5 Questions: Kari Nadeau on advances in food allergy prevention and treatment

In the last decade, Stanford Medicine research has played a big role in advancing new therapies for food allergies in children and adults. Kari Nadeau, MD, PhD, professor of medicine and of pediatrics, spoke with science writer Erin Digitale about milestones in the field, including a newly approved drug for peanut allergy and a growing body of evidence that patients with several food allergies can be safely treated for all their allergies at once.

Nadeau, who directs the Sean N. Parker Center for Allergy and Asthma Research at Stanford University, co-wrote a book on food allergy that was published in September.

1. What do we know about the breadth and day-to-day impact of food allergies?

Nadeau: One in 12 children in the U.S., Europe, China, Korea and Japan have food allergies. Australia is higher, with 1 in 10. These are true doctors’ diagnoses of children who could go into potentially fatal anaphylactic shock from food. It really is a global epidemic.

And food allergy doesn’t always begin in childhood. Two years ago, our team published a study surveying 40,000 U.S. adults: About 1 in 10 had a food allergy. Surprisingly, 50% of them did not know this until they were adults.

Individuals with allergies must strictly avoid the problem food, maintaining vigilance about grocery store purchases, eating in restaurants, travel, social activities and so on. I think that, for many patients, the restrictions of the COVID-19 pandemic weren’t that big a change; they already lived in a state of anxiety about their safety.

2. Over the last 20 years, there was a revolution in recommendations for food allergy prevention. What happened?

Nadeau: In 2000, we told everyone to avoid possible allergens in early life — for instance, “Don’t feed your kid milk or egg until they’re 1 or 2 years old.” That recommendation came from well-meaning people, but unfortunately was not based on much data. They thought, “This epidemic of food allergies has been increasing since the 1940s, so let’s stop infants from eating these types of foods.”

Food allergies skyrocketed after those guidelines were introduced. And then some big studies came out, using data from several countries, on what it takes to prevent childhood allergies. Now we have a wealth of evidence saying the “5 Ds” are helpful: Make sure your vitamin D levels are good; if you can, keep a dog while your kids are small; have good dirt around; avoid dry skin and strong detergents that are hard on the skin; and diversify the diet early.

Our mantra now is “through the skin, allergies begin; through the diet, allergies stay quiet.” Food proteins that enter the body through breaks in the skin — such as if a baby has eczema — can trigger allergies, whereas new foods entering the gut at the right time, when solid foods are introduced, can help the body see them as safe.

Stanford patented a powdered food product that can be mixed with baby food, which exposes babies to a wide variety of food proteins to help prevent allergies. It’s now commercially available and being distributed globally.

3.  Your research has focused on using oral immunotherapy to treat food allergies. What are the big milestones in that work?

Nadeau: Oral immunotherapy had been around since the early 1900s. Patients get tiny, gradually escalating amounts of the food protein that triggers their allergy, under a doctor’s supervision. For instance, if you have egg allergy, we’ll give you small amounts of egg every day and gradually desensitize you. If you have a peanut allergy, we’ll give peanut. But if you have peanut and egg allergies, you would traditionally have had to be desensitized to one food at a time, which could take years. Studies have shown that over time, oral immunotherapy down-shifts the sensitivity of dendritic cells, immune cells at the center of the allergic response. They become less likely to trigger the events that characterize allergic reactions, including production of immunoglobin E antibodies.

I’m a mom and a pediatrician. When families asked me how to help their children who had multiple food allergies, I thought, “Let’s be practical: The body sees all allergens as protein. Our immune system doesn’t know what food it comes from.” So we started clinical trials to try desensitizing patients to multiple food allergens at once.

We found that it was very doable. We could desensitize patients to up to five allergens at a time. In nine months, with a medication called omalizumab that suppresses the immunoglobulin E immune response, we could get patients to tolerate up to two grams of protein, or a tablespoon of food, for each of their allergens: milk, eggs, shrimp, peanut, tree nuts and so on. It was just as safe as when we desensitized to one allergen at a time. We now have a Phase 3 trial underway that, if it meets its endpoint, will provide the evidence that allows people to get insurance coverage for this approach. So that’s exciting.

We have also studied biomarkers that predict when the treatment produces a cure: We’ve identified eight genes that can be tested for epigenetic changes to show if someone is cured, meaning they maintain tolerance to their allergens without eating them every day. The shift from “treated” to “cured” isn’t assured; some patients who have completed oral immunotherapy lose their tolerance to their allergens if they don’t eat them every day, while others do not.

4. For years, oral immunotherapy was available mainly through clinical trials, with little access outside academic medical centers. In January, Palforzia, the first drug for a food allergy, received approval from the Food and Drug Administration. The drug is an oral immunotherapy for peanut allergy. What’s your reaction to this change?

Nadeau: I’m a big supporter of FDA approval and making sure we can get insurance coverage for these therapies. That helps everyone to get treatment. We really need to make sure we fight for the underserved to maximize their access to food-allergy care, including access to epinephrine injection devices, which counteract anaphylactic shock when someone is accidentally exposed to a food allergen.

Of course, we still need people to enroll in clinical trials. There are so many open research questions: Can people live for decades after oral immunotherapy and still be cured? How do we stop the epidemic of food allergies? What are the reasons any one individual develops an allergy? I really appreciate the patients and families who volunteer for our clinical trials. They are heroes.

5. You’ve just co-written a book called The End of Food Allergy, which was published late last month. Why did you write this book?

Nadeau: We at Stanford had participated in the original Phase 1 study of the new peanut allergy drug, and I began thinking about how to share all the work done here and elsewhere, as well as the compelling stories from our patients.

Also, more people were asking me, “What’s causing the epidemic of food allergies? How can we prevent it?” I thought I could put that information in a book as a resource. I also noticed a lot of patients and families coming to me with inaccurate information from the internet. The book is thoroughly cited, with science to back up everything we say. It has a myth-buster section with citations of relevant research.

In addition, I wanted to make sure patients had a how-to book that was easy to read and compassionate toward their needs; that was useful for clinicians, with an array of resources to connect to; and that would help educate people without food allergies who need this information, such as teachers, coaches and grandparents.

We’re planning to set up an “End of Food Allergy” website so that people can continue to read about new discoveries in real time. I hope this will open the door to many more discussions.

Nadeau recently discussed food allergy in a 1:2:1 podcast with Paul Costello, senior communications strategist and adviser for Stanford Health Care and the School of Medicine.