into Calvin’s world. But she’s also hopeful that a potentially new exposure protocol will help ease her son’s severity.
Carefully calibrated doses of peanut protein can turn extreme allergies around. At the end of a year of slowly increasing exposure, most children who started off severely allergic could eat the equivalent of two peanuts.
That reversal, reported November 2018 in the New England Journal of Medicine (NEJM), “will be considered life-transforming for many families with a peanut allergy,” says pediatric allergist Michael Perkin of St. George’s, University of London, who wrote an accompanying editorial in the same issue of NEJM. The findings were also presented on the same day at the annual meeting of the American College of Allergy, Asthma and Immunology in Seattle.
Peanut exposure came in the form of a drug called AR101, described in the study as a “peanut-derived investigational biologic oral immunotherapy drug,” or, as Perkin puts it, “peanut flour in a capsule.” Unlike a sack of peanut flour, AR101 is carefully meted out, such that the smallest doses used in the study contained precisely 0.5 milligrams of peanut protein — the equivalent of about one six-hundredth of a large peanut.
In the clinical trial, 372 children ages 4 to 17 years began taking the lowest dose of AR101. The doses increased in peanut protein every two weeks until the kids topped out at 300 milligrams, which is about that of a single peanut.
Kids who are allergic to peanuts were given either a daily placebo or increasing doses of peanut protein for one year. Only 4 percent of children who received the placebo were able to tolerate 600 milligrams of peanut protein, or the equivalent of two large peanuts without bad reactions. Of those who completed a year of treatment, 67 percent could tolerate the equivalent of two large peanuts.
For the next 24 weeks, participants, located in the United States, Canada and Europe, took that dose daily. When the trial ended, all of the participants were challenged with increasing doses of peanut protein under close supervision. Two-thirds of the 372 children who received the peanut protein regimen, or 250 participants, could tolerate a peanut protein dose of at least 600 milligrams, comparable to about two peanuts. In contrast, only five of the 124 children who received placebos, or 4 percent, could tolerate the same dose. (A smaller number of adults ages 18 to 55 were enrolled in the study, but didn’t show big improvements.)
That improved tolerance “can really change the lives of patients who are peanut allergic,” says study coauthor Daniel Adelman, an allergist and immunologist at Aimmune Therapeutics, a company based in Brisbane, California, that makes AR101 and sponsored the trial.
During the study, nearly all of the participants who received the drug had allergic reactions to it — reactions that were expected, since “you’re giving people the thing they’re allergic to,” Adelman says. Most of those reactions weren’t severe, such as a rash or slight abdominal pain.
The goal of the treatment is not to cure the allergy or enable children to eat peanut butter sandwiches, but to reduce the risk that an accidental exposure to trace amounts will trigger a life-threatening reaction in someone with a severe allergy, and relieve the fear and anxiety that go along with severe peanut allergies.
“It isn’t a cure like an antibiotic that makes a bug go away and it’s not there anymore,” Perkin said. But “psychologically it makes a massive difference if you can keep your kid from living in fear. These kids can eat enough peanut that parents no longer will have to worry about their teenage daughter kissing someone who’s eaten peanut butter. You cannot estimate what a psychological relief that is.”
Although the drug is made of peanut protein, parents, or even doctors, shouldn’t attempt a similar treatment by measuring peanut protein themselves, experts say. Without exact measurements, peanut exposure could be dangerous. “This is treating peanut like a medicine, not a food,” says pediatric allergist Scott Sicherer of the Icahn School of Medicine at Mount Sinai in New York City. “Don’t try this at home.”
Schicher also cautions that, while the regimen is promising, it is not a cure. It’s not yet clear how long people would need consistent peanut protein exposure to maintain their tolerance, but regular use is probably needed. “It has to be a routine,” he says.